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Purpose Notch signaling dysregulation is implicated in the development of pancreatic adenocarcinoma (PDAC). Tarextumab is a fully human IgG2 antibody that inhibits Notch2/3 receptors. Patients and methods Aphase 2, randomized, placebo-controlled, multicenter trial evaluated the activity of tarextumab in combination with nab-paclitaxel and gemcitabine in patients with metastatic PDAC. Patients were stratified based on ECOG performance score and Ca 19-9 level and randomized 1:1 to nab-paclitaxel, gemcitabine with either tarextumab or placebo. Based on preclinical and phase Ib results suggesting a positive correlation between Notch3 gene expression and tarextumab anti-tumor activity, patients were also divided into subgroups of low, intermediate, and high Notch3 gene expression. Primary endpoint was overall survival (OS) in all and in patients with the three Notch3 gene expression subgroups (≥25th, ≥50% and ≥75% percentiles); secondary end points included progression-free survival (PFS), 12-month OS, overall response rate (ORR), and safety and biomarker investigation. Results Median OS was 6.4 months in the tarextumab group vs 7.9 months in the placebo group (HR = 1.34 [95% CI = 0.95, 1.89], P = .0985). No difference observed in OS in the Notch3 gene expression subgroups. PFS in the tarextumab-treated group (3.7 months) was significantly shorter compared with the placebo group (5.5 months) (hazard ratio was 1.43 [95% CI = 1.01, 2.01]; P = .04). Grade 3 diarrhea and thrombocytopenia were more common in the tarextumab group. Conclusions The addition of tarextumab to nab-paclitaxel and gemcitabine did not improve OS, PFS, or ORR in first-line metastatic PDAC, and PFS was specifically statistically worse in the tarextumab-treated patients. Clinical trial registry no NCT01647828.

Background Fear of recurrence (FoR) is a prevalent concern among breast cancer survivors (BCS), yet few accessible interventions exist. This study evaluated a targeted eHealth intervention, “FoRtitude,” to reduce FoR using cognitive behavioral skills training and telecoaching. Methods BCS (N = 196) were recruited from an academic medical center and 3 National Cancer Institute Community Oncology Research Program community sites, had stage 0-III breast cancer, were 1-10 years postprimary treatment, with moderate to high FoR and familiarity with the internet. Using the Multiphase Optimization Strategy, participants were independently randomly assigned to 3 cognitive behavioral skills (relaxation, cognitive restructuring, worry practice) vs an attention control condition (health management content [HMC]) and to telecoaching (motivational interviewing) vs no telecoaching. Website content was released across 4 weeks and included didactic lessons, interactive tools, and a text-messaging feature. BCS completed the Fear of Cancer Recurrence Inventory at baseline and at 4 and 8 weeks. Fear of Cancer Recurrence Inventory scores over time were compared using mixed-effects models. All statistical tests were 2-sided. Results FCRI scores [SD] decreased statistically significantly from baseline to postintervention (T0 = 53.1 [17.4], T2 = 41.9 [16.2], P Conclusions BCS experienced statistically significant reductions in FoR postintervention, but improvements were comparable between CBT and attention controls. Telecoaching improved adherence and retention. Future research is needed on optimal integration of CBT and HMC, dose, and features of eHealth delivery that contributed to reducing FoR. In the COVID-19 era, remote delivery has become even more essential for reaching survivors struggling with FoR.

Introduction Multimodality therapy has curative potential in locally advanced NSCLC. Mediastinal nodal sterilization (MNS) after induction chemoradiotherapy (CRT) can serve as an intermediate marker for efficacy. NRG Oncology Radiation Therapy Oncology Group (RTOG) 0229 demonstrated the feasibility and efficacy of combining full-dose radiation (61.2 Gy) with chemotherapy followed by resection and chemotherapy. On the basis of that experience and evidence that EGFR antibodies are radiosensitizing, we explored adding panitumumab to CRT followed by resection and consolidation chemotherapy in locally advanced NSCLC with a primary end point of MNS. Methods Patients with resectable locally advanced NSCLC were eligible if deemed suitable for trimodality therapy before treatment. Surgeons were required to demonstrate expertise after CRT and adhere to specific management guidelines. Concurrent CRT consisted of weekly carboplatin (area under the curve = 2.0), paclitaxel (50 mg/m2), and 60 Gy of radiation therapy delivered in 30 fractions. There was a 2:1 randomization in favor of panitumumab at 2.5 mg/kg weekly for 6 weeks. The mediastinum was pathologically reassessed before or at the time of resection. Consolidation chemotherapy was weekly carboplatin (area under the curve = 6) and paclitaxel, 200 mg/m2 every 21 days for two courses. The study was designed to detect an improvement in MNS from 52% to 72%. With use of a 0.15 one-sided type 1 error and 80% power, 97 patients were needed. Results The study was opened in November 2010 and closed in August 2015 by the Data Monitoring Committee after 71 patients had been accrued for futility and excessive toxicity in the experimental arm. A total of 60 patients were eligible: 19 patients (86%) who received CRT and 29 (76%) who received CRT plus panitumumab and underwent an operation. With regard to postoperative toxicity, there were three grade 4 adverse events (13.6%) and no grade 5 adverse events (0%) among those who received CRT versus six grade 4 (15.8%) and four grade 5 adverse events (10.5%) among those who received CRT plus panitumumab. The MNS rates were 68.2% (95% confidence interval: 45.1–86.1) and 50.0% (95% confidence interval: 33.4–66.6) for CRT and CRT plus panitumumab, respectively (p = 0.95). Conclusion The addition of panitumumab to CRT did not improve MNS. There was an unexpectedly high mortality rate in the panitumumab arm, although the relationship to panitumumab is unclear. The control arm had outcomes similar to those in NRG Oncology RTOG 0229.

Background With increased understanding of the unique entities, subtype-specific approaches for peripheral T-cell lymphoma (PTCL) are emerging, and more precise diagnoses are becoming increasingly important. Patients and Methods We analyzed the approach to the histopathologic diagnosis of PTCL using data from the comprehensive oncology measures of peripheral T-cell lymphoma (COMPLETE) study. The COMPLETE trial is a large prospective cohort study of patients with newly diagnosed PTCL in the United States. Results A total of 499 patients were enrolled from 40 academic and 15 community-based centers. Baseline assessment forms were collected for 493 patients, of which 435 (88%) were available for analysis. The most common diagnoses were PTCL, not otherwise specified (PTCL-NOS), anaplastic large cell lymphoma, and angioimmunoblastic T-cell lymphoma (AITL). A mean of 10 markers (range, 0-21) was assessed per patient. CD30 was assessed frequently but not uniformly in cases that were not anaplastic large cell lymphoma. Only 17% of PTCL-NOS cases were assessed for PD1. CXCL13 was a relatively sensitive marker in AITL, expressed in 84% of tested cases; however, only 3% of PTCL-NOS cases were tested. T follicular helper cell marker assessment differed between academic and community practices, with PD1 more often evaluated by academic centers in cases of AITL (62% vs. 12%; P = .01). Conclusion The diagnostic workup for PTCL in the United States varies widely and often lacks important phenotypic information to fully characterize the lymphoma. Gaps in testing of selected markers should be filled, given the impending revision to the World Health Organization classification. The accuracy of diagnosis will become increasingly important as we enter the era of targeted treatment for PTCL.

Background: Outcomes for patients with peripheral T-cell lymphoma (PTCL) who fail to achieve complete response (CR) or relapse after front-line therapy are poor with lack of prospective outcomes data. Objectives: COMPLETE is a prospective registry of 499 patients enrolled at academic and community sites in the United States detailing patient demographics, treatment and outcomes for patients with aggressive T cell lymphomas. We report results for patients with primary refractory and relapsed disease. Methods: Primary refractory disease was defined as an evaluable best response to initial treatment (induction ± maintenance or consolidation/transplant) other than CR, and included a partial response, progressive disease, or no response/stable disease. Relapsed disease was defined as an evaluable best response to initial treatment of CR, followed by disease progression at a later date, irrespective of time to progression. Patients were included in the analysis if initial treatment began within 30 days of enrollment and treatment duration was ≥4 days. Results: Of 420 evaluable patients, 97 met the definition for primary refractory and 58 with relapsed disease. In the second-line setting, relapsed patients received single-agent therapies more often than refractory patients (52 vs. 28%; p = 0.01) and were more likely to receive single-agent regimens (74 vs. 53%; p = 0.03). The objective response rate to second-line therapy was higher in relapsed patients (61 vs. 40%; p = 0.04) as was the proportion achieving a CR (41 vs. 14%; p = 0.002). Further, relapsed patients had longer overall survival (OS) compared to refractory patients, with a median OS of 29.1 versus 12.3 months. Conclusions: Despite the availability of newer active single agents, refractory patients were less likely to receive these therapies and continue to have inferior outcomes compared to those with relapsed disease. PTCL in the real world remains an unmet medical need, and improvements in front-line therapies are needed.

BACKGROUND Long-term survival in patients with aggressive peripheral T-cell lymphoma (PTCL) is generally poor, and there currently is no clear consensus regarding the initial therapy used for these diseases. Herein, the authors analyzed treatment patterns and outcomes in a prospectively collected cohort of patients with a new diagnosis of nodal PTCL in the United States. METHODS Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment (COMPLETE) is a prospective multicenter cohort study designed to identify the most common prevailing treatment patterns used for patients newly diagnosed with PTCL in the United States. Patients with nodal PTCL and completed records regarding baseline characteristics and initial therapy were included in this analysis. All statistical tests were 2-sided. RESULTS Of a total of 499 patients enrolled, 256 (51.3%) had nodal PTCL and completed treatment records. As initial therapy, patients received doxorubicin-containing regimens (41.8%), regimens containing doxorubicin plus etoposide (20.9%), other etoposide regimens (15.8%), other single-agent or combination regimens (19.2%), and gemcitabine-containing regimens (2.1%). Survival was found to be statistically significantly longer for patients who received doxorubicin (log-rank P = .03). After controlling for disease histology and International Prognostic Index, results demonstrated a trend toward significance in mortality reduction in patients who received doxorubicin compared with those who did not (hazard ratio, 0.71; 95% confidence interval, 0.48-1.05 [P = .09]). CONCLUSIONS To the authors' knowledge, there is no clear standard of care in the treatment of patients with PTCL in the United States. Although efforts to improve frontline treatments are necessary, anthracyclines remain an important component of initial therapy for curative intent. Cancer 2017;123:1174–1183. © 2016 American Cancer Society.

Background The role of autologous stem cell transplantation (ASCT) in the first complete remission (CR1) of peripheral T-cell lymphomas (PTCLs) is not well defined. This study analyzed the impact of ASCT on the clinical outcomes of patients with newly diagnosed PTCL in CR1. Methods Patients with newly diagnosed, histologically confirmed, aggressive PTCL were prospectively enrolled into the Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE) study, and those in CR1 were included in this analysis. Results Two hundred thirteen patients with PTCL achieved CR1, and 119 patients with nodal PTCL, defined as anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), or PTCL not otherwise specified, were identified. Eighty-three patients did not undergo ASCT, whereas 36 underwent consolidative ASCT in CR1. At the median follow-up of 2.8 years, the median overall survival was not reached for the entire cohort of patients who underwent ASCT, whereas it was 57.6 months for those not receiving ASCT (P = .06). ASCT was associated with superior survival for patients with advanced-stage disease or intermediate-to-high International Prognostic Index scores. ASCT significantly improved overall and progression-free survival for patients with AITL but not for patients with other PTCL subtypes. In a multivariable analysis, ASCT was independently associated with improved survival (hazard ratio, 0.37; 95% confidence interval, 0.15-0.89). Conclusions This is the first large prospective cohort study directly comparing the survival outcomes of patients with nodal PTCL in CR1 with or without consolidative ASCT. ASCT may provide a benefit in specific clinical scenarios, but the broader applicability of this strategy should be determined in prospective, randomized trials. These results provide a platform for designing future studies of previously untreated PTCL.

Purpose Veliparib, a poly (ADP ribose) polymerase inhibitor, potentiated standard chemotherapy against small-cell lung cancer (SCLC) in preclinical studies. We evaluated the combination of veliparib with cisplatin and etoposide (CE; CE+V) doublet in untreated, extensive-stage SCLC (ES-SCLC). Materials and Methods Patients with ES-SCLC, stratified by sex and serum lactate dehydrogenase levels, were randomly assigned to receive four 3-week cycles of CE (75 mg/m2 intravenously on day 1 and 100 mg/m2 on days 1 through 3) along with veliparib (100 mg orally twice per day on days 1 through 7) or placebo (CE+P). The primary end point was progression-free survival (PFS). Using an overall one-sided 0.10-level log-rank test, the study had 88% power to demonstrate a 37.5% reduction in the PFS hazard rate. Results A total of 128 eligible patients received treatment on protocol. The median age was 66 years, 52% of patients were men, and Eastern Cooperative Oncology Group performance status was 0 for 29% of patients and 1 for 71%. The respective median PFS for the CE+V arm versus the CE+P arm was 6.1 versus 5.5 months (unstratified hazard ratio [HR], 0.75 [one-sided P = .06]; stratified HR, 0.63 [one-sided P = .01]), favoring CE+V. The median overall survival was 10.3 versus 8.9 months (stratified HR, 0.83; 80% CI, 0.64 to 1.07; one-sided P = .17) for the CE+V and CE+P arms, respectively. The overall response rate was 71.9% versus 65.6% (two-sided P = .57) for CE+V and CE+P, respectively. There was a significant treatment-by-strata interaction in PFS: Male patients with high lactate dehydrogenase levels derived significant benefit (PFS HR, 0.34; 80% CI, 0.22 to 0.51) but there was no evidence of benefit among patients in other strata (PFS HR, 0.81; 80% CI, 0.60 to 1.09). The following grade ≥ 3 hematology toxicities were more frequent in the CE+V arm than the CE+P arm: CD4 lymphopenia (8% v 0%; P = .06) and neutropenia (49% v 32%; P = .08), but treatment delivery was comparable. Conclusion The addition of veliparib to frontline chemotherapy showed signal of efficacy in patients with ES-SCLC and the study met its prespecified end point.

Background and Objectives Study objectives, included determination of: (i) associations between radiologic and pathologic responses of colorectal cancer liver metastases (CRCLM) to chemotherapy; and (ii) whether CRCLM histopathology is associated with recurrence free survival (RFS) after resection among patients not treated with pre-operative chemotherapy (untreated). Methods Demographics, clinicopathologic characteristics, and outcomes among patients who underwent CRCLM resection from 2007 to 2014 were reviewed. Tumor regression grade (TRG) of 1–2 and 4–5 depict low and high proportions of viable tumor relative to fibrosis, respectively. Results Of 138 patients, 84 (60.9%) were treated with pre-operative chemotherapy. In these patients, there was no difference in proportions with TRG 1–2 among those with verses without radiologic response (26.9% vs. 18.8%, P = 0.393). TRG 1–2 was associated with superior RFS on univariable (median 15 vs. 6 months, P

Purpose The purpose of this study was to compare illness-related anxiety among participants in the Rituximab Extended Schedule or Retreatment Trial (RESORT) randomly assigned to maintenance rituximab (MR) versus rituximab re-treatment (RR). A secondary objective was to examine whether the superiority of MR versus RR on anxiety depended on illness-related coping style. Patients and Methods Patients (N = 253) completed patient-reported outcome (PRO) measures at random assignment to MR or RR (baseline); at 3, 6, 12, 24, 36, and 48 months after random assignment; and at rituximab failure. PRO measures assessed illness-related anxiety and coping style, and secondary end points including general anxiety, worry and interference with emotional well-being, depression, and health-related quality of life (HRQoL). Patients were classified as using an active or avoidant illness-related coping style. Independent sample t tests and linear mixed-effects models were used to identify treatment arm differences on PRO end points and differences based on coping style. Results Illness-related anxiety was comparable between treatment arms at all time points (P > .05), regardless of coping style (active or avoidant). Illness-related anxiety and general anxiety significantly decreased over time on both arms. HRQoL scores were relatively stable and did not change significantly from baseline for both arms. An avoidant coping style was associated with significantly higher anxiety (18% and 13% exceeded clinical cutoff points at baseline and 6 months, respectively) and poorer HRQoL compared with an active coping style (P < .001), regardless of treatment arm assignment. Conclusion Surveillance until RR at progression was not associated with increased anxiety compared with MR, regardless of coping style. Avoidant coping was associated with higher anxiety and poorer HRQoL.

Clinical management of microinvasive breast cancer (Tmic) remains controversial. Although metastases are infrequent in Tmic carcinoma patients, surgical treatment typically includes lymph node sampling. The objective of this study was to determine the rate and predictors of lymph node metastases, recurrence, and survival in a large series of Tmic breast carcinomas. Consecutive cases of Tmic were identified within our health care system from 2001 to 2015. We reviewed results of lymph node sampling and other pathologic factors including hormone receptor/HER2 status, associated in situ tumor size/grade, margin status, number of invasive foci, surgical/adjuvant therapies, and recurrence/survival outcomes. In this cohort, 294 Tmic cases were identified with mean follow-up of 4.6 years. Of 260 patients who underwent axillary staging, lymph node metastases were identified in 1.5% (all of which were ductal type). All Tmic cases with positive lymph node metastases had associated DCIS with size > 5 cm (5.3-8.5 cm) compared to a median DCIS tumor size of 2.5 cm (0.2-19.0 cm) for the entire cohort. No lymph node metastases were seen with microinvasive lobular carcinoma. During the follow-up period, there were no regional/distant recurrences or breast cancer-associated deaths in a mean follow-up period of 4.6 years. Two patients developed subsequent ipsilateral breast cancer (DCIS) in a different quadrant than the original Tmic. Clinical behavior of microinvasive breast cancer in this series is similar to DCIS. Lymph node metastases are uncommon and were only seen with ductal type microinvasive carcinoma. Our data suggest limited benefit for routine node sampling and support management of Tmic similar to DCIS, particularly for patients with DCIS

Objective To examine the tolerability and antitumor activity of trebananib plus pegylated liposomal doxorubicin (PLD) or topotecan in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. Methods In this open-label phase 1b study, patients received trebananib 10mg/kg or 15mg/kg IV QW plus PLD 50mg/m 2 (cohorts A1 and A3, respectively) or topotecan 4mg/m 2 (cohorts B1 and B3, respectively). Endpoints were dose-limiting toxicity (DLT; primary); treatment-emergent adverse events (AEs), overall response rate, anti-trebananib antibodies, and pharmacokinetics (secondary). Results 103 patients were enrolled. One patient in A1 and B1 had DLTs. Across all cohorts, the most common AEs were nausea, fatigue, and peripheral edema. Across both trebananib plus PLD cohorts (A1/A3), grade 4 AEs were pulmonary embolism, disease progression, and anemia. Two patients had grade 5 intestinal perforation (n=1) and sudden death (n=1). Across both trebananib plus topotecan cohorts (B1/B3), grade 4 AEs were neutropenia, hypokalemia, decreased granulocyte count, chest pain, dyspnea, decreased neutrophil count, and pulmonary embolism. Two patients had grade 5 disease progression. One patient had grade 5 pleural effusion associated with progressive disease. Confirmed objective response rates were 36.0% (A1), 34.8% (A3), 16.7% (B1), and 0.0% (B3). Median progression-free survival duration (months) was 7.4 (A1), 7.1 (A3), 3.5 (B1), and 3.1 (B3), respectively. No drug–drug interactions were apparent. Conclusions Trebananib 10mg/kg and 15mg/kg IV QW plus PLD or topotecan appear to have acceptable toxicity profiles in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. Antitumor activity was evident across all cohorts.

This clinical trial evaluated whether topotecan in combination with bevacizumab improved progression-free survival (PFS) in patients with advanced, refractory non--small-cell lung cancer in a second-line setting.Patients aged 18 years old and older received topotecan (4.0 mg/m(2)) on days 1, 8, and 15, and bevacizumab (10 mg/kg) on days 1 and 15 as intravenous infusions on a 28-day treatment cycle. Available tumor specimens were analyzed for ISG15 gene expression as a biomarker of response to topotecan.Forty-two patients were enrolled in the study, with a median age of 62.5 years and a median of 3 (range, 1-7) prior treatment regimens. Almost half (n = 18, 42.9%) of the patients received prior bevacizumab therapy. PFS was 5.1 months (95% CI, 3.7-7.8 months), and overall survival was 11.5 months (95% CI, 6.8-15.5 months). Response rates were as follows: 14.3% partial response, 54.8% stable disease, and 28.6% progressive disease. Hematologic toxicities included grade 3 thrombocytopenia (n = 7, 16.7%), neutropenia (n = 4, 9.5%), and anemia (n = 2, 4.8%). One toxic death occurred due to pulmonary hemorrhage, and one patient experienced a grade 4 pulmonary embolism. Grade 3 nonhematologic adverse events were uncommon (8%). There was a trend for improved median PFS, 3.5 months vs. 1.8 months (P = .26), in patients with high ISG15 expression.Bevacizumab in combination with topotecan as a salvage therapy for metastatic non--small-cell lung cancer is well tolerated and is worthy of further investigation.

BACKGROUND: ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings. METHODS: In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1-3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants. FINDINGS: Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1-5·3), patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0·73, 95% CI 0·57-0·92, p=0·0083). The 5-year invasive disease-free survival was 90·2% (95% CI 88·3-91·8) in the neratinib group and 87·7% (85·7-89·4) in the placebo group. Without diarrhoea prophylaxis, the most common grade 3-4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 [40%] grade 3 and one [BACKGROUND: ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings.METHODS: In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1-3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants.FINDINGS: Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1-5·3), patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0·73, 95% CI 0·57-0·92, p=0·0083). The 5-year invasive disease-free survival was 90·2% (95% CI 88·3-91·8) in the neratinib group and 87·7% (85·7-89·4) in the placebo group. Without diarrhoea prophylaxis, the most common grade 3-4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 [40%] grade 3 and one [INTERPRETATION: At the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses-ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast-without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events.FUNDING: Wyeth, Pfizer, and Puma Biotechnology.

To evaluate the frequency, risk factors, and clinical presentation of bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ).We performed a retrospective analysis of 576 patients with cancer treated with intravenous pamidronate and/or zoledronate between January, 2003 and December, 2007 at the University of Minnesota Masonic Cancer Center and Park Nicollet Institute.Eighteen of 576 identified patients (3.1%) developed BRONJ including 8 of 190 patients (4.2%) with breast cancer, 6 of 83 patients (7.2%) with multiple myeloma, 2 of 84 patients (2.4%) with prostate cancer, 1 of 76 patients (1.3%) with lung cancer, 1 of 52 patients (1.9%) with renal cell carcinoma, and in none of the 73 patients with other malignancies. Ten patients (59%) developed BRONJ after tooth extraction, whereas 7 (41%) developed it spontaneously (missing data for 1 patient). The mean number of BP infusions (38.1 ± 19.06 infusions vs. 10.5 ± 12.81 infusions; P0.001) and duration of BP treatment (44.3 ± 24.34 mo vs. 14.6 ± 18.09 mo; P0.001) were significantly higher in patients with BRONJ compared with patients without BRONJ. Multivariate Cox proportional hazards regression analysis showed that diabetes [hazard ratio (HR)=3.40; 95% confidence interval (CI), 1.14-10.11; P=0.028], hypothyroidism (HR=3.59; 95% CI, 1.31-9.83; P=0.013), smoking (HR=3.44; 95% CI, 1.28-9.26; P=0.015), and higher number of zoledronate infusions (HR=1.07; 95% CI, 1.03-1.11; P=0.001) significantly increased the risk of developing BRONJ.Increased cumulative doses and long-term BP treatment are the most important risk factors for BRONJ development. Type of BP, diabetes, hypothyroidism, smoking, and prior dental extractions may play a role in BRONJ development.

Background: Motexafin gadolinium (MGd) disrupts redox-dependent pathways by inhibiting oxidative stress-related proteins leading to apoptosis. MGd selectively targets tumor cells, disrupting energy metabolism and repair mechanisms, rendering cells more prone to apoptosis. Preclinical studies with MGd and pemetrexed show significant tumor growth delay in lung cancer cell lines. Methods: Patients with non-small cell lung cancer, Eastern Cooperative Oncology Group performance status 0 to 1, who had received one previous platinum containing regimen and normal organ function were treated with MGd 15 mg/kg and pemetrexed 500 mg/m 2 q21days. Patients were allowed to receive more than one regimen if the initial treatment was in the adjuvant or curative setting and administered >12 months earlier. The primary end point was to demonstrate a 40% rate of 6-month progression free survival (PFS). Results: Seventy-two patients (30 women, 42 men), performance status 0/1 (30/42), and a median age of 63 years were enrolled. Most patients (96%) were current or former smokers. All histologic types were represented (squamous/adenocarcinoma/other: 28%, 42%, 31%). Number of prior regimens: 1: 69%; 2: 26%, and >2: 4%. Median number of cycles administered was (range) 2 (1–12). Toxicity: grade 3/4 neutropenia was noted in 8.3% with febrile neutropenia in 1.4%, thrombocytopenia in 8.3%, fatigue in 9.7%, and pneumonia in 11.1%. There were no complete responses, 8.1% had partial response, 56.5% had stable disease, and 35.5% had progressive disease as their best response. Twenty-three percent of patients were progression free at 6 months and the median PFS was 2.6 months with an overall survival of 8.1 months. Conclusions: The combination of MGd and pemetrexed was well tolerated with toxicity similar to that of pemetrexed alone. However, the study did not achieve its end point of 40% 6-month PFS. The response rate, PFS, and overall survival did not seem markedly different than prior phase II and phase III studies of pemetrexed alone. Consequently, there are no further plans for development of this combination.

Purpose/objectives To identify risk factors for lymphedema after breast cancer surgery. Design Multisite case-control study. Setting Lymphedema clinics in the upper midwestern region of the United States. Sample 94 patients with lymphedema and 94 controls without lymphedema, matched on type of axillary surgery and surgery date. Methods The Measure of Arm Symptom Survey, a patient-completed tool, assessed potential risk factors for lymphedema. Severity of lymphedema was measured by arm circumference, and disease and treatment factors were collected via chart review. Main research variables Risk factors for lymphedema after breast cancer surgery. Findings On univariate analysis, patients with lymphedema were more likely than controls to be overweight (body mass index >or= 25) (p = 0.009). They also were more likely to have had axillary radiation (p = 0.011), mastectomy (p = 0.008), chemotherapy (p = 0.033), more positive nodes (p = 0.009), fluid aspirations after surgery (p = 0.005), and active cancer status (p = 0.008). Strength training (p = 0.014) and air travel (p = 0.0005) were associated with less lymphedema occurrence. On multivariate analysis, the only factor significantly associated with lymphedema was being overweight (p = 0.022). Conclusions Being overweight is an important modifiable risk factor for lymphedema. Axillary radiation, more extensive surgery, chemotherapy, and active cancer status also were predictive of lymphedema. Implications for nursing This study provides evidence that excess weight contributes to lymphedema; strength training and airline travel did not contribute to lymphedema.

169 Background: Single-agent durvalumab is being evaluated in patients with advanced squamous and non-squamous NSCLC in an ongoing Phase 1/2 study (NCT01693562). Here we present updated survival and safety data in NSCLC patients. Methods: Treatment-naïve (1L) and previously treated (2L or 3L+) stage IIIB/IV NSCLC patients received durvalumab 10 mg/kg Q2W for up to 12 months. Patients were stratified by tumor PD-L1 expression (Ventana PD-L1 [SP263] Assay [PD-L1 high: ≥25% of tumor cells with membrane staining]), treatment line, and histology. Results: As of 05 September 2017, 304 NSCLC patients received durvalumab monotherapy. Median duration of follow-up was 35.6 (0.3–50.9) months. Investigator-assessed ORR ranged between 23.2% and 30.0% among PD-L1 high patients, and between 3.6% and 8.3% among PD-L1 low/negative patients. Median PFS and median OS were longer in PD-L1 high vs PD-L1 low/negative patients (Table). Any-grade treatment-related AEs (TRAEs) were reported in 57.2% of pts (including fatigue, 17.4%, decreased appetite, 9.2%, diarrhea, 8.9%); in 10.2% of pts these were Grade 3 or 4. TRAEs resulting in treatment discontinuation were reported in 17 patients (5.6%); 1 patient had a Grade 5 TRAE (pneumonia). Conclusions: In this ongoing phase 1 study, OS and safety profile appear encouraging in treatment-naïve and previously treated NSCLC patients, particularly among PD-L1 high patients. Further investigation regarding PD-L1 expression for selection of patients who most likely benefit from durvalumab is needed. Clinical trial information: NCT01693562. [Table: see text]

3531 Background: Nivo, a fully human anti-PD-1 mAb, provided an ORR of 31%, durable responses (median DOR not reached), and a 12-mo OS rate of 73.8% in pts with dMMR/MSI-H mCRC (Overman M, et al. 2017). Preliminary analysis of nivo + ipi, a humanized anti-CTLA-4 mAb, demonstrated manageable safety and promising efficacy in pts with dMMR/MSI-H mCRC (Overman M, et al . 2016). Here we report interim safety and efficacy of nivo + ipi in this pt population from the Checkmate 142 study (NCT02060188). Methods: Pts with dMMR/MSI-H mCRC who progressed on or were intolerant of ≥1 prior line of therapy received nivo 3 mg/kg + ipi 1 mg/kg q3w × 4 doses followed by nivo 3 mg/kg q2w until discontinuation due to disease progression or other reason. Primary endpoint was investigator-reported ORR by RECIST 1.1. Other endpoints included DOR, PFS, OS, safety, and tolerability. Results: 27 pts with dMMR/MSI-H mCRC treated with nivo + ipi received the first dose ≥6 mo prior to the database lock (DBL; Sept 2016). Of these pts, 93% received ≥2 prior lines of therapy. At the time of DBL, 44% of pts remained on treatment, and 14 pts had discontinued therapy due to disease progression (n=8) or TRAEs (n=6). ORR was 41% and disease control rate (DCR) was 78% (Table). The median time to response was 2.7 mo, and 82% of responses (9/11) were ongoing at 6 mo. The medians for DOR, PFS and OS had not been reached. Grade 3–4 TRAEs occurred in 10 pts (37%).TRAEs leading to discontinuation included acute kidney injury, increased transaminases, necrotizing myositis, sarcoidosis, dyspnea, and thrombocytopenia (1 each). No deaths were attributed to therapy. Conclusions: Initial analysis ofnivo + ipi in pts with ≥6-mo follow-up demonstrated a manageable safety profile and clinical activity characterized by a high DCR and encouraging survival benefit. This study is ongoing, and updated efficacy and biomarker analyses of ≈80 pts with ≥6-mo follow-up will be presented. Clinical trial information: NCT02060188. [Table: see text]

Background: MMR or MSI testing is recommended for mCRC pts and is often done locally by IHC or PCR testing, respectively (NCCN V1.2017) Nivo, a fully human anti-PD-1 mAb, demonstrated durable responses and a 12-mo OS rate of 73.8% in pts with mCRC locally assessed for dMMR/MSI-H status in the CheckMate 142 study (NCT02060188; Overman M, et al. 2017). Here we describe the results of local and central testing with respect to MMR/MSI status and clinical outcomes in the CheckMate 142 study. Methods: MMR/MSI status was assessed locally on archival tumor using IHC/PCR at screening and confirmed centrally by PCR (modified Bethesda panel) testing of tumor biopsy at enrollment. dMMR was defined by IHC as a loss of expression in ≥1 mismatch repair proteins. Stable microsatellite (MSS), low MSI (MSI-L), and high MSI (MSI-H), were defined as instability in 0, 1, or ≥2 markers, respectively. Pts with dMMR/MSI-H mCRC who progressed on or were intolerant of ≥1 prior line of therapy received nivo 3 mg/kg Q2W. Results: 74 ptswere dMMR/MSI-H by local testing. Of these pts, 53 (72%) were centrally confirmed as MSI-H, 7 pts had insufficient tissue sample for PCR testing, and 14 pts had a central test that did not match local test results. Of the 14 pts, 3 pts with a clinical history of LS were identified locally as dMMR but centrally as MSS (Table). INV-reported ORR was 31.1% in 74 pts locally determined as dMMR/MSI-H, 35.8% in 53 pts locally and centrally confirmed as MSI-H, and 21.4% in 14 pts not centrally confirmed as MSI-H. Conclusions: The similar clinical activity between pts locally confirmed as MSI-H and pts who were centrally confirmed as MSI-H suggest local testing is appropriate for identifying the dMMR/MSI-H pts who may benefit from nivo monotherapy. Clinical trial information: NCT02060188. Pt Local Testing Central Testing Clinical History of LS Method Result 1 IHC dMMR MSS NA 2 IHC dMMR MSS No 3 IHC dMMR MSS Yes 4 IHC dMMR MSS Yes 5 IHC/PCR dMMR (IHC)/MSI-H (PCR) MSS NA 6 IHC dMMR MSS Yes 7 IHC dMMR MSS No8 PCR MSI-H MSS NA 9 IHC/PCR dMMR (IHC)/MSI-H (PCR) MSS NA 10 IHC dMMR MSS No 11 IHC dMMR MSS NA 12 PCR MSI-H MSS NA 13 IHC dMMR MSI-L NA 14 IHC dMMR MSS NA NA = not available.

359 Background: GA, FOLFIRINOX and FOLFIRI are standard chemotherapy (CTX) regimens for mPC.The optimal introduction of these regimens following GA is not known. This phase II study evaluated 2 different approaches to this question. Methods: Eligibility criteria included 1) untreated mPC, 2) ECOG PS 0/1, 3) organ function adequate for Rx. Patients (pts) were treated according to one of 2 methods following GA given per standard dose/schedule: FOLFIRINOX (bolus 5-FU omitted) for up to 12 cycles at 24 weeks or at time of disease progression (S); or GA alternating with FOLFIRI q8 weeks up to 48 weeks total Rx (A). Results: 54 evaluable pts (28S, 26A) were enrolled . Pt characteristics included median age 65, M/F 48/52% , liver involvement 89%. 17/53 pts (31%) did not achieve disease control at 8 weeks (8 toxicity/complications , 6 disease progression, 3 declined further protocol therapy). Of the remaining 37 pts, 24/13 were treated with S/A regimens, respectively. Grade ≥ 3 treatment toxicities reported while on study with frequency ≥ 10% included anemia 21%, neutropenia 43%, thrombocytopenia 15%, and fatigue 22%. Grade ≥ 3 neuropathy occurred in 8% of pts. For all 54 pts using RECIST 1.0, CR/PR/SD/DC was 2 (4%)/20 (37%)/19 (35%)/41(76%). Ca19.9 response ≥ 90% was seen in 20/37 (54%). For all pts, median OS was 12.3 months ( 95% CI 8.6-14.5 mo); 12 and 24 mo OS was 51% and 11%, respectively. For the 37 pts with DC on GA at 8 weeks (calculated from start Rx) median OS was 13.5 mo (95% CI 10.7-15.4 mo); 12 and 24 mo OS was 55% and 16% , respectively. No statistically significant differences were seen between S and A with respect to toxicity, response or survival. Conclusions: 1) As opposed to introduction of 5FU-based CTX at the time of disease progression/prohibitive toxicity, introduction prior to that time may be at least comparable regarding both toxicity and OS. 2) This approach may further enhance OS in pts who achieve DC on GA at 8 weeks. 3) Neither S nor A method of 5FU-based CTX introduction following GA was clearly superior in this study. 4) How best to combine 5FU-based combination CTX following GA in mPC merits further study. Supported by the Seena Magowitz Foundation.

279 Background: Tarextumab (TRXT), fully human IgG2 antibody inhibits signaling of Notch2/ 3 receptors. Tumor regression seen in Notch3 (N3) expressing pt-derived pancreatic cancer xenografts when TRXT combined with Nab-P+Gem. Phase 2, randomized, placebo-controlled trial conducted to evaluate efficacy, safety of combination in mPC. Methods: Pts randomized 1:1 to TRXT or placebo (PL). TRXT given IV at 15 mg/kg q 2wks (D 1, 15), nab-P 125 mg/m2, GEM 1000mg/m2 on D1, 8, 15 q 28 days. Tissue for N3 gene expression determination was required. Primary endpoints: overall survival (OS) in all and in 3 subgroups determined by Notch 3 gene expression. Secondary: safety, progression-free survival (PFS) and overall response rate (ORR). Results: N = 177 pts randomized. Performance status (0 or 1), CA19-9 stratum (0 – ULN, > ULN – 59ULN, ≥ 59ULN) balanced. Clinical trial information: NCT01647828. . Conclusions: Addition of TRXT to Nab-P+Gem did not improve OS in 1st line mPC. A potential detrimental effect on PFS and ORR was seen in subjects with N3 < 25%ile.[Table: see text]

3055Background: Avelumab* is a fully human anti-PD-L1 IgG1 antibody showing preliminary efficacy in multiple tumor types. We report updated safety data of single-agent avelumab in patients (pts) wi...

Radon is the second leading cause of lung cancer and it is recommended that all homes be tested for radon. Written surveys completed by 692 patients at two primary care clinics in the Minneapolis, MN, area revealed that only 24.7 % had ever tested their home. Testing rate was higher with greater income and education level and in homes without someone who smokes. Of participants whose homes had not been tested, 250 were enrolled in an intervention that included printed information on radon, a coupon for a discounted testing kit, and encouragement by their primary care provider to test. Follow-up indicated minimal effect of this intervention, with only 14.4 % of these participants testing during the ensuing year. Future studies should assess a stronger intervention, perhaps over multiple visits, and providing test kits on site. Targeting patients who smoke may be an effective use of resources.

Cancer risk assessment is an important decision-making tool for women considering irreversible risk-reducing surgery. Our objective was to determine the prevalence of BRCA testing among women undergoing bilateral prophylactic mastectomy (BPM) and to review the characteristics of women who choose BPM within a metropolitan setting.We retrospectively reviewed records of women who underwent BPM in the absence of cancer within 2 health care systems that included 5 metropolitan hospitals. Women with invasive carcinoma or ductal carcinoma in situ (DCIS) were excluded; neither lobular carcinoma in situ (LCIS) nor atypical hyperplasia (AH) were exclusion criteria. We collected demographic information and preoperative screening and risk assessment, BRCA testing, reconstruction, and associated cancer risk-reducing surgery data. We compared women who underwent BRCA testing to those not tested.From January 2002 to July 2009, a total of 71 BPMs were performed. Only 25 women (35.2%) had preoperative BRCA testing; 88% had a BRCA mutation. Compared with tested women, BRCA nontested women were significantly older (39.1 vs. 49.2 years, P 0.001), had significantly more preoperative biopsies and mammograms and had fewer previous or simultaneous cancer risk-reducing surgery (oophorectomy). Among BRCA nontested women, common indications for BPM were family history of breast cancer (n = 21, 45.6%) or LCIS or AH (n = 16, 34.8%); 9 nontested women (19.6%) chose BPM based on exclusively on cancer-risk anxiety or personal preference.Most women who underwent BPM did not receive preoperative genetic testing. Further studies are needed to corroborate our findings in other geographic regions and practice settings.

We present a case of a patient who developed all manifestations of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) acutely following treatment of cutaneous T-cell lymphoma (CTCL, Sezary syndrome) with deoxycoformycin (pentostatin). Symptoms and signs included severe thrombocytopenia and microangiopathic hemolytic anemia; hallucinations, confusion and disorientation; oliguric acute renal failure requiring hemodialysis; and fever. No other etiology for these symptoms and signs was present. Complete recovery followed treatment for one month with plasma exchange and glucocorticoids. During the succeeding 20 months she has remained well and her CTCL remains stable on no further treatment. This case and two previously published cases suggest that acute and severe TTP-HUS may be a dose-dependent toxicity of deoxycoformycin (pentostatin).

To report the clinical features, risk factors, management, and treatment outcomes of nitrogen-containing bisphosphonate (n-BIS)-related osteonecrosis of the jaw (BRONJ).Patients with suspected BRONJ were referred to the School of Dentistry for evaluation and treatment.A total of 26 patients (9 men and 17 women, mean age 64 years) were diagnosed with BRONJ. Of the 26 patients, 23 had received n-BIS therapy for cancer and 3 for osteoporosis. BRONJ lesions were noted more frequently in the mandible and in the posterior sextants. Of the 26 patients, 16 had developed BRONJ after dentoalveolar procedures, and 10 had developed it spontaneously. The mean interval to development of BRONJ was shorter in the patients with cancer receiving intravenous n-BIS than in the patients with osteoporosis receiving oral n-BIS (37.1 versus 77.7 months, P = .02). Using the American Association of Oral and Maxillofacial Surgeons staging system, 2 patients were diagnosed with stage I lesions, 19 with stage II, and 5 with stage III lesions. The initial management of BRONJ was nonsurgical, with debridement performed at subsequent visits, if needed. The BRONJ lesions healed completely in 4 patients, healed partially in 8, remained stable in 7, and progressed in 7. The spontaneous lesions responded favorably to BRONJ management compared with lesions that developed after dentoalveolar procedures (P = .01). No significant difference was found in response to BRONJ management between patients who had continued or discontinued n-BIS therapy after the BRONJ diagnosis (P = .54).Long-term n-BIS therapy and recent dental procedures are consistent findings in patients with BRONJ. Spontaneous BRONJ lesions respond favorably to current BRONJ treatment strategies.

Background: Burkitt lymphoma (BL) is a highly aggressive B-cell lymphoma that is largely curable with intensive therapy. Previously, a single-center study of 30 patients demonstrated that DA-EPOCH-R based therapy was highly effective in adults with BL (N Engl J Med 2013; 369:1915-1925). We set out to validate these results in a multi-center study and assess if a risk-adapted approach using DA-EPOCH-R is effective. Methods: Patients had newly diagnosed BL, age 18 years or older and HIV negative or positive. Low-risk (LR) patients (normal LDH, ECOG P.S. 0-1, stage I or II disease and a maximum tumor size < 7cm) received 3 cycles of DA-EPOCH-R (with no intrathecal prophylaxis) and all other patients (classified as high risk (HR)) received 6 cycles (with IT prophylaxis days 1 and 5 on cycles 3-6). Results: 77 patients were enrolled. Characteristics include median (range) age 45 (19-78) years; male sex 63 (82%); stage III or IV disease 49 (64%); elevated LDH 41 (53%); CNS involvement 7 (10%); HIV positive 20 (26%). Eleven (14%) and 66 (86%) were classified as LR and HR respectively. There were 2 deaths on treatment in the HR arm secondary to infection. Other toxicities were similar to previous reports of DA-EPOCH-R. At a median follow-up time of 25 months, time to progression (TTP), progression-free survival (PFS) and overall survival (OS) were 92% (95% CI: 82.9-96.8%), 87% (95% CI: 76.2-93%) and 88% (95% CI: 77.1-93.8%) respectively for all patients. TTP, PFS and OS were not significantly different for HR versus LR disease, HIV positive versus negative and age over versus under 40y. Conclusions: In a multicenter setting, both LR and HR patients have excellent outcomes with 3 and 6 cycles of therapy respectively. Risk group, HIV status and age are not associated with outcome (see table). Accrual to this study continues ([NCT01092182][1]). | | | TTP | PFS | OS | | ------------------------------------------- | ------------- | ------------------------------ | ------------------------------ | ------------------------------ | | Patients | N=77 | 92% | 87% | 88% | | LR HR p | 11 66 | 100% 91% 0.35 | 100% 85% 0.22 | 100% 86% 0.24 | | HIV - HIV + p | 57 20 | 96% 84% 0.1 | 88% 84% 0.66 | 90% 83% 0.53 | | Age under 40 Age over 40 p | 35 42 | 94% 91% 0.83 | 90% 84% 0.45 | 93% 83% 0.24 | Table. ![Figure 1.][2] Figure 1. Disclosures Link: Genentech: Consultancy, Research Funding; Kite Pharma: Research Funding. Kahl: Roche/Genentech: Consultancy; Seattle Genetics: Consultancy; Millennium: Consultancy; Cell Therapeutics: Consultancy; Celgene: Consultancy; Infinity: Consultancy; Pharmacyclics: Consultancy; Juno: Consultancy. Bartlett: Gilead: Consultancy, Research Funding; Janssen: Research Funding; Pharmacyclics: Research Funding; Genentech: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Millennium: Research Funding; Colgene: Research Funding; Medimmune: Research Funding; Kite: Research Funding; Insight: Research Funding; Seattle Genetics: Consultancy, Research Funding; MERC: Research Funding; Dynavax: Research Funding; Idera: Research Funding; Portola: Research Funding; Bristol Meyers Squibb: Research Funding; Infinity: Research Funding; LAM Theapeutics: Research Funding. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01092182&atom=%2Fbloodjournal%2F126%2F23%2F342.atom [2]: pending:yes

Background: Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE) is the largest registry of prospectively treated PTCL patients in the United States. Patients are enrolled at the initial diagnosis of PTCL and within 30 days of starting treatment. Data on demographics, clinical characteristics, diagnosis, therapy delivered as induction or salvage, and outcomes are collected. Methods: For this report, we examined baseline characteristics and induction treatment patterns for patients with the 3 most common subtypes of PTCL: PTCL not otherwise specified (NOS), anaplastic large cell lymphoma (ALCL) and angioimmunoblastic T-cell lymphoma (AITL). Only data from locked records are reported. Locked records are those that have been reviewed and digitally signed by the treating investigator. Results: Five hundred patients were enrolled from February 2010 until January 2014. As of July 2014, there were 257 locked baseline records and 188 locked treatment records for patients with a diagnosis of PTCL-NOS, ALCL or AITL. The mean age of these patients was 60 (range: 51-70). Most were male (66%) and white (78%). At study entry, 234 (91%) had an ECOG performance status of 0-1, 190 (74%) had Ann Arbor stage of III/IV, and 120 (47%) had one or more B symptoms. Half of the patients had extranodal disease. Mean international prognostic index (IPI) score was 2 (range 0-5). For staging, a PET/CT was the most common radiographic method used (58% of patients), and for pathologic diagnosis, on average, 10 phenotypic and ~1 genetic markers were assessed. For baseline characteristics reported here, patients treated at academic centers had more extranodal disease, a higher IPI score and tended to have more advanced disease compared to patients treated in the community. The primary intent of initial therapy was a cure for 89% of patients and 60% received an anthracycline or anthracycline plus etoposide-containing regimen. A minority of patients (21%) participated in a clinical trial for PTCL. Further details on induction therapy can be found in the table below. Table Initial Treatment Characteristics Total Academic Community Initial Treatment Approach* N=188 n=158 n=30 Induction chemotherapy (CT) alone 125 (66%) 102 (65%) 23 (77%) Induction CT + consolidation or maintenance 11 (6%) 10 (6%) 1 (3%) Stem cell transplant 36 (19%) 33 (21%) 3 (10%) Local radiotherapy +/- chemotherapy 10 (5%) 7 (4%) 3 (10%) Observation/best supportive care 6 (3%) 6 (4%) 0 (0%) Induction Regimens N=186 n=154 n=32 CHOP/CHOP-like 76 (41%) 56 (36%) 20 (63%) CHOP/CHOP-like + etoposide 37 (20%) 30 (20%) 7 (22%) Gemcitabine-based regimen 6 (3%) 6 (4%) 0 (0%) Platinum-based regimen 5 (3%) 5 (3%) 0 (0%) Other 62 (33%) 57 (37%) 5 (15%) Number of Cycles of Induction CT Median, Inter-Quartile Range (Cycles) 5 (2-6) 5 (2-6) 5 (1-6) Type of Transplant Performed N=36 n=33 n=3 Autologous 34 (94%) 31 (94%) 3 (100%) Allogeneic 2 (6%) 2 (6%) 0 (0%) *5 patients received CNS prophylaxis with selected treatments shown above CHOP=cyclophosphamide, doxorubicin, prednisone, and vincristine Conclusions: Early results from the first prospective US-based registry of newly diagnosed patients with PTCL-NOS, ALCL and AITL show that beyond CHOP-based therapy, there is little consensus on initial management of these patients. These data strongly support the need to develop evidence-based approaches for this rare and heterogeneous group of patients. Disclosures Pinter-Brown: Spectrum: Consultancy, Membership on an entity's Board of Directors or advisory committees. Foss:spectrum: Research Funding; seattle genetics: Research Funding; Merck: Research Funding; Celgene: Honoraria, Research Funding; Millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Carson:Spectrum: Consultancy; Celgene: Consultancy, Speakers Bureau. Horwitz:Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Spectrum: Research Funding; Infinity: Research Funding; Kiowa-Kirin: Research Funding; Amgen: Consultancy; Bristol-Myers Squibb: Consultancy. Rosen:Allos: Consultancy, Honoraria. Gisselbrecht:Spectrum: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hsi:Daiichi-Sankyo: Consultancy; Allos: Research Funding; Seattle Genetics: Speakers Bureau; Eli Lilly: Research Funding; Abbott: Research Funding; Cellerant Therapeutics: Research Funding; BD Biosciences: Research Funding; Millennium: Research Funding. Advani:Seattle Genetics: Research Funding. Lechowicz:Spectrum: Consultancy; Seattle Genetics: Consultancy; Janssen: Consultancy; Millennium: Consultancy. Smith:Allos/Spectrum: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kahl:Allos : Research Funding. Park:Teva: Research Funding; Seattle Genetics: Research Funding; Janssen: Travel funding, Travel funding Other.

e19018 Background: CX is a fully human IgG1 monoclonal antibody to the insulin-like growth factor type receptor 1 (IGF1R) that can potentially reverse resistance and enhance treatment efficacy. E35...

224 Background: FOLFIRINOX or NabP-Gem are now standard mPC regimens.The optimal sequence is not known.This phase II study evaluated the feasibility of NabP-Gem followed by FOLFIRINOX. Methods: Eligible pts had evidence of untreated mPC, ECOG 0-1 and adequate organ function. Pts received Nab-P (125 mg/m2) and Gem (1000 mg/ m2) weekly x 3 (Induction ) every 4 weeks for upto 6 cycles. FOLFIRINOX, q2 weeks (Consolidation regimen) was initiated after 6 cycles of the Induction regimen, or earlier in case of progression, and given for a maximum of 6 months (12 cycles). mFOLFIRINOX (NEJM, 364:1817-25: 2011) has been modified with growth factor prophylaxis and omission of bolus 5FU. One endpoint is to increase 1 year survival to > 70%, (n=30, 95% CI is +/- 20%). Results: Accrual goals have been met (n=31). The M/F ratio is 55%/45%, median is 66 years. In 23 pts with elevated baseline CA19-9 levels treated with NabP-Gem, 83% had a > 90% decrease. The response rate with the NabP-Gem regimen is 43%. Selected therapy related Grade > 3 adverse events during the course of both NabP-Gem and FOLFIRINOX therapy are: neutropenia (39%), fatigue (32%), anemia (19%), thrombocytopenia (16%), thromboembolic events (3%), peripheral neuropathy (16%), leukopenia (16%), nausea (3%), vomiting (3%), diarrhea (7%), and neutropenic fever (3%). During the course of NabP-Gem, 14 dose reductions and four dose delays were seen. Two pts had early progression at cycle 4 or less and were switched to the Consolidation regimen. Seventy one % (22/31) of pts went on to receive FOLFIRINOX (4 pts still on study), 4 received FOLFIRI, and one pt received FOLFOX as Consolidation therapy. One-year survival is projected to be 50-60%. Conclusions: The induction NabP-Gem regimen shows evidence of substantial activity similar to published reports (JCO.29:4548-54: 2011). The induction-consolidation strategy is feasible in selected patients. Cumulative side effects predominantly fatigue and neuropathy will require appropriate dose reductions or treatment breaks. (Supported by the Seena Magowitz foundation). Clinical trial information: NCT01488552.

1129 Background: Microinvasive breast cancer (Tmic) is defined by the AJCC as extension of cancer cells beyond the basement membrane with no single focus larger than 1 mm. The clinical behavior of this entity is unclear. Most series suggest that prognosis is similar to non-invasive cancer although the literature is mixed. Surgical management typically reflects invasive breast cancer including lymph node sampling. Published incidence of nodal involvement is also variable with some small series reporting incidence as high as 20%. We present a clinicopathologic review of a large series from a community practice setting. Methods: Using the AJCC definition of Tmic, we retrospectively identified all cases treated within Allina Health System from 2001-2011. Inclusion criteria included no prior history of breast cancer and available follow-up data. Data collected included ER/PR and HER2 status (when available), margin status and surgical and adjuvant therapy. Results: 118 eligible cases were identified with a mean follow-up of 3.65 years and mean age of 56.8 years (34-88). 39 were triple negative and 29 were HER2+. ER/PR data was available on all cases, HER2 on 60. 72 were treated with mastectomy. All patients underwent axillary staging. Lymph node metastasis was identified in 2 cases (one triple negative, one HER2+). In one case the metastasis measured 0.25 mm, in the other 0.4 mm. Complete axillary dissection performed on both cases demonstrated no additional lymph node involvement. Isolated tumor cells were also identified in 9 cases. 2 cases developed local recurrence following lumpectomy and radiation, both in the ipsilateral breast. One recurred with microinvasive disease, the second with DCIS only. There were no cases of metastatic recurrence and no breast cancer associated deaths. Conclusions: The clinical behavior of microinvasive breast cancer in this series is similar to DCIS. The incidence of lymph node metastasis was low (1.7%) and there were no cases of distant metastasis. Our data supports management of microinvasive breast cancer as a subset of DCIS and suggests that the benefit of routine lymph node sampling is questionable.

Abstract 430 Background: Inotuzumab ozogamicin (CMC-544) is a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic antitumor antibiotic that binds DNA (producing double stranded DNA breaks). CD22 is expressed in the majority of B-cell non-Hodgkin lymphomas (NHL), and inotuzumab ozogamicin monotherapy has demonstrated efficacy and tolerability in heavily pretreated patients. Thus, inotuzumab ozogamicin monotherapy is being further investigated in patients with indolent B-cell NHLs that are refractory to rituximab alone, rituximab in combination with chemotherapy, or radioimmunotherapy (RIT). Objectives: To evaluate the safety and efficacy of inotuzumab ozogamicin in patients with indolent B-cell NHL who have relapsed or are refractory to rituximab and chemotherapy, or anti-CD20 radioimmunotherapy (RIT) as measured by overall response rate (ORR), complete response (CR) rate, duration of response (DR), progression-free survival (PFS), and overall survival (OS). Methods: Patients are eligible for this trial if they have CD22-positive indolent B-cell NHL (defined as follicular not transformed, marginal zone and small lymphocytic lymphoma [SLL]) that has progressed after 2 or more systemic therapies, and have exhibited no response or progressed within 6 months from completion of the most recent rituximab or rituximab-containing therapy, or within 12 months of the completion of RIT. Patients receive inotuzumab ozogamicin at1.8 mg/m2 every 28 days for 4 to 8 cycles, with dose and/or frequency adjusted based on toxicities. Results: We report preliminary data for 43 patients, including 35 patients with follicular, 3 with marginal zone and 3 with SLL, and with a median duration of follow-up of 4.5 months (range 1.0–10.0). Median age was 62 years (range 45–84), and 42% were male. 8% had 1 prior anticancer regimen, 33% had 2, 18% had 3, 43% had 4 or more. Based on the Follicular Lymphoma International Prognostic Index, 12%, 29%, and 59% of the follicular lymphoma patients were low, intermediate, and high risk, respectively. The most common (≥20%) treatment-emergent adverse events (AEs), all grades, were thrombocytopenia (65%), neutropenia (53%), elevated AST (48%), leukopenia (40%), nausea (40%), fatigue (35%), lymphopenia (35%), decreased appetite (33%), and elevated alkaline phosphatase (25%). Common grade 3/4 AEs (>5% of subjects) were all hematologic (thrombocytopenia [48%], neutropenia [28%], lymphopenia [12.5%]). Eight serious AEs (SAEs) have been reported, including 2 cases of pyrexia, and single events of hydronephrosis (known lymphoma) leading to sepsis and death, upper abdominal pain (suspected splenic infarct), pneumonia, abdominal distension, urinary retention, and abnormal hepatic function. Eleven (26%) patients discontinued treatment due to AEs, mostly laboratory abnormalities that failed to recover to grade 1 or better within the protocol-specified allowed dose delay period, including 7 (18%) due to thrombocytopenia, 4 (10%) due to neutropenia, and 1 patient each due to increased GGT, decreased platelet count, hyperbilirubinemia, and pneumonia. An ORR of 53% has been observed, with an ORR of 66% in follicular lymphoma patients. Seven patients (19%) achieved a CR. Of the 11 patients who discontinued treatment early due to AEs (with a median number of cycles received 2), 8 (73%) attained a clinical response. PFS rate at 6 months was 0.59 (95% CI 0.38, 0.75), with a PFS rate at 6 months for follicular lymphoma patients of 0.67 (95% CI 0.44, 0.83). Three deaths have been reported, due to disease progression, sepsis, and aspiration pneumonia (non-neutropenic), respectively, and all >30 days from the last dose of inotuzumab ozogamicin. Conclusion: Inotuzumab ozogamicin in this indolent B-cell NHL patient population has a similar safety profile to that previously reported for monotherapy, with hematologic, gastrointestinal and hepatic laboratory abnormalities being the most common. Inotuzumab ozogamicin monotherapy demonstrates definite clinical activity in indolent B-cell NHL that is refractory to rituximab alone, rituximab in combination with chemotherapy, or RIT. Disclosures: Goy: Allos Therapeutics: Consultancy, Honoraria; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hua:Pfizer: Employment, Equity Ownership. Volkert:Pfizer: Employment, Equity Ownership. Vandendries:Pfizer Inc.: Employment, Equity Ownership.

e18086 Background: S is an oral TKI which affects multiple pathways including VEGFR and PDGFR. Angiogenesis appears to play an important role in the biology of SCLC making it an attractive target for therapy. The only approved therapy for relapsed SCLC in the US is T which has no overlapping toxicities with S. Combining these strategies is a rational approach to treating SCLC although there is no reported data on the combination. Methods: We enrolled pts with relapsed or refractory SCLC previously treated with platinum containing chemotherapy. T was administered at 4 mg/m2 weekly × 3 every 28 days and S was administered in a 3+3 dose escalation design. The planned dose levels were 200 mg qd, 200 mg bid and 400 mg bid. Hematologic toxicity was not considered a S DLT and T dose modifications were planned to address this. Results: 16 pts were enrolled. 3 patients were treated in each of the first 2 dose levels with no DLT seen. 10 patients were treated at the 400 mg bid dose level. 3 DLTs were seen (1 grade ...

e18040 Background: Previous studies have suggested improved outcomes with a single topoisomerase I inhibitor for chemotherapy naive advanced non-squamous non-small cell lung (NSCLC). Bevacizumab is...

6569 Background: At least 13 articles, including 5 in the Journal of Clinical Oncology, have reported low rates of mammography in breast cancer survivors. In studies analyzing the first 12 to 18 months following breast cancer diagnosis and/or treatment, mammography rates were typically between 70% and 80%. Analyses of administrative data at our institution, Park Nicollet Health Services (PNHS), showed the same result despite oncologists' insistence that they were diligent about this aspect of follow-up care. Method: Using the PNHS Cancer Registry, we identified 191 women diagnosed with non-metastatic breast cancer at PNHS in 2001 who allowed their records to be used for research, were alive as of January 15, 2007, and received cancer care and primary care within PNHS. We used the PNHS administrative (claims) database to determine whether each woman received mammography during the year following active breast cancer treatment, and we used the PNHS electronic medical record to review charts of women who acc...