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Background: Hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (Her2-) breast cancers represent the majority of metastatic breast cancers (mBC) among women and are often treated with sequential courses of endocrine therapy (ET) prior to the eventual need for chemotherapy (CT). Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) block cell cycle progression and decrease proliferation of breast cancer cells. Currently, there are three available CDK4/6i: palbociclib, ribociclib and abemaciclib. Each has been shown to improve progression-free survival (PFS) when given with ET in the frontline setting, compared to ET alone. After progression on CDK4/6i, no standard of care exists for the next line of systemic therapy, and there are no prospective data to help guide clinical practice. Analysis of real-world data may provide insight into optimal second-line treatment for women who have progressed on CDK4/6i therapy. Methods: The nationwide Flatiron Health electronic health record-derived de-identified database was utilized for this analysis. We evaluated patient data collected from 2015-2020 for women with HR+/Her2- mBC who received CDK4/6i as frontline therapy and received a documented second-line systemic therapy. The objectives of this study were to describe what therapies were given as second-line treatment and estimate the real-world PFS (rwPFS) of those therapies. rwPFS was defined as time between initiation of second-line therapy until clinician-recorded progression (or death). Patients (pts) who did not progress or die were considered censored at the end of follow-up or end of second-line therapy. Results: A total of 1,210 pts with HR+/Her2- mBC received CDK4/6i with ET in the frontline setting, including 29.1% with de novo metastatic disease. Average age at diagnosis of metastatic disease was 64.4 years (range 28-84). A majority of pts received palbociclib in the frontline setting (88.2%), and 68.8% received an aromatase inhibitor (AI) as the frontline ET partner. 839 pts subsequently received second-line therapy (Table 1). CDK4/6i was continued as part of second-line treatment in 308 (36.7%) pts. 249 (29.7%) pts received CT as second-line treatment. The proportion of pts who continued CDK4/6i increased from years 2015-2020 (p=0.035), and the proportion who received CT decreased over time (p TABLE 1. Second-Line Therapy Used. F, fulvestrant; T, tamoxifenSECOND-LINE THERAPYOverall (N=839)AI23 (2.7%)CDK4/6i4 (0.5%)CDK4/6i + AI97 (11.6%)CDK4/6i + F160 (19.1%)CDK4/6i + F + AI35 (4.2%)CDK4/6i + F + T3 (0.4%)CDK4/6i + T3 (0.4%)CT249 (29.7%)F70 (8.3%)F + AI14 (1.7%)mTOR99 (11.7%)PARP4 (0.5%)PI3K16 (1.9%)T11 (1.3%)Clinical Trial51 (6.1%) Citation Format: James M Martin, Elizabeth A Handorf, Alberto J Montero, Lori J Goldstein. Analysis of systemic therapies following progression on frontline CDK4/6-inhibitor therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-15.

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.

e13034 Background: Current ASCO guidelines recommend endocrine therapy as preferred primary treatment for hormone receptor positive (HR+) metastatic breast cancer (MBC). We assessed survival outcomes of HR+/HER2- MBC patients undergoing endocrine therapy with and without chemotherapy. Methods: The National Cancer Database was queried 2004-2016 for patients with de novo HR+/HER2- MBC. Exclusion criteria were treatment with surgery or radiation at the primary site and missing oncologic and follow up data. Overall survival was compared between systemic treatment groups using multivariable cox proportional hazards regression modes. Results: 19,317 patients met inclusion criteria, among whom 2,360 (12%) received no systemic therapy, 2,617 (14%) received chemotherapy only, 10,078 (52%) received endocrine therapy only and 4,262 (22%) received both chemotherapy and endocrine therapy. Patients treated with chemotherapy only more frequently had lung (38%, p

e13054 Background: Conflicting data exist regarding benefit of surgery of the primary site for stage IV breast cancer, in which systemic therapy is standard of care and patient characteristics may bias treatment decisions. Metastatic triple negative breast cancer (TNBC) is an aggressive subtype with limited therapy options and poor prognosis. Our aim was to assess whether surgery for the primary tumor in stage IV TNBC provides a survival advantage over systemic therapy alone. Methods: The National Cancer Database was queried for patients with de-novo stage IV TNBC who received systemic therapy alone or systemic therapy and surgery of the primary breast site 2004-2016. Patients receiving surgery for metastatic tumor sites or with incomplete follow up data were excluded. 1:1 propensity matching was performed for demographics, comorbidities, clinical T and N stage, and metastatic sites to minimize confounding factors. Survival outcomes were analyzed using a stratified log-rank test and Cox proportional hazard regression analysis. Results: Of 2989 patients, 782 (26.21%) underwent surgery plus systemic therapy and 2207 (73.84%) were treated with systemic therapy alone. The majority of all patients were aged 51-70 with low co-morbidity, and treated in metropolitan areas. Patients treated at academic facilities (OR = 0.67, p = 0.025), with multiple metastatic sites (OR = 0.59, p < 0.001), or advanced clinical N stage (OR = 0.55, p < 0.001) were less likely to undergo surgery. Of those who completed surgery, 58% had unilateral mastectomy, and 63% had axillary lymph node dissection. Propensity matching identified 507 ‘paired’ patients with similar characteristics in the surgery and systemic therapy alone groups. After multivariable adjustment, surgery was associated with superior overall survival compared with systemic therapy alone (HR 0.73, P < 0.001). Older age (HR = 1.47, p < 0.001), greater comorbidity (HR = 1.28, p < 0.001) and multiple metastatic sites (HR = 1.53, p < 0.001) significantly decreased overall survival in the matched cohort. Median survival was shortest in the systemic therapy alone group (12.8 months, 95% CI 11.3-14.5) and longest in those undergoing systemic therapy plus simple mastectomy (18 months, 95% CI 14.3-21.2), though approximately 4 months of median survival was added for all patients undergoing any surgery vs. systemic therapy alone (p = 0.0001). Conclusions: In stage IV TNBC, surgical resection of the primary tumor site in addition to systemic therapy may provide a survival benefit in selected patients. Though in this retrospective study the sequence of treatment was unknown, surgery could be considered for low disease burden as in other malignancies with oligometastatic disease. Additional research is needed to determine if these findings persist in prospective studies and for other hormone-receptor subtypes.

Introduction Cytomegalovirus (CMV) reactivation remains a common cause of morbidity and mortality following allogeneic hematopoietic cell transplant (HCT) despite attempts at prophylaxis. Following transplantation, surveillance of the peripheral blood CMV viral load with early aggressive treatment is commonly employed and has been an effective strategy at preventing overt infection. While a matched related donor (MRD) is often the preferred transplant type, the use of alternative donors including matched unrelated donors (MUD), mismatched unrelated donors (MMUD) and haploidentical (HI) transplants, has greatly increased over the past several years. The data regarding CMV infection among these alternative donor types is scarce. Objectives To better characterize the extent and risk factors for CMV reactivation among patients who received an allogeneic HCT for hematologic malignancies, particularly among HI transplant recipients and those who received post-transplant high-dose cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis. Methods A retrospective analysis was performed on 88 adults with hematologic malignancies who received an allogeneic HCT at our institution from 2012-2017. Only cases with CMV seropositive donors and/or recipients were included. We compared donor types/sources, conditioning regimens, GVHD prophylaxis regimens, and assessed for CMV reactivation utilizing the peripheral blood polymerase chain reaction (PCR) values that are monitored in post-transplant clinic visits. Results Nineteen (22%) patients received MRD transplants, while the remainder received alternative donor sources, including 17 (19%) HI transplants. Overall, the rate of CMV reactivation was 27% with a significant difference noted between donor sources (p= Conclusion HI HCT transplant recipients are at high risk for CMV reactivation. The use of myeloablative conditioning regimens or PTCy did not affect the rate of CMV reactivation.