Abstract OT1-02-04: SWOG S1418/NRG -BR006: A randomized, phase III trial to evaluate the efficacy and safety of MK-3475 as adjuvant therapy for triple receptor-negative breast cancer with > 1 cm residual invasive cancer or positive lymph nodes (>pN1mic) after neoadjuvant chemotherapy

Abstract

Abstract Background: Patients with residual cancer after neoadjuvant chemotherapy, particularly triple negative cancers (TNBC), have poor prognosis.The SWOG S1418 / NRG BR-006 (NCT02954874) randomized, phase III trial tests the hypothesis that administration of pembrolizumab after surgery for 12 months will reduce invasive disease-free survival (IDFS) by 33% compared to observation in patients with TNBC and > 1 cm residual invasive cancer or positive lymph nodes (>pN1mic) after neoadjuvant chemotherapy. Methods: Eligible patients ≥18 years old with triple negative breast cancer defined by ASCO/CAP guidelines and >1 cm residual invasive cancer in the breast, or any macrometastases in the lymph nodes after completion of 16-24 weeks of neoadjuvant chemotherapy. Patients may receive post-operative chemotherapy for up to 24 weeks but must be registered for screening within 35 days of completion of adjuvant chemo. Completion of radiation therapy prior to registration is allowed, but it is preferred that patients receive radiation after randomization; patients randomized to pembrolizumab will receive their XRT concomitant with pembrolizumab. Adequate organ functions: ANC > 1.5, PLT > 100, Hgb > 9, normal creatinine, Tbili < 1.5 IUNL, AST/ALT/AlkPhos < 2.5 IULN. HIV with good CD4 count is allowed. Active autoimmune disease, Hep B,C, prior immunotherapy, active immunosuppressive therapy, or live vaccines within 30 days of registration are not allowed. Five unstained slides for PDL1 staining are required for stratification. The study has a dual primary endpoint; comparison of IDFS between arms in (i) all randomized patients (1-sided a=0.01) and in PDL-1 positive patients (1-sided a=0.015). Secondary endpoints include toxicity, overall survival, distant recurrence free survival (DRFS) and quality of life measures. Patients will be randomized 1:1 with stratification for PDL1 status, T size, nodal status and adjuvant chemo (yes or no) to observation or 1 year of pembrolizumab 200mg IV q 3 weeks. The accrual goal is N=1000 patients with estimated trial duration of 8 years. Two interim analyses are planned for all randomized patients when 50% and 75% of IDFS events have occurred for early stopping for either futility or efficacy. The study was activated on 11/15/16 and 34 patients were registered as of June 9, 2017. Cancer Trials Support Unit (CTSU) sites can use “OPEN” (https://open.ctsu.org) to enroll patients to this trial. Funding: NIH/NCI U10CA180888, U10CA180819, CA180868; and in part by Merck, Sharpe & Dohme, Corporation. Citation Format: Pusztai L, Barlow WE, Ganz PA, Henry NL, White J, Jagsi R, Mammen JMV, Lew D, Mejia J, Karantza V, Aktan G, Sharon E, Korde L, Hortobagyi GN, Mamounas E. SWOG S1418/NRG -BR006: A randomized, phase III trial to evaluate the efficacy and safety of MK-3475 as adjuvant therapy for triple receptor-negative breast cancer with > 1 cm residual invasive cancer or positive lymph nodes (>pN1mic) after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-02-04.