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Background Neoadjuvant chemotherapy (NCT) is considered more effective in downstaging hormone receptor-positive (HR+) breast cancer than neoadjuvant endocrine therapy (NET), particularly in node-positive disease. This study compared breast and axillary response and survival after NCT and NET in HR+ breast cancer. Methods Based on American College of Surgeons Oncology Group (ACOSOG) Z1031 criteria, women age 50 years or older with cT2-4 HR+ breast cancer who underwent NET or NCT and surgery were identified in the National Cancer Database 2010–2016. Chi-square and logistic regression analysis determined differences between the NCT and NET groups and therapy response, including downstaging and pathologic complete response (pCR, ypT0/is and ypN0). Results Of 19,829 patients, 14,025 (70.7%) received NCT and 5804 (29.3%) received NET. The NET patients were older (mean age, 68.9 vs. 60.3; P < 0.001) and had greater comorbidity (1+ Charlson–Deyo score, 21% vs. 16%; P < 0.001). Therapy achieved T downstaging (any) for 58% of the patients with NCT versus 40.5% of the patients with NET, and in-breast pCR was achieved for 9.3% of the NCT versus 1.3% of the NET patients (P < 0.001). Approximately half of the mastectomy procedures could have been potentially avoided for the patients with in-breast pCR (53.6% of the NCT and 43.8% of the NET patients). For the cN+ patients, N downstaging (any) was 29% for the NCT patients versus 18.3% for the NET patients (P < 0.001), and nodal pCR was achieved for 20.3% of the NCT versus 13.5% of the NET patients (P < 0.001). Among those with nodal pCR, axillary lymph node dissection (ALND) still was performed for 56% of the patients after NCT and 45% of the patients after NET. Conclusions Although the response rates after NCT were higher, NET achieved both T and N downstaging and pCR. Neoadjuvant endocrine therapy can be used to de-escalate surgery for patients who cannot tolerate NCT or when chemotherapy may not be effective based on genomic testing. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-021-10459-3.

Real-world data are critical to demonstrate the reproducibility of evidence and external generalizability of randomized clinical trials. Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6 that has been shown to improve progression-free survival (PFS) when combined with letrozole or fulvestrant in phase 3 clinical trials. We evaluated real-world outcomes in metastatic breast cancer patients who received palbociclib in combination with endocrine therapy in routine clinical practice. Records of patients with advanced hormone receptor (HR)-positive breast cancer treated with palbociclib at the Cleveland Clinic health system from February, 2015 to December, 2017 were retrospectively reviewed. The primary end point was PFS. In this cohort, 411 women were included. The median age and follow-up times were 53.5 years and 10.2 months, respectively. The median PFS for palbociclib plus letrozole was 15.1 months for patients treated in first line, 10.5 months in second line, and 4.2 months in third line and beyond. For patients who received fulvestrant plus palbociclib, the median PFS in first, second, and third line and beyond were 11.6, 12.3, and 6.4 months, respectively. The most common adverse events were hematologic, with grade 3–4 neutropenia occurring in 58% of patients. Thirty-one (8%) patients permanently discontinued palbociclib due to adverse events. Among patients with HR-positive advanced breast cancer, the estimated PFS in patients treated with fulvestrant and palbociclib was comparable to a previously reported phase 3 trial. However, the median PFS with letrozole and palbociclib was shorter than previously reported data from phase 2 and 3 trials. Palbociclib toxicity was very manageable, with a low drug discontinuation rate.

Background gpNMB is an internalizable transmembrane protein overexpressed in ˜40% of TNBC, and associated with a worse prognosis. Preclinical data implicates gpNMB in tumor invasion and metastasis. GV is a novel ADC designed to deliver monomethyl auristatin E (MMAE) to gpNMB-overexpressing cells. Prior phase 1/2 studies suggested promising activity of GV in gpNMB-overexpressing TNBC. Methods In the METRIC trial (NCT#01997333), patients (pts) with mTNBC were randomized 2:1 to GV (1.88 mg/kg IV q21 days) or capecitabine (2,500 mg/m2 PO daily d1-14 q21 days) until disease progression or intolerance. Key eligibility criteria included: gpNMB over-expression (>25% tumor cells positive by central immunohistochemistry of archival tissue); estrogen and progesterone receptor expression Results From Feb 2014 to Aug 2017, 327 women were randomized at 120 institutions to GV (n=218) or capecitabine (n=109). Pretreatment characteristics were well balanced between arms: median age of 55 years; 77% visceral disease; 2.4 years median duration of disease at study entry; 1 median prior anticancer regimen for metastatic disease. At the cut-off for final data analysis (Nov 30, 2017), 21 pts remained on treatment and 98 pts were alive. For GV vs. capecitabine based on independent central review, median PFS was 2.9 (95% CI: 2.8, 3.5) vs. 2.8 (95% CI: 1.6, 3.2) months (HR=0.95; p=0.76); median OS was 8.9 (95% CI: 7.9, 10.5) vs. 8.7 (95% CI: 6.9, 10.8) months (HR=1.06; p=0.73); ORR was 16% (95% CI: 11.1, 22.4) vs. 15% (95% CI: 8.6, 23.5); and median DOR was 5.6 (95% CI: 3.0, 7.8) vs. 4.2 (95% CI: 3.0, 12.2) months. A post-hoc subgroup analysis suggested the greatest benefit from GV was in potentially taxane-sensitive disease (i.e., not previously rechallenged or >6 months progression-free interval following last taxane). The incidence of grade ≥ 3 treatment-related adverse events (TRAEs) was 58% in the GV arm and 37% in the capecitabine arm. The most common grade ≥ 3 TRAEs were neutropenia (27%), rash (15%), and leukopenia (9%) in the GV arm, and diarrhea (14%) and palmar-plantar erythryodysesthesia (8%) in the capecitabine arm. There was 1 fatal TRAE of neutropenic sepsis in the GV arm and none in the capecitabine arm. Conclusion The METRIC study evaluating GV in mTNBC did not meet the primary efficacy endpoint of improved PFS over capecitabine. While anticancer activity was seen with GV, it was comparable to capecitabine with no therapeutic advantage of GV in terms of ORR, PFS, or OS. The safety profile of GV was consistent with prior experience with no new safety signals identified. Citation Format: Vahdat LT, Forero-Torres A, Schmid P, Blackwell K, Telli ML, Melisko M, Holgado E, Moebus V, Cortes J, Fehrenbacher L, Montero AJ, Ma C, Nanda R, Wright GS, He Y, Bagley RG, Halim A, Turner CD, Yardley DA. METRIC: A randomized international phase 2b study of the antibody-drug conjugate (ADC) glembatumumab vedotin (GV) in gpNMB-overexpressing, metastatic, triple-negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-20-01.

Poor lifestyle choices play a significant role in the development and progression of preventable chronic diseases, including cancer. In this study, we evaluate the effectiveness of a comprehensive lifestyle medicine intervention on chronic disease risk factors and quality of life in breast cancer survivors.This is a retrospective review of a clinical program from January 2016 to July 2017.It includes seven 2-h group medical visits held every other week at an outpatient wellness facility.Eligible participants are breast cancer survivors who have completed treatment, including those who remain on hormonal therapy.Patients receive education and experience in nutrition, culinary medicine, physical activity, and stress relief practices.Participants' weight, body mass index (BMI), body fat mass, lean body mass, and percent body fat were measured at visit 1 and visit 7. Standard validated questionnaires were used to measure perceived stress, depression, patient activation, physical and mental quality of life, dietary fat consumption, and dietary fruit, vegetable, and fiber consumption.A total of 31 patients participated in the group visits. Pre-post comparison data were not available for 10 patients. More than three-quarters of the 21 breast cancer survivors who attended 5 or more of the 7 group visits and provided data at the first and the last group visit decreased their body weight. On average, patients lost 4.9 pounds (-2.6%, p 0.01), and their BMI decreased by 0.8 kg/mBreast cancer survivors could employ the prescribed lifestyle modifications to produce clinically relevant health benefits. Interdisciplinary teams of health care professionals may help breast cancer survivors with chronic diseases implement evidence-based, individualized, and effective lifestyle prescription through group medical visits.

543 Background: Early validation studies using the Oncotype DX recurrence score (RS) in NSABP B20 demonstrated that women with node negative breast cancer and RS >31 had significant survival benefit from the addition of adjuvant chemotherapy to endocrine therapy (CET). Consequently, in the prospective TAILORx trial, node negative women with RS >26 received CET. These studies did not clearly delineate the magnitude of benefit of adjuvant chemotherapy for post-menopausal node negative women. A recently published well-designed adjuvant trial (RxPONDER) demonstrated that adjuvant chemotherapy was not beneficial in post-menopausal pts with ER+/HER2- breast cancer, 1-3 positive nodes, and RS 26 compared to endocrine therapy (ET) alone, given that CET is more beneficial in women 50 with ER+/HER2- pT1-2N0M0 breast cancer with RS >26, to assess real world utilization. We separated women into two groups based on adjuvant treatment: ET alone or CET. Chi-square and logistic regression analysis determined difference between different systemic treatment groups. OS was analyzed using a multivariable Cox model. Results: A total of 16,745 eligible women who underwent surgery and received ET were identified in the NCDB—4,740 (28.3%) received ET alone and 12,005 (71.7%) received CET. We observed that CET use increased over time. Women were more likely to receive CET if their tumors were moderately differentiated (OR = 1.853, p < 0.001), poorly/undifferentiated tumors (OR = 3.875, p < 0.001), or associated with lymph-vascular invasion (OR = 1.206, p = 0.001). After accounting for demographic and oncologic factors, 5-year OS rates in this cohort were significantly superior in women receiving CET compared to ET alone (95.4% vs 92.0%, Hazard Ratio = 0.680, p < 0.001). Conclusions: Utilizing the NCDB to represent real world outcomes, we observed that women > 50 years with pT1-2N0M0 ER+/HER2- breast cancer, and RS > 26 had a significantly superior 5-year OS when receiving adjuvant chemotherapy provides a measurable OS benefit for post-menopausal women in this setting and should be discussed with patients.

1100 Background: EMERALD demonstrated significantly prolonged progression-free survival (PFS) and a manageable toxicity profile for elacestrant vs standard of care endocrine therapy (SOC) in patients with ER+/HER2- mBC following progression on prior endocrine and CDK4/6 inhibitor therapy. Benefit was observed in the overall study population and in patients with ESR1 mutations (mESR1). Here, we report a subgroup analysis from EMERALD in patients with no prior chemotherapy. Methods: EMERALD (NCT03778931) is a randomized, open-label, phase 3 trial that enrolled patients with ER+/HER2− mBC who had 1–2 lines of endocrine therapy, mandatory pretreatment with a CDK4/6 inhibitor, and ≤1 chemotherapy. Patients were randomized 1:1 to elacestrant (400 mg orally daily) or SOC (investigator’s choice of fulvestrant or aromatase inhibitor). Primary endpoints were PFS in all patients and patients with mESR1. In this analysis, we compared PFS between elacestrant and SOC in patients without prior chemotherapy. Results: Among the 477 patients enrolled in the trial, 77.8% (n = 371) had not received prior chemotherapy for mBC (median age = 64). Among patients without prior chemotherapy, treatment with elacestrant was associated with significantly prolonged PFS compared to SOC in both the overall population (hazard ratio [HR] = 0.68 [95% CI, 0.52-0.89] P = 0.004; median PFS 3.7 vs 2.0; 6-mo PFS 38% vs 23%; 12-mo PFS 27% vs 12%), and patients with mESR1 (HR = 0.54 [95% CI, 0.36-0.80] P = 0.002; median PFS 5.3 vs 1.9; 6-mo PFS 44% vs 24%; 12-mo PFS 31% vs 12%). Key treatment-related adverse events (AEs) in the no prior chemotherapy elacestrant group were nausea (25.9%), fatigue (12.7%), and hot flush (11.1%). There were no treatment-related deaths in either group. Conclusions: Among patients with ER+/HER2− mBC without prior chemotherapy, elacestrant significantly prolonged PFS compared to SOC endocrine therapy and showed favorable outcomes in this subgroup. Clinical trial information: NCT03778931.

540 Background: Based on the results of the RxPonder trial, post-menopausal women over age 50 with estrogen receptor (ER)+ breast cancer, 1-3+ nodes, and a 21-gene Oncotype DX recurrence score (RS) score of 20 being associated with a significantly inferior overall survival (OS) (P value range: < 0.001-0.019). In women with RS of 20-25, CET was associated with a significant improvement in OS compared to ET alone, regardless of age (age < = 50: HR = 0.334, P = 0.002; age > 50: HR = 0.521, P = 0.019). Conclusions: Among women with ER+/HER2- breast cancer with 1–3 positive nodes, and RS of 20-25, in contrast to the RxPonder trial we observed that CET was associated with an OS benefit in women regardless of age.

TPS10618 Background: Coronavirus disease 2019 (COVID-19), caused by betacoronavirus SARS-CoV-2, is associated with an increased risk of severe infection or death in cancer patients compared to the general population. The CANVAX trial recently demonstrated that short term immune responses to SARS-CoV-2 vaccines are modestly impaired in patients with cancer— particularly those who receive myelosuppressive chemotherapy. Because little is known regarding longitudinal antibody or T-cell responses in cancer patients who receive cytotoxic chemotherapy or non-myelosuppressive targeted systemic therapy, the aim of this longitudinal study is to assess immune B and T cell responses to SARS-CoV-2 over a 12-month period in solid tumor patients who receive chemotherapy or non-immunosuppressive therapy compared to healthy individuals without cancer. Methods: This is an ongoing prospective non-interventional clinical trial (NCT05238467). Approximately 100 patients will be enrolled into three different arms. Accrual began in May 2021 and 37 patients have been enrolled. Eligible patients must not have prior COVID-19 infection < 6 months from study enrollment and have a diagnosis of a solid tumor (breast, genitourinary, or gastrointestinal cancers), who either: received myelosuppressive chemotherapy within 60 days prior to initial or booster COVID vaccination, or who started on chemotherapy within 30 to 60 days after the initial or booster COVID vaccination (Arm A); or received non-immunosuppressive treatments (Arm B); or have no history of cancer or prior history of cancer but beyond 12 months from completion of curative cancer treatment (Arm C, control cohort). Whole blood will be collected in accordance with standard operating procedures. Blood samples analyzed for the presence of antibodies against the major antigenic components of SARS-CoV-2 including the spike glycoprotein (S), receptor binding domain (R) and nucleocapsid phosphoprotein (N). Antibody levels will be quantified utilizing quantitative ELISA. T-cell responses will also be quantified. The primary endpoint is seroprotection rate with an antibody titer protective (1:40) at any point: baseline, 2, 6, and 12 months. The secondary endpoint is to evaluate differences in longitudinal immunological responses to SARS-CoV-2 over a 12-month period. The difference of the seroprotection rate among 3 cohorts of participants will be examined using chi-square test. Moreover, the effect of treatment (chemotherapy, endocrine, TKIs) on seroprotection will be estimated using multivariable logistic regression controlling the effects of confounders, such as age, gender and cancer type. COVID antibody titers measured over time (baseline, 8 weeks, 6, 9, 12 months after the second vaccination) will be analyzed using mixed-effect models. Clinical trial information: NCT05238467.

Background Radiotherapy is the recommended treatment after breast‐conserving surgery (BCS) for early‐stage breast cancer (BC). However, there is no clear evidence whether radiotherapy after BCS improves the survival of elderly women diagnosed with early‐stage hormone receptor‐positive (HR+) BC. The aim of this study was to investigate the survival benefit associated with radiotherapy plus hormonal therapy vs hormonal therapy alone after BCS for early‐stage HR+ BC patients. Methods Using the Surveillance, Epidemiology, and End Results linked with Medicare data, we identified elderly (65 years and older) women diagnosed with early‐stage HR+ BC (2006‐2011) who received hormonal therapy with or without radiotherapy after BCS. A log‐rank test, Cox proportional hazards models, and propensity score matching were used to estimate the overall survival (OS) benefit associated with radiotherapy after BCS. Results Of the 5688 patients, there were 303 deaths from any cause. One hundred and eighty‐five (61%) of these deaths occurred in the hormonal therapy group, and 118 (39%) deaths occurred in the radiotherapy plus hormonal therapy group. The mean survival time in the radiotherapy plus hormonal therapy group was 5.32 ± 1.86 years compared with 4.92 ± 1.86 years in the hormonal therapy group. Based on the adjusted and propensity score matching analysis, patients in the adjuvant radiotherapy group had a lower risk of death compared with those who did not receive radiotherapy. Radiotherapy plus hormonal therapy decreased the risk of death by 32%. The effect estimates were similar in the adjusted and matched cohorts. Conclusions Radiotherapy plus hormonal therapy resulted in a significant improvement in the OS of elderly women diagnosed with HR+ BC.

Importance Indoleamine 2,3-dioxygenase 1 (IDO1) causes tumor immune suppression. The IDO1 pathway inhibitor indoximod combined with a taxane in patients with ERBB2-negative metastatic breast cancer was tested in a prospective clinical trial. Objective To assess clinical outcomes in patients with ERBB2-negative metastatic breast cancer treated with indoximod plus a taxane. Design, setting, and participants This phase 2 double-blinded randomized 1:1 placebo-controlled clinical trial enrolled patients at multiple international centers from August 26, 2013, to January 25, 2016. Eligibility criteria included ERBB2-negative metastatic breast cancer, ability to receive taxane therapy, good performance status, normal organ function, no previous immunotherapy use, and no autoimmune disease. The study was discontinued in June 2017 because of lack of efficacy. Data analysis was performed from February 2019 to April 2020. Interventions A taxane (paclitaxel [80 mg/m2] weekly 3 weeks on, 1 week off, or docetaxel [75 mg/m2] every 3 weeks) plus placebo or indoximod (1200 mg) orally twice daily as first-line treatment. Main outcomes and measures The primary end point was progression-free survival (PFS); secondary end points were median overall survival, objective response rate, and toxic effects. A sample size of 154 patients would detect a hazard ratio of 0.64 with 1-sided α = .1 and β = .2 after 95 events. Archival tumor tissue was stained with immunohistochemistry for IDO1 expression as an exploratory analysis. Results Of 209 patients enrolled, 169 were randomized and 164 were treated (85 in the indoximod arm; 79 in the placebo arm). The median (range) age was 58 (29-85) years; 166 (98.2%) were female, and 135 (79.9%) were White. The objective response rate was 40% and 37%, respectively (indoximod vs placebo) (P = .74). The median (range) follow-up time was 17.4 (0.1-39.4) months. The median PFS was 6.8 months (95% CI, 4.8-8.9) in the indoximod arm and 9.5 months (95% CI, 7.8-11.2) in the placebo arm (hazard ratio, 1.2; 95% CI, 0.8-1.8). Differences between the experimental and placebo arms in median PFS (6.8 vs 9.5 months) and overall survival (19.5 vs 20.6 months) were not statistically significant. Grade 3 or greater treatment-emergent adverse events occurred in 60% of patients in both arms. Conclusions and relevance This randomized clinical trial found that, among patients with ERBB2-negative metastatic breast cancer, addition of indoximod to a taxane did not improve PFS compared with a taxane alone. Trial registration ClinicalTrials.gov Identifier: NCT01792050.

BACKGROUND: Interleukin-12 (IL-12) is a potent immunoregulatory cytokine that plays a key role in the crosstalk between innate (dendritic, macrophage, and natural killer) and adaptive (T and B) cells promoting anti-tumor immune responses. DNA plasmid-based IL-12 delivered to accessible tumors by intratumoral injection and electroporation (TAVO-EP) has been shown to induce activation of innate and adaptive tumor-infiltrating and peripheral immune cells, regression of treated and distant untreated lesions (abscopal effect), and expression of PD-L1 in patients with melanoma or triple-negative breast cancer (TNBC), without the systemic toxicity that has limited therapeutic use of IL-12 historically. The combination of TAVO-EP and pembrolizumab has demonstrated durable responses in melanoma patients with immunologically “cold” tumors or with prior progression on anti-PD1 therapy. Early clinical data indicate similar potential for eliciting strengthened immunogenic responses in TNBC. KEYNOTE-890 (OMS-I141) is a Phase 2 study in patients with metastatic TNBC to evaluate the safety and efficacy of TAVO-EP + pembrolizumab in the second-line or later (2L+) treatment setting (Cohort 1) or TAVO-EP + pembrolizumab + chemotherapy in the first-line (1L) setting (Cohort 2). Cohort 1 data are presented in a separate abstract. Enrollment in Cohort 2 is ongoing. METHODS: Cohort 2 of this Phase 2, open-label, multicenter study will be assessing the safety and efficacy of TAVO-EP in combination with pembrolizumab and chemotherapy as a first-line treatment for metastatic TNBC. Eligible patients are adults with metastatic TNBC (ER and PR staining Citation Format: Melinda Telli, Bianca Devitt, Katharine Cuff, Shaveta Vinayak, Rita Nanda, Alberto J. Montero, Rina Hui, David A. Canton, Christopher Twitty, Sunny Xie, Donna Bannavong, Bridget O'Keeffe, Sandra Aung, Rohit Joshi. Trial in progress: Phase 2 study of intratumoral plasmid interleukin-12 (tavokinogene telseplasmid; TAVO™) plus electroporation in combination with pembrolizumab with or without chemotherapy in patients with inoperable locally advanced or metastatic triple-negative breast cancer (KEYNOTE-890/OMS-I141) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-01-03.

Background: Endocrine therapy(ET) plus CDK4/6 inhibitor (i) is the mainstay for the management of estrogenreceptor-positive (ER+)/HER2- mBC. However, most patients (pts) with ER+ mBCeventually experience disease progression, including development of ESR1mutations (mESR1). Elacestrant, an oral SERD, demonstrated preclinical activity,and clinical activity in a phase 1 trial in ER+ mBC, including responses in ptswith prior fulvestrant, CDK4/6i, and mESR1tumors (Bardia JCO 2021).. Methods: EMERALD(NCT03778931), a multicenter, international, randomized, open-label, controlledphase 3 trial, enrolled postmenopausal pts with ER+/HER2- mBC who had received 1-2prior lines of ET and ≤1 line of chemotherapy in the mBC setting and had prior progressionon a ET plus CDK4/6i. Pts were randomized 1:1 to elacestrant (400 mg orallydaily) or standard of care (SOC; investigator’s choice of fulvestrant or anaromatase inhibitor). Stratification factors included mESR1 status (by central lab), priorfulvestrant exposure, and presence of visceral disease. The study had 2 primary endpoints of progression-free survival (PFS), by blindedindependent review committee, in pts withtumors harboring mESR1 and in all pts (mESR1 or mESR1 notdetected). Secondary endpoints included: overall survival (OS), safety, tolerability,and quality of life. An alpha-value of 0.0475 was used to determine statisticalsignificance (2-sided using the truncated Hochberg procedure).. Results: EMERALD enrolled 477 pts(228 with mESR1) between Feb 2019 - Oct 2020, with 239 pts randomized toreceive elacestrant vs 238 pts to SOC. Demographics and disease characteristicswere well-balanced across treatment arms [median age: 63 yrs vs 63.5 yrs; 2prior lines: 46% vs 40.8%; prior CDK4/6i: 100% in both arms]. The study met bothprimary endpoints. There was a 30% reduction in the risk of progression ordeath in the elacestrant arm in all pts (HR=0.697 [95% CI: 0.552, 0.88]; P=0.0018),and a 45% (HR=0.546 [95% CI: 0.387, 0.768]; P=0.0005) reduction in therisk of progression or death in pts with mESR1.For both endpoints, results in key prespecified subgroups, including visceral metastases,number of prior lines of therapy, pretreatment with fulvestrant, and geographicalregion, were consistent with the overall outcome. The PFS rate at 12 months was 22.32% (95% CI: 15.24%, 29.40%)with elacestrant vs 9.42% (95% CI: 4.02%, 14.81%) with SOC in all pts, and26.76% (95% CI: 16.17%, 37.36%) vs 8.19% (95% CI: 1.26%, 15.12%) in the mESR1 subgroup. The prespecified interim OS analysis plannedat the time of the final PFS analysis (allocated2-sided alpha level of 0.0001) demonstrated a trend in favor of elacestrant inall pts (HR=0.751 [95% CI: 0.542, 1.038]; P=0.0821) and in pts with mESR1(HR=0.592 [95% CI: 0.361, 0.958]; P=0.0325). The final OS analysisis expected next year. Common (>10%) treatment-related adverse events (AEs) withelacestrant vs SOC included: nausea (25.3% vs 8.7%), vomiting (11% vs 2.6%), and fatigue (11% vs 7.9%), mostlygrade 1/2. Treatment-emergent AEs leading to discontinuation of elacestrant orSOC were infrequent in both arms (6.3% and 4.4%). Grade ≥3 treatment-relatedAEs in the elacestrant arm vs SOC were 7.2% vs 3.1%, mainly driven by nausea(2.1% vs 0.9%). There were no treatment-related deaths in either group.. Conclusions:Elacestrant is the first oral SERD to demonstrate a statistically significantand clinically meaningful improvement of PFS vs SOC in a randomized phase 3study in pts with ER+/HER2- mBC in the 2nd/3rd-linesetting, including those whose tumors harbor mESR1. Elacestrant was well tolerated and hasthe potential to become the new standard of care for pts with ER+/HER2- mBC. Citation Format: Aditya Bardia, Patrick Neven, Guillermo Streich, Alberto J. Montero, Frédéric Forget, Marie-Ange Mouret-Reynier, Joo Hyuk Sohn, Peter Vuylsteke, Kathleen K. Harnden, Hung Khong, Judit Kocsis, Florence Dalenc, Virginia Kaklamani, Patrick Dillon, Sunil Babu, Simon Waters, Ines Deleu, José García-Sáenz, Emilio Bria, Marina Cazzaniga, Janice Lu, Philippe Aftimos, Javier Cortes, Shubin Liu, Dirk Laurent, Maureen G. Conlan, Francois-Clement Bidard. Elacestrant, an oral selective estrogen receptor degrader (SERD), vs investigator’s choice of endocrine monotherapy for ER+/HER2- advanced/metastatic breast cancer (mBC) following progression on prior endocrine and CDK4/6 inhibitor therapy: Results of EMERALD phase 3 trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS2-02.

Background CDK4/6 inhibitors (CDK4/6i), in combination with aromatase inhibitors, are United States Food and Drug Administration-approved for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). The effectiveness of continuing them beyond first disease progression (PD) is currently unknown. This retrospective study evaluated the impact of the continuation of CDK4/6i beyond first PD in HR+/HER2− MBC using real-world experience. Patients and Methods A single-institution retrospective review of patients with HR+ MBC who received CDK4/6is from 2015 to 2018 and where CDK4/6is were continued beyond first PD. The primary outcome was progression-free survival (PFS) after initial PD on CDK4/6i therapy. Results Thirty women with HR+/HER2− MBC met eligibility criteria. Patients were identified from a prospective database of patients at the Cleveland Clinic Foundation who were prescribed CDK4/6is. The median age and follow-up duration were 47.5 years and 27 months, respectively. Most patients received palbociclib (PA)/letrozole as initial therapy (67%), followed by PA/fulvestrant (23%), and PA/other aromatase inhibitor (20%), and abemaciclib with either fulvestrant or letrozole (6%). As of January 31, 2019, 25 (83.3%) patients were still alive, and 19 (63%) patients had progressed. The estimated median PFS for continued CDK4/6i use beyond the first PD was 11.8 months (95% confidence interval, 5.34-13.13 months). Conclusions Among a small cohort of patients with HR+ MBC in a non-clinical trial setting, continuation of CDK4/6i-endocrine treatment post initial PD was associated with a median PFS of about 12 months. Formal randomized clinical trials evaluating the continuation of CDK4/6is beyond the first PD are currently ongoing and will provide more answers to this important clinical question.

584 Background: Approximately 30% of all breast cancers are characterized as triple-negative (TNBC). TNBC typically occurs in younger women and is associated with a poorer prognosis relative to other breast cancer subtypes. High levels of tumor-infiltrating lymphocytes (TILs) in residual disease after Neoadjuvant chemotherapy (NACT) have previously been shown to be associated with better prognosis in TNBC. In this work, we sought to evaluate the prognostic value of computationally derived measures of TIL spatial architecture in residual TNBC after NACT. Methods: H&E-stained samples from 92 patients (pts) with TNBC (41 died, 45 had disease recurrence) and residual disease after NACT were retrospectively collected from 2 sites: Instituto Nacional de Enfermedades Neoplásicas (S1) and University Hospitals (S2). 45 pts (16 deaths, 23 recurrences) from S1 formed the training set and 47 pts (25 deaths, 22 recurrences) from S2 formed the independent validation cohort. Samples were digitized at 20x. Computerized algorithms automatically identified 2 types of nuclei (TILs and non-TILs) and built clusters for each nuclei type based on cell proximity. The spatial arrangement of these clusters was then quantified using network graph metrics. The top 5 features, determined by least absolute shrinkage and selection operator, were used to train a Cox regression model that assigned a risk of death and recurrence to each patient on the training set. The percentile 33 risk score was used as a threshold for stratifying pts on the validation set as either low or high risk. For comparison, we also employed a model based on TIL density alone. Survival analysis was used to evaluate the performance of both approaches on disease-free survival (DFS) and overall survival (OS). Results: Pts in S2 (n=47) identified as “high risk” by the model based on spatial architecture of residual TILs had a significantly shorter survival time. The median OS for pts at high risk was 25 months vs. 55 months for low-risk pts. The median DFS for pts at high risk was 32 months vs 51 months for low-risk pts. Univariable analysis showed this model was prognostic for both OS (Hazard Ratio (HR) = 2.57, 95% Confidence Interval (CI): 1.07-6.16, p=0.03) and DFS (HR=2.38, CI: 1.01-5.62, p=0.04). In contrast, the model based on TIL density was not prognostic for OS (HR=1.24, CI: 0.33-4.63, p=0.73) nor DFS (HR=1.19, CI: 0.32-4.34, p=0.78). Conclusions: A computerized image analysis model based on measurements of spatial arrangement of residual TILs and surrounding cells was found to be prognostic in TNBC pts who received NACT. This method appears to be more prognostic than TIL density alone. Additional multisite validation and multivariable analysis is needed to further establish the independent prognostic utility of TIL based image biomarkers in the post-NACT TNBC.

In 1996, Jim Allison demonstrated that blocking the immune regulatory molecule CTLA-4 with anit-CTLA4 antibody led to enhance tumor responses in mice. It would take an additional 15 years for human studies to confirm the potency and clinical efficacy of anti-CTLA4, ultimately leading to US FDA approval of the first checkpoint inhibitor, ipilimumab. Now with a plethora of immune-modulating agents demonstrating single agent safety and benefit across many tumor types, investigation on the optimal combination of immune-based therapies has begun in earnest. While there are many challenges, a central one is how to select which combination for which patient is the best. Here we review the current approaches that a practitioner can use to achieve this therapeutic goal.

Genomic profiling can identify targetable mutations; however, the impact of tissue-based genomic profiling on clinical decision making for patients with metastatic breast cancer has not been well characterized. Patients with stage IV breast cancer who had undergone genomic profiling between 7/2013 and 3/2015 were identified at three academic cancer centers. Genomic analysis was determined to have impacted clinical decision if (A) a patient was enrolled onto a genotype-matched clinical trial or (B) prescribed off-label an FDA-approved therapy targeting an identified mutation. The frequency of mutated genes was determined. A total of 117 patients with stage IV breast cancer were identified. Median age was 46 (25–75). Fifty-three patients (45%) had ER-positive/HER2-negative disease, 50 (43%) had ER-negative/HER2-negative disease, and 14 (12%) had ER-any/HER2-positive disease. Median number of previous therapies received prior to genomic profiling was 2 (range 0–15), and median follow-up after testing was obtained after 5.8 months (range 0–24.4 months). Commercial reports indicated that 85 (73%) patients had at least one mutation targetable by an FDA-approved medication, and 112 (96%) patients had at least one clinical trial available; however, clinical management was only affected in 11 patients (9%). The most frequent mutations observed were those in TP53, FGF, PI3KCA, MYC, ZNF, FGFR, CCND, ARID1A, GATA3, and MAP; frequencies of these mutations varied by clinical subtype. Tumor genomic profiling affected clinical management in a minority of patients with metastatic breast cancer, thus these data do not support the routine use of genomic profiling outside of a clinical trial.

Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration–approved immune checkpoint inhibitors—pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI)—demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma. Materials and Methods We developed Markov models by using a US-payer perspective and lifetime horizon to estimate costs (2016 US$) and quality-adjusted life years (QALYs) for treatment sequences with first-line NIVO, IPI, NIVO + IPI, PEM every 2 weeks, and PEM every 3 weeks. Health states were defined for initial treatment, first and second progression, and death. Rates for drug discontinuation, frequency of adverse events, disease progression, and death obtained from randomized phase III trials were used to determine the likelihood of transition between states. Deterministic and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. Results PEM every 3 weeks followed by second-line IPI was both more effective and less costly than dacarbazine followed by IPI then NIVO, or IPI followed by NIVO. Compared with the first-line dacarbazine treatment strategy, NIVO followed by IPI produced an incremental cost effectiveness ratio of $90,871/QALY, and first-line NIVO + IPI followed by carboplatin plus paclitaxel chemotherapy produced an incremental cost effectiveness ratio of $198,867/QALY. Conclusion For patients with treatment-naive BRAF wild-type advanced melanoma, first-line PEM every 3 weeks followed by second-line IPI or first-line NIVO followed by second-line IPI are the most cost-effective, immune-based treatment strategies for metastatic melanoma.

Background Venous thromboembolism (VTE) complicates several anticancer regimens including chemotherapy and antiangiogenic agents. Cyclin-dependent kinase inhibitors (CDKIs) are a new approach for hormone receptor-positive metastatic breast cancer (mBC). Reported VTE rates in randomized trials range from 0.6% to 5%, but these may underestimate actual rates observed in clinical practice. Objectives Evaluate VTE rate and its association with outcomes in CDKIs patients. Patients/methods We conducted a retrospective cohort study of consecutive mBC patients who received any of three Food and Drug Administration (FDA)-approved CDKIs (palbociclib, ribociclib, abemaciclib) from January 2015 through December 2017. Venous thromboembolism including deep venous thrombosis (DVT), pulmonary embolism (PE), and visceral vein thrombosis (VVT) were identified by electronic medical record review. Overall survival (OS) and progression-free survival (PFS) were estimated and evaluated for association with VTE using Cox proportional hazard regression. Results We included 424 patients, with a median age at diagnosis of 55 years. Palbociclib was the most commonly used CDKI (n = 390, 91.8%). Venous thromboembolism during CDKIs occurred in 38 patients, 6.3% at year 1, including DVT in 52.6%, PE in 18.5%, and VVT in 15.8%. Median time to VTE was 314 days. Venous thromboembolism was associated with a trend to worse PFS and OS in multivariate analysis [PFS hazard ratio (HR) 1.40, 95% confidence interval (CI) 0.83-2.38, P = .21], OS (HR 1.70, 95% CI 0.95-2.98, P = .076). Conclusions Venous thromboembolism rates with CDKI treatment in mBC in clinical practice are 2-fold to 5-fold greater than reported in registration trials and may be associated with worse outcomes.

Optimal ex vivo expansion protocols for adoptive cell therapy (ACT) must yield T cells able to effectively home to tumors and survive the inhospitable conditions of the tumor microenvironment (TME), while simultaneously exerting persistent anti-tumor effector functions. Our previous work has shown that ex vivo activation in the presence of IL-12 can induce optimal expansion of murine CD8(+) T cells, thus resulting in significant tumor regression after ACT mostly via sustained secretion of IFN-γ. In this report we further elucidate the mechanism of this potency, showing that IL-12 additionally counteracts the negative regulatory effects of autocrine IFN-γ. IL-12 not only downregulates PD-1 expression by T cells, thus minimizing the effects of IFN-γ-induced PD-L1 upregulation by tumor stromal cells, but also inhibits IFNγR2 expression, thereby protecting T cells from IFN-γ-induced cell death. Thus, the enhanced anti-tumor activity of CD8(+) T cells expanded ex vivo in the presence of IL-12 is due not only to the ability of IL-12-stimulated cells to secrete sustained levels of IFN-γ, but also to the additional capacity of IL-12 to counter the negative regulatory effects of autocrine IFN-γ.

Based on available phase III trial data, we performed a cost-effectiveness analysis of different treatment strategies that can be used in patients with newly diagnosed HER2-positive metastatic breast cancer (mBC).We constructed a Markov model to assess the cost-effectiveness of four different HER2 targeted treatment sequences in patients with HER2-positive mBC treated in the U.S. The model followed patients weekly over their remaining life expectancies. Health states considered were progression-free survival (PFS) 1st to 3rd lines, and death. Transitional probabilities were based on published phase III trials. Cost data (2015 US dollars) were captured from the U.S. Centers for Medicare and Medicaid Services (CMS) drug payment table and physician fee schedule. Health utility data were extracted from published studies. The outcomes considered were PFS, OS, costs, QALYs, the incremental cost per QALY gained ratio, and the net monetary benefit. Deterministic and probabilistic sensitivity analyses assessed the uncertainty around key model parameters and their joint impact on the base-case results.The combination of trastuzumab, pertuzumab, and docetaxel (THP) as first-line therapy, trastuzumab emtansine (T-DM1) as second-line therapy, and lapatinib/capecitabine third-line resulted in 1.81 QALYs, at a cost of $335,231.35. The combination of trastuzumab/docetaxel as first line without subsequent T-DM1 or pertuzumab yielded 1.41 QALYs, at a cost of $175,240.69. The least clinically effective sequence (1.27 QALYs), but most cost-effective at a total cost of $149,250.19, was trastuzumab/docetaxel as first-line therapy, T-DM1 as second-line therapy, and trastuzumab/lapatinib as third-line therapy.Our results suggest that THP as first-line therapy, followed by T-DM1 as second-line therapy, would require at least a 50 % reduction in the total drug acquisition cost for it to be considered a cost-effective strategy.

Five-year survival rates have improved over the past 40 years for nearly all types of cancer, partially thanks to early detection and prevention. Since patients typically present to their primary care physician with initial symptoms, it is vital for primary care physicians to accurately diagnose common cancers and to recognize unusual presentations of highly curable cancers such as Hodgkin lymphoma and testicular cancers, for which the 5-year overall survival rates are greater than 85%. This paper reviews these cancers and provides clinically relevant pearls from an oncologic perspective for physicians who are the first point of contact.

Background The objective of this study is twofold: 1) to propose a simulation model for HER2+ metastatic breast cancer (mBC) which could further be used to assess the overall cost-effectiveness of the treatment sequences that would maximize survival of patients, and 2) to estimate transitional probabilities between treatment lines required to parameterize the simulation model, in the absence of individual patient data (IPD). Methods Individual patient data (IPD) were reconstructed for treatment lines composing four treatment sequences. Parametric models were tested to select the model that best fits the IPD. The transitional probability equations, used for disease progression modeling, were obtained by substituting the parameters of the general equation for transitional probabilities by the parameters estimated from fitted distributions. Results The log-logistic model best fitted the reconstructed data for progression-free and overall survival curves for each line of treatment. The shapes and scales of the log-logistic models were used to develop the transitional probability equations for the HER2+ mBC simulation model.The estimation of the transitional probabilities depends heavily on the accuracy of the IPD reconstruction. Nonetheless, analytical and graphical tests can be performed to check the face validity of the reconstructed data. Additionally, sensitivity analyses can be conducted to test the impact of uncertainty surrounding the estimated parameters defining equations for transitional probabilities. Conclusion The results of this study can be used as input in model-based economic evaluations of sequential therapy for HER2+ mBC.

Background: Indoleamine 2,3 dioxygenase (IDO) is a tryptophan-catabolizing enzyme that plays a key role in the normal regulation of peripheral immune tolerance. Tumors also employ this mechanism to induce a state of immunosuppression, evading immune mediated destruction. Indoximod (D-1-methyltryptophan) is a broad IDO pathway inhibitor as it has been shown to potentially interfere with multiple targets within the IDO pathway. Preclinical studies in MMTV-neu mouse models have demonstrated that combining indoximod with cytotoxic chemotherapy had a greater in-vivo anti-tumor effect than either agent alone. A phase 1 trial combining docetaxel and indoximod demonstrated safety and responses in metastatic breast cancer (mBC) patients. Based on these data a phase 2 trial evaluating indoximod in combination with taxane chemotherapy as first line therapy in patients with metastatic breast cancer was initiated. Methods: The study is a 1:1 randomized, placebo controlled, four arm phase 2 trial. The study treatment is docetaxel 75mg/m2 IV D8 plus indoximod 1200mg PO BID D1-14 every 21 days or matching placebo in study arms 1A and 2A or paclitaxel 80 mg/m2 IV weekly 3 out of 4 weeks with indoximod or matching placebo given BID Days 1-14 in arms 1B and 2B. The primary endpoint is progression free survival. Secondary endpoints include overall survival, response rate, safety, and immune response correlative assays. Patients with measurable, histologically confirmed mBC, no prior chemotherapies (hormonal therapies allowed) in the metastatic setting, ER+ or ER –, HER2 -, ECOG PS 0-1, no active CNS disease, no active autoimmune disease are eligible. Target enrollment is 154 patients. Results: At submission, 65 patients have evaluable safety data on trial. The pooled, blinded data was evaluated for any safety signals. Patient demographics include median age 58 years, 95% female, 17% African American, 25% triple-negative disease, and 82% with multiple sites of metastatic disease. 28% of patients had at least one Grade 3 or 4 adverse event. Those occurring in multiple patients include dyspnea 5%, pleural effusion 3%, non-cardiac chest pain 3%, and febrile neutropenia 3%. Most patients had at least one adverse event (86%). The most common were anemia 14%, tearing 11%, constipation 19%, diarrhea34%, nausea 44%, vomiting 22%, fatigue 48%, peripheral edema 17%, increased liver function tests 10%, lymphopenia 17%, hyperglycemia 15%, myalgia 14%, dizziness 14%, dysguesia 16%, headache 20%, peripheral neuropathy 12%, dyspnea 19%, alopecia 34%, and rash 14%, all compatible with the side effect profile of single agent taxanes. No immune specific serious advents were reported. No treatment related deaths have been reported. Conclusion: The aggregate safety data for these 65 patient are similar to what is typically observed with docetaxel and paclitaxel. No unexpected serious immune linked adverse events were reported. The trial is currently open at multiple clinical sites in the US and Europe and actively enrolling patients. Updated data will be presented. NCT01191216. Citation Format: Tang S-C, Montero A, Munn D, Link C, Vahanian N, Kennedy E, Soliman H. A phase 2 randomized trial of the IDO pathway inhibitor indoximod in combination with taxane based chemotherapy for metastatic breast cancer: Preliminary data. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-11-09.

7057 Background: Cancer patients (pts) are at high risk of unplanned hospital readmissions. Predicting which cancer patients are at higher risk of readmission would improve post-discharge follow-up/navigation, decrease cost, and improve pt outcomes. Methods: We conducted a retrospective cohort study of non-surgical cancer pts hospitalized at our center between 12/2014 to 7/2018. A machine learning algorithm was trained on 348 medical, sociodemographic and cancer-specific variables with a total of 1,801,944 data points. The cohort was randomly divided into training (80%) and validation (20%) subsets. Prediction performance was measured by area under the receiver operator characteristic curve (AUC). Results: A total of 5,178 hospitalizations were included, of which 45.1% were women, and 27.6% experienced an unplanned readmission within 30 days. The most frequently represented cancers were hematologic malignancies (30.5%), followed by GI (18.1%), lung (13.7%), and GU (10.9%). Significant variables that impacted the algorithm decision are ranked from the most to the least important, including: days from last admission; planned index chemotherapy admission; number of vascular access lines, drains, and airways in use; length of stay; cancer diagnosis; total ED visits in past 6 months; age; discharge lab values (sodium, albumin, alkaline phosphatase, bilirubin, platelets); number of prior admissions; and discharge disposition. The AUC for the validation subset was 0.80. To ease the translation of this model into the clinic, we developed a web application whereby users can supply the aforementioned variables to the model and receive a personalized prediction that highlights those variables most affecting a subject’s readmission risk status: www.Cancer-Readmission.com. Conclusions: A cancer-specific readmission risk model with high AUC for 30-days unplanned readmission has been developed. The model is embedded in a freely available web application that provides personalized, patient-specific predictions. Programs that integrate this model can identify cancer patients with a greater risk for unplanned hospital readmission, thus providing a personalized approach to prevent future unplanned readmissions.

Breast cancer is a global health concern. In fact, breast cancer is the primary cause of death among women worldwide and constitutes the most expensive malignancy to treat. As health care resources are finite, decisions regarding the adoption and coverage of breast cancer treatments are increasingly being based on "value for money," i.e., cost-effectiveness. As the evidence about the cost-effectiveness of breast cancer treatments is abundant, therefore difficult to navigate, systematic reviews of published systematic reviews offer the advantage of bringing together the results of separate systematic reviews in a single report. As a consequence, this paper presents an overview of systematic reviews of the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer to inform policy and reimbursement decision-making. A systematic review was conducted of published systematic reviews documenting cost-effectiveness analyses of breast cancer treatments from 2000 to 2014. Systematic reviews identified through a literature search of health and economic databases were independently assessed against inclusion and exclusion criteria. Systematic reviews of original evaluations were included only if they targeted breast cancer patients and specific breast cancer treatments (hormone therapy, chemotherapy, and targeted therapy only), documented incremental cost-effectiveness ratios, and were reported in the English language. The search strategy used a combination of these key words: "breast cancer," "systematic review/meta-analysis," and "cost-effectiveness/economics." Data were extracted using predefined extraction forms and qualitatively appraised using the assessment of multiple systematic reviews (AMSTAR) tool. The literature search resulted in 511 bibliographic records, of which ten met our inclusion criteria. Five reviews were conducted in the early-stage breast cancer setting and five reviews in the metastatic setting. In early-stage breast cancer, evidence about trastuzumab value differed by age. Trastuzumab was cost-effective only in women with HER2-positive breast cancer younger than 65 years and over a life-time horizon. The cost-effectiveness of trastuzumab in HER2-positive metastatic breast cancer yielded conflicting results. The same conclusions were reached in comparisons between vinorelbine and taxanes. In both early stage and advanced/metastatic breast cancer, newer aromatase inhibitors (AIs) have proved cost-effective compared to older treatments. This overview of systematic reviews shows that there is heterogeneity in the evidence concerning the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer. The cost-effectiveness of these treatments depends not only on the comparators but the context, i.e., adjuvant or metastatic setting, subtype of patient population, and perspective adopted. Decisions involving the cost-effectiveness of breast cancer treatments could be made easier and more transparent by better harmonizing the reporting of economic evaluations assessing the value of these treatments.

Vitamin D (VD) supplementation has pleiotropic effects that extend beyond their impact on bone health, including the disruption of human epidermal growth factor receptor 2 (HER2) signaling through the ErbB2/AKT/ ERK pathway. We performed a retrospective review of patients who received VD supplementation during neoadjuvant chemotherapy (n [ 134) and those who did not (n [ 112). In our final multivariate model, VD use was associated with improved disease-free survival (DFS) (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.15-0.88); P [ .026). To the best of our knowledge, our study is the first to report a significant improvement in DFS for patients who received VD supplementation concurrently with trastuzumab-based chemotherapy for HER2-positive (HER2 D ) nonmetastatic breast cancer. Background: Vitamin D (VD) supplementation has pleiotropic effects that extend beyond their impact on bone health, including the disruption of downstream VD receptor signaling and human epidermal growth factor receptor 2 (HER2) signaling through the ErbB2/AKT/ERK pathway. In the present study, we examined our institutional experience with patients having nonmetastatic HER2-positive (HER þ ) breast cancer and hypothesized that those patients who received VD supplementation during neoadjuvant chemotherapy would have improved long-term outcomes. Patients and Methods: We performed a retrospective review of all patients (n ¼ 308) given trastuzumab-based chemotherapy between 2006 and 2012 at the University of Miami/Sylvester Comprehensive Cancer Center (UM/SCCC). We identified 2 groups of patients for comparison—those who received VD supplementation during neoadjuvant chemotherapy (n ¼ 134) and those who did not (n ¼ 112). Univariate and multivariate Cox proportional hazard regression models were fitted to overall survival (OS) and disease-free survival (DFS). Results: More than half of the patients received VD during neoadjuvant chemotherapy (54.5%), with 60% receiving a dose < 10,000 units/wk and 33.3% having aV D deficiency at the start of therapy. In our final multivariate model, VD use was associated with improved DFS (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.15-0.88; P ¼ .026], whereas larger tumor size was associated with worse DFS (HR, 3.52; 95% CI, 1.06-11.66; P ¼ .04). There were no differences in OS based on any of

Background Glycoprotein NMB (gpNMB) is an internalizable transmembrane protein overexpressed in approximately 20% of breast cancer (BC), including approximately 40% of TNBC. gpNMB is a poor prognostic marker in BC (Rose CCR 2010) and preclinically has been implicated in tumor invasion, metastasis, and angiogenesis. GV is a novel antibody-drug conjugate targeting the potent cytotoxin monomethylauristatin E (MMAE) to gpNMB overexpressing cancer cells. In a Phase I/II study and the Phase II "EMERGE" study, GV demonstrated promising activity with TNBC patients (pts) deriving the greatest benefit and exhibiting the highest degree of gpNMB overexpression. GV was well-tolerated with the most frequent treatment-related toxicities consisting of rash, neutropenia, and neuropathy. In subset analyses of the EMERGE trial, objective response rate (ORR) was 30% (7/23) for GV vs. 9% (1/11) for investigator's choice in tumors with gpNMB overexpression (>25% of tumor epithelium); 18% (5/28) vs. 0% (0/11) in TNBC; and 40% (4/10) vs. 0% (0/6) in gpNMB-overexpressing TNBC for GV and IC respectively, with apparent improvements in progression-free survival (PFS; hazard ratio (HR) = 0.11) and overall survival (OS; HR = 0.14). Trial design The METRIC Trial (NCT#01997333) is an international (USA, CA, Aus), two-arm phase II study. Pts are randomized 2:1 to GV (1.88 mg/kg IV q 21 days) or capecitabine, a current standard of care for this population (2,500 mg/m2 daily for d1-14, q21 days) until progression or intolerance. Crossover is not permitted. Eligibility criteria Key eligibility criteria include: >25% of tumor epithelium gpNMB+ by central immunohistochemistry (IHC) screening of archival tissue; estrogen receptor and progesterone receptor 2 toxicity. Specific aims The primary endpoint is PFS per independent, blinded central review committee according to RECIST 1.1. Secondary endpoints are ORR, duration of response, OS, safety, pharmacokinetics and pharmacodynamics. Exploratory endpoints are quality of life and/or cancer-related pain. Statistical methods and target accrual The trial has 85% power to detect a PFS HR of 0.64 with two sided α = 0.05. The hypothesized median PFS is 4.0 months for capecitabine and 6.25 months for GV. Target accrual is open for 300 pts. Citation Format: Melisko M, Yardley DA, Blackwell K, Forero A, Ma C, Montero A, Daniel BR, Wright G, Fehrenbacher L, Chew H, Ferrario C, Nanda R, Seiler Jr M, Guthrie T, Vance K, Ouellette G, He Y, Bagley RG, Zhang J, Vahdat LT. The METRIC trial: A randomized international study of the antibody-drug conjugate glembatumumab vedotin (GV or CDX-011) in patients with metastatic gpNMB-overexpressing triple-negative breast cancer (TNBC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-03-15.

Purpose: Hospital transfers may affect clinical outcomes. Evaluation of admission by source of transfer, time of admission, and provider type may identify opportunities to improve inpatient outcomes. Methods: We reviewed charts of patients admitted to the solid tumor oncology service between July and December 2014 from the Cleveland Clinic Foundation (CCF) Main Campus emergency department (ED), CCF Regional EDs, outside hospital (OSH) ED, OSH inpatient services, and CCF outpatient clinics. Data collected included time of admission, mortality and severity risk scores, and provider type. Risk factors were assessed for clinical outcomes, including activations of the Adult Medical Emergency Team, intensive care unit transfers, in-hospital mortality, and length of stay (LOS). Results: Five hundred admissions were included. OSH inpatient transfers had significantly higher disease severity compared with all other origins of admission. OSH inpatient transfers demonstrated significantly longer LOS compared with all other origins of admission, and higher mortality rates compared with the outpatient direct admits and CCF Main Campus ED admits. After adjusting for disease severity and risk of mortality, OSH ED patients remained at higher risk for Adult Medical Emergency Team activation, OSH inpatient transfers had the longest LOS, and CCF Main Campus ED patients had the lowest risk of mortality. Time of admission and provider type were not associated with any of the outcomes. Conclusion: Oncology inpatients transferred from an outside health care facility are at higher risk for adverse outcomes. The magnitude of difference is lessened, but still significant, after adjustment for disease severity and risk of mortality.

Purpose: Neutropenic fever (NF) is an oncologic emergency and has resulted historically in inpatient management. The Multinational Association for Supportive Care in Cancer (MASCC) score can be used to identify patients with NF at a low risk of complications who can be managed safely as outpatients. Despite established guidelines supporting outpatient management of low-risk neutropenic fever (LRNF), provider awareness is low, and inpatient admission for intravenous antibiotics continues to be standard of care. Methods: Inpatient provider algorithm implementation and education began in the second quarter of 2014. Providers calculated MASCC scores for patients with nonleukemia hematologic malignancies and solid tumors at admission. Data were collected in a prospectively maintained registry. Patients identified as low risk by MASCC score were placed under observation and started on oral antibiotics. If exclusion criteria and social barriers were not identified, discharge within 48 hours was planned. Results: Eighty-three patients with NF were admitted to the Taussig Cancer Institute inpatient oncology unit between November 2014 and June 2015. Fifty-three patients (64%) had LRNF by MASCC score. Patients with LRNF had an average length of stay of 3.3 days, compared with 6.2 days in our historical cohort. Sixteen patients (30%) were discharged within 24 hours. Only two patients with LRNF had a culture-proven infection, both Enterococcus urinary tract infections. Three patients required nonelective readmission. There were no deaths caused by NF. Conclusion: This pilot study demonstrates that a formal algorithm for LRNF management combined with provider education can improve current inpatient standard of care and length of stay without an increase in morbidity.

To determine if a low fixed dosing strategy of capecitabine would produce comparable clinical activity with less adverse toxicities compared to published data with higher doses in the setting of metastatic breast cancer (mBC). We retrospectively analyzed patients treated with a low fixed dose of capecitabine (CAPE-L) at 1,000 mg twice daily for 14 days every 21 days. Outcomes included clinical benefit rate (CBR), overall response rates (ORR), time to progression (TTP), and overall survival (OS). A historical comparison group of mBC patients treated on 12 prior trials at the package-insert dose of capecitabine (n = 1,949) was utilized. Eighty-six patients were analyzed in our cohort. Positive hormone receptor status (79.1 vs. 50.6 %), and capecitabine as first-line chemotherapy (44.2 vs. 16.5 %) were more frequent in our cohort relative to the historical comparison. The median starting dose in our cohort was 633.5 mg/m(2). The CBR was similar between the CAPE-L and the standard dose cohorts (55.8 vs. 49.5 %), as was ORR (24.3 vs. 24 %), and median TTP (7 mo, 95 % CI 5.5-8.5 vs. 5.1 mo, 95 % CI 4.5-5.7). Median OS was longer in our cohort (24 mo, 95 % CI 16.8-31.2) than the historic standard dose cohort (12.1 mo, 95 % CI 9.6-14.4), a difference that was likely explained by the higher proportion of patients in the CAPE-L cohort who received capecitabine as first-line chemotherapy and who had hormone receptor positive disease. As expected, adverse events were less frequent with CAPE-L. We found that CAPE-L, which translates into a dose of 600-650 mg/m(2), appeared to have good clinical efficacy and acceptable toxicity.

Background There has been a growing interest in the development and application of alternative decision-making frameworks within health care, including multicriteria decision analysis (MCDA). Even though the literature includes several reviews on MCDA methods, applications of MCDA in oncology are lacking. Aim The aim of this paper is to discuss a rationale for the use of MCDA in oncology. In this context, the following research question emerged: How can MCDA be used to develop a clinical decision support tool in oncology? Methods In this paper, a brief background on decision making is presented, followed by an overview of MCDA methods and process. The paper discusses some applications of MCDA, proposes research opportunities in the context of oncology and presents an illustrative example of how MCDA can be applied to oncology. Findings Decisions in oncology involve trade-offs between possible benefits and harms. MCDA can help analyse trade-off preferences. A wide range of MCDA methods exist. Each method has its strengths and weaknesses. Choosing the appropriate method varies depending on the source and nature of information used to inform decision making. The literature review identified eight studies. The analytical hierarchy process (AHP) was the most often used method in the identified studies. Conclusion Overall, MCDA appears to be a promising tool that can be used to assist clinical decision making in oncology. Nonetheless, field testing is desirable before MCDA becomes an established decision-making tool in this field.

ASGE and ESGE guidelines recommend endoscopic metal stent placement for pancreatic carcinoma patients with biliary obstruction, and whose estimated life expectancy is greater than 6 months. Because median overall survival (OS) of metastatic pancreatic adenocarcinoma until recently has been less than 6 months, plastic biliary stents were preferentially placed rather than metal due to the greater upfront cost of the latter. Recent advances in the treatment of metastatic pancreatic cancer have extended median OS beyond the 6-month range. Given this improvement in OS, we performed a cost-effectiveness analysis of initial metal biliary versus plastic stent placement in metastatic pancreatic cancer patients with biliary obstruction. A Markov model was developed to predict lifetime costs, quality-adjusted life years (QALYs), and cost effectiveness of metal compared with plastic stents. Adult patients entered the model with locally advanced cancer and underwent endoscopic retrograde cholangiopancreatography (ERCP) with placement of metal or plastic stents. A targeted literature search was conducted to identify published sources, which were used to estimate clinical, cost, utility, and event rate inputs to the model. Results were estimated from the third-party payer perspective in 2012 US dollars per QALY. One-way and probabilistic sensitivity analyses were conducted to assess the impact on model outcomes resulting from uncertainty among inputs. Our analysis found that initial placement of metal stents was more cost effective than plastic biliary stents with lower overall costs due to lower restenting rates while at the same time associated with a better quality of life. Based on model projections, placement of metal stents could save approximately $1450 per patient over a lifetime, while simultaneously improving quality of life. These findings were robust in sensitivity analyses. Placement of metal biliary stents at initial onset of obstructive jaundice in adult patients with metastatic pancreatic carcinoma with an expected OS greater than 6 months was found to be a more cost-effective strategy than plastic stents. These results reinforce guidelines’ suggestions for metal stent placement.

The selection of the most appropriate treatment combinations requires the balancing of benefits and harms of these treatment options as well as the patients' preferences for the resulting outcomes.This research aimed at estimating and comparing the utility weights between elderly women with early stage hormone receptor positive (HR+) breast cancer receiving a combination of radiotherapy and hormonal therapy after breast conserving surgery (BCS) and those receiving a combination of BCS and hormonal therapy.The Surveillance, Epidemiology, and End Results (SEER) linked with Medicare Health Outcomes Survey (MHOS) was used as the data source. Health utility weights were derived from the VR-12 health-related quality of life instrument using a mapping algorithm. Descriptive statistics of the sample were provided. Two sample t-tests were performed to determine potential differences in mean health utility weights between the two groups after propensity score matching.The average age at diagnosis was 72 vs. 76 years for the treated and the untreated groups, respectively. The results showed an inverse relationship between the receipt of radiotherapy and age. Patients who received radiotherapy had, on average, a higher health utility weight (0.70; SD = 0.123) compared with those who did not receive radiotherapy (0.676; SD = 0.130). Only treated patients who had more than two comorbid conditions had significantly higher health utility weights compared with patients who were not treated.The mean health utility weights estimated for the radiotherapy and no radiotherapy groups can be used to inform a comparative cost-effectiveness analysis of the treatment options. However, the results of this study may not be generalizable to those who are outside a managed care plan because MHOS data is collected on managed care beneficiaries.

64 Background: In the era of increasing therapeutic options and complexity of disease, some cancer patients (pts) continue aggressive treatment even within days of death. Previous studies report 30-66% of pts do not receive hospice or palliative services in the last month of life and many are enrolled in hospice < 3 days before death. Quality measures are endorsed by ASCO, National Quality Forum, and Oncology Care Model to increase hospice utilization. It is shown that pts enrolled in hospice have increased survival time with reduced in-hospital resources. These benefits increase the longer pts are in hospice. We hypothesize early identification of high risk pts by a multidisciplinary group and formulation of a care plan will prompt early discussion for hospice eligibility, increasing referrals to hospice and the number of days spent in hospice. Methods: As reported (ASCO 2018, Abst 6547), an Interdisciplinary Care Team (ICT) was created with palliative medicine and oncology physicians, nurses, and social workers. Twice monthly pts with high utilization over a 60-day period were identified. Care plans (CP) were created using a team based approach with parallel input from outpatient teams. CP was communicated back to the primary team. Results: 112 pts were discussed over 24 months; 39 pts died with a solid tumor malignancy and this was our study cohort. 85% pts (33/39) were referred to or had a hospice discussion and 82% pts (27/33) enrolled. 6 pts declined and 6 acutely died. Of the 27 pts that entered hospice 78% (21/27) were enrolled > 3 days and 22 % (6/27) < 3 days. Average number days in hospice was 19.7 (median 11) for all who entered hospice. In the subgroup that were enrolled for > 3 days, average number days was 25 (median 21). 62% pts (17/27) entered hospice within 60 days of ICT meeting and CP. Conclusions: Early identification of high-utilizing cancer patients along with review by ICT may correlate with early recognition of hospice eligibility, enrollment, and therefore greater number days spent in hospice. This increases hospice utilization allowing patients and families to experience the full benefit of hospice-directed care. Further interventions should be explored in optimizing transitions of care.

e18184 Background: Venous thromboembolism (VTE) complicates several anti-cancer regimens including chemotherapy and anti-angiogenic agents. Cyclin-dependent kinase 4/6 inhibitors (CDKIs) are a new approach for hormone receptor positive (HR+) metastatic breast cancer (mBC). Reported VTE rates in randomized trials range from 0.6% for ribociclib (MONALEESA-2) to 2% for palbociclib (PALOMA-3) and 5% for abemaciclib (MONARCH-3) but these may underestimate actual rates compared to patients in clinical practice who are generally older and have greater comorbidities. Little is known about real world incidence or prevalence of VTE with CDKIs in mBC. The aim of this study was to evaluate rates of VTE in clinical practice and association with outcomes in mBC patients on CDKIs. Methods: We conducted a retrospective cohort study at Cleveland Clinic Taussig Cancer Institute, approved by the institutional review board. We identified consecutive mBC patients who received any of three FDA-approved CDKIs (palbociclib, ribociclib, abemaciclib) from 1/2015 through 12/2017. VTE including deep venous thrombosis (DVT) and pulmonary embolism (PE) were identified by electronic medical record review. Overall survival (OS), progression free survival (PFS) and time to VTE were estimated by the Kaplan-Meier method and evaluated for association with VTE using Cox proportional hazard regression. Results: The study population included 424 patients, with a median age at diagnosis of 54.76 yrs, (range 27 -85). Palbociclib was the most commonly used CDKI (n = 390, 91.8%); 27 patients (6.3%) received more than one drug. VTE during CDKI therapy occurred in 9% of patients (n = 38), including DVT in 52.6% (n = 20), PE in 18.5% (n = 7) and visceral vein thrombosis (VVT) in 15.8% (n = 6). Median time to VTE was 314 days, and 6-months rate was 4.1%. VTE was associated with numerically worse PFS and OS, but this was not statistically significant (PFS [HR 1.25, 95% CI 0.73 – 2.14, p = 0.42], OS [HR 1.60, 95% CI 0.89 – 2.87, p = 0.12]). Conclusions: VTE affected nearly 10% of breast cancer patients receiving CDKIs, 2- to 5-fold greater than reported in registration trials. Further work is necessary to identify pathophysiology, risk factors and benefit of thromboprophylaxis.

e12515 Background: Women with stage IV HER2+ breast cancer typically have longer overall survival (OS) compared to other breast cancer subsets due to the effectiveness of dual anti HER-2 antibody therapy. The role of mastectomy remains controversial. Methods: We reviewed patients who were diagnosed with stage IV HER2+ breast cancer between 2/2015 and 12/2017 at Cleveland Clinic. Overall survival (OS) was estimated by the Kaplan-Meier method, and compared by the log-rank test. Univariable and multivariable analysis were performed using Cox regression to identify predictors of OS. Results: We identified 47 patients, with a median age of 58 (range: 22 – 87). Twenty-eight (60%) and 14 (30%) patients had ER+ and PR+ disease, respectively. Four patients had brain metastasis at time of stage IV diagnosis. All patients received systemic therapy. 17 (36%) patients underwent mastectomy after diagnosis of stage IV breast cancer,. Of the 30 (64%) patients who did not undergo mastectomy, 24 (80%), 2 (7%), and 4 (13%) were treated with both chemotherapy and HER2-directed therapy, chemotherapy alone, and HER2-directed therapy alone, respectively. Breast radiotherapy was performed on 9 (53%) and 8 (27%) patients in mastectomy and no mastectomy cohorts, respectively. Median follow-up time was 22 months . The two-year OS for mastectomy and no mastectomy cohorts were 94% (95% CI: 83 – 100) and 50% (95% CI: 33 – 76), respectively (p=0.009). On univariable analysis, only mastectomy vs no mastectomy (HR: 0.18, 95% CI: 0.04 – 0.80, p=0.025) predicted OS. On multivariable analysis, mastectomy vs no mastectomy has remained to be statistically significant predictor of OS (HR: 0.08, 95% CI: 0.01 – 0.66, p=0.019), whereas age, chemotherapy, HER2-directed therapy, and breast radiation were not independent predictors of improved OS (p>0.05). Conclusions: In our cohort, mastectomy was an independent predictor of longer OS in women with stage IV HER2+ breast cancer.

e12538 Background: CDK inhibitors (CDKi), in combination with aromatase inhibitors (AI), are approved for the treatment of hormone receptor positive (HR+) Her2 negative metastatic breast cancer (MBC). The effectiveness of continuing CDKi beyond first disease progression is not known. This study evaluated real world evidence and assessed the impact of continuation of CDKi beyond first disease progression in combination with endocrine therapy. Methods: This is a retrospective, single institution review of HR+ MBC patients treated with CDKi from 2015-2018 who continued CDKi after initial progression. The primary outcome was progression-free survival (PFS) beyond first disease progression, as assessed by the clinician based on radiological and/or clinical criteria. Overall survival (OS) – defined as date of initial CDKi treatment to date of death or last follow up – was a secondary outcome. Results: 30 women with HR+/HER2- MBC, median age 47.5 years (range: 31 – 81), sequentially continued on CDKi beyond first progression were identified from a database of patients treated with Palbociclib. Median and average follow up times on CDKi were 27.18 and 24.53 months, respectively. Initial endocrine/CDKi regimen received included: palbociclib (PA)/letrozole (LTZ) [67%], PA/fulvestrant (FULV) [23%], and PA/other AI [10%]. Prescribed combinations beyond 1st progression were: PA/FULV [56.7%], PA/LTZ [16.7%], and PA/other AI [20%], abemaciclib plus LTZ or FULV [6%]. As of 1/31/2019, 25 patients (83.3%) were still alive, and 19 (63%) had undergone a second progression on CDKi. The estimated median PFS for the entire duration while on CDKi was 23.5 months (95% CI 12.8 – 27.8), of which 11.8 months (95% CI 5.34 – 13.13) was the median PFS beyond first progression. The estimated median OS was 45.4 months. Conclusions: Among a small cohort of HR+ MBC patients, in a non-clinical trial setting, continuation of palbociclib plus endocrine therapy beyond first progression was associated with a median PFS of approximately 11 months. Formal clinical evaluation of continuation of CDK inhibitor plus endocrine therapy beyond first progression is warranted.

Background Statins are established as first line therapy in patients with hypercholesterolemia and are thought to have pleiotropic effects including inhibition of signaling pathways known to drive cell proliferation and survival responses. Numerous preclinical and observational studies have demonstrated activity and improved outcomes in breast cancer patients who received statins, particularly lipophilic statins, as part of their adjuvant therapy. In the Life After Cancer Epidemiology (LACE) Study, 1,945 early-stage breast cancer survivors were shown to have a 33% decreased risk of breast cancer recurrence with post-diagnosis statin use, an effect that was magnified with increasing duration of statin use. We hypothesized that statin use concurrent with trastuzumab based chemotherapy in patients treated for non-metastatic HER2 positive breast cancer would be associated with improved outcomes. Methods We performed a retrospective review of all patients (n = 300) with HER2+ breast cancer who received trastuzumab from 2006-2012 at UM/SCCC. We identified two groups of patients for comparison - those who received statins (ST) during adjuvant chemotherapy (n = 45) or no statins during chemotherapy (NST) during adjuvant chemotherapy (n = 200). Patients with unclear documentation of concurrent statin use, men, patients with de-novo-metastatic breast cancer or prior primary cancer, bilateral breast cancers, and patients without follow-up were excluded. 5-year disease free (DFS) and overall survival (OS) were calculated. A univariate analysis was performed. Multivariate analysis for time-to-event data, using the Cox and extended Cox regression model will be performed and reported. Results The median age at diagnosis was 58 and 48, in the ST and NST groups, respectively. The most commonly used statin was lipophilic simvastatin (34.1%). The average baseline and post chemotherapy total cholesterol level in the ST group was 200.8 and 218.1mg/dL, respectively. Descriptive characteristics of the ST and NST groups respectively are as follows: postmenopausal (77.8% vs. 43.5%) tumor size 30 (40.0% vs. 27.0%), and concomitant metformin (28.9% vs. 11.5%). The NST group was more likely to have a reduction of greater than 10% in their EF (9.0% vs. 6.7%). At a median follow-up of 32 and 26 months, the estimated 5-year DFS was significantly improved in the ST group (81.8% vs. 51.5%, p = 0.046). Meanwhile, the estimated 5-year OS was not significantly different between both groups (93.4% vs. 91.6%, p = 0.121). Metformin was not associated with a significant improvement in DFS or OS. Conclusion Our study demonstrated that statin use concurrent with trastuzumab-based chemotherapy for non-metastatic HER2 breast cancer was associated with improved estimated 5-year DFS, but not OS. The retrospective nature of our study does not allow for a definitive answer but further research needs to be done to define the role of statins in HER2+ breast cancer treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-09-03.

Background: The 21 gene RT-PCR assay (Oncotype Dx, Genomic Health, Inc, Redwood City, CA) performed on formalin-fixed paraffin-embedded tissue quantifies the likelihood of distant recurrence in patients with estrogen receptor (ER)-positive, axillary lymph node-negative breast cancer. The 21 gene recurrence score (RS) also quantifies the magnitude of clinical benefit of adjuvant cytotoxic chemotherapy to endocrine therapy. Patients with a high risk RS clearly benefit from the addition of adjuvant chemotherapy, while patients with a low RS do not. However, approximately one-third of patients have an intermediate RS (18-31) and the incremental benefit from adjuvant chemotherapy is unclear. The primary objective of this study was to evaluate the clinical outcomes of early stage breast cancer patients with intermediate RS. Methods: We identified 262 patients with intermediate RS (18-31) in a prospectively maintained registry of patients with Oncotype Dx testing at the Cleveland Clinic from 2004-2013. ER status, progesterone receptor (PR) status, HER2 gene amplification, treatment with chemotherapy, follow-up for distant recurrences and other clinical and pathological variables were collected for all patients in the registry. Results: Patient characteristics are listed in Table 1. One hundred patients (38.2 %) were treated with chemotherapy plus endocrine therapy, while 156 (59.5%) were treated with endocrine therapy alone. Treatment data was unavailable for 6 patients (2%). Distant recurrence status is unknown for 2 patients. The overall rate of distant plus local recurrence for all 262 patients was 3.8% (3 local and 7 distant recurrences). There were 6 and 4 recurrences respectively, for patients received chemotherapy plus endocrine therapy (6%), and in patients treated with endocrine therapy alone (2.5%), which was not significantly different (p=.21). Table 1. Patient CharacteristicsMedian age at diagnosis (Range)58 (27-88)Median RS (Range)22 (18-31)ER+ (%)262 (99.6)PR+ (%)234 (89)HER-2 amplified (%)10 (3.8)Grade (%) 184 (32.8)2136 (53.1)336 (14.1)Histology (%) Ductal187 (71.1%)Lobular45 (17.1%)Mixed31 (11.8%)Median Tumor size (range)1.6 cm (0.2-6.5)Lymph Node Status (%) pN0238 (90.8)1-3 positive nodes24 (9.2) Conclusions: With a median follow-up of 45 months, our data indicate that the realized distant recurrence rate for patients with an intermediate range RS was less than 5%. These data do not exclude the possibility that some patients with an intermediate RS may derive a small incremental benefit from the addition of adjuvant chemotherapy. Larger, randomized prospective trials like TAILORx should provide additional guidance for the management of this patient population. Citation Format: Lindsey M Goodman, Alberto J Montero, Lisa Rybicki, Karen Mrazeck, Benjamin Calhoun, Raymond Tubbs, Halle Moore. Clinical outcomes of breast cancer patients with intermediate oncotype DX recurrence scores (RS): A review of the Cleveland Clinic Experience [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-46.

nab-Paclitaxel has been shown to disrupt pancreatic cancer stroma and was effective in combination with gemcitabine in a phase I/II trial. This study was designed to determine the efficacy of nab-paclitaxel monotherapy in previously treated pancreatic cancer patients.In this phase II trial, patients with advanced pancreatic cancer who progressed on gemcitabine-based therapy, received nab-paclitaxel 100 mg/m over 30 minutes on days 1, 8, and 15 of a 28-day cycle. The primary endpoint was 6-month overall survival (OS). Secondary endpoints were response rate (by Response Evaluation Criteria In Solid Tumors), progression-free survival, safety, and toxicity profile.Among 19 patients treated, the median age was 61 years, 9 (47%) were male patients and 18 (95%) had stage-IV disease. The primary endpoint of the study was reached with a 6-month OS of 58% [95% confidence interval (95% CI), 33%-76%] and an estimated median OS of 7.3 months (95% CI, 2.8-15.8 mo). The median progression-free survival was 1.7 months (95% CI, 1.5-3.5 mo). One patient had a confirmed partial response and 6 (32%) had stable disease as their best response. Nonhematological toxicities were generally mild with grades 1-2 nausea, anorexia, hypocalcemia, and vomiting occurring in 63%, 47%, 37%, and 26% of patients, respectively. Grades 3-4 neutropenia, neutropenic fever, and anemia occurred in 32%, 11%, and 11% of patients, respectively. Only 2 of 15 available tumors stained positive for secreted protein acid rich in cysteine, and neither of these patients benefited from the therapy.nab-Paclitaxel was well tolerated, and it demonstrated preliminary evidence of activity in a subset of patients who progressed on gemcitabine-based therapy.

There is no consensus on the most effective modality for the treatment of resectable esophageal adenocarcinomas (EAC). We theorized that treatment modality may influence survival differently depending on the stage of disease. A single-institution, retrospective examination of resectable EAC between 2000 and 2008 was performed. Resectable EAC were stratified into early disease (stage 2a or less) and late disease (stage 2b or more) based on pretreatment endoscopic ultrasound (EUS). Patients with T4, >N2, and/or distant disease were excluded. A total of 156 patients were included in this study. Most patients were white (97 %), male (83 %), and over 60 years of age (51 %). Patients with early disease on pretreatment EUS exhibited improved overall survival compared to patients with late disease (P

For many years, the medical treatment of breast cancer was reliant solely on cytotoxic chemotherapy. However, over the past twenty years, treatment has evolved to a more target-directed approach. We now employ tailored therapy based on the presence or absence of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER2). We expect this trend to continue, as agents that use novel approaches to target HER2, as well as targeting different portions of the HER signaling pathway, are in various stages of development. Notably, pertuzumab, a humanized monoclonal antibody that binds to a different domain of the extracellular portion of the HER2 receptor than trastuzumab, was recently approved for use, as was lapatinib, a small-molecule tyrosine kinase inhibitor. Patients with triple negative breast cancer, particularly those with the BRCA mutation, have more limited treatment options and carry a worse prognosis than those who are hormone receptor positive. However, recent data has shown that PARP inhibitors may have significant anti-tumor effect in those with this subtype of breast cancer. Novel agents that inhibit mTOR, PI3K, the insulin-like growth factor, heat shock protein 90, and histone deacetylase have shown promise in phase I-III trials and offer exciting new possibilities for the treatment of this often fatal disease. As we are presented with an ever increasing number of treatment options, the timing and combinations of therapeutic agents used becomes ever more complex in the age of personalized care, but we are hopeful that ultimately this will lead to improved patient outcomes.