Phase II study of pembrolizumab and capecitabine for triple negative and hormone receptor-positive, HER2−negative endocrine-refractory metastatic breast cancer. Issue 1 (13th February 2020)

• Record Type: Journal Article
• Authors: Shah, Ami N; Flaum, Lisa; Helenowski, Irene; Santa-Maria, Cesar A; Jain, Sarika; Rademaker, Alfred; Nelson, Valerie; Tsarwhas, Dean; Cristofanilli, Massimo; Gradishar, William
• Is Part Of: Journal for immunotherapy of cancer. Volume 8:Issue 1(2020)
• Publication Date: 2020-02-13
• Subjects: immunology -- oncology -- breast neoplasms -- programmed cell death 1 receptor; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2019-000173
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : Background: Response rates to single agent immune checkpoint blockade in unselected pretreated HER2−negative metastatic breast cancer (MBC) are low. However, they may be augmented when combined with chemotherapy. Methods: We conducted a single-arm, phase II study of patients with triple negative (TN) or hormone receptor-positive endocrine-refractory (HR+) MBC who were candidates for capecitabine. Patients were treated with pembrolizumab 200 mg intravenously day 1 and capecitabine 1000 mg/m 2 by mouth twice daily on days 1–14 of a 21-day cycle. The primary end point was median progression-free survival (mPFS) compared with historic controls and secondary end points were overall response rate (ORR), safety and tolerability. The study had 80% power to detect a 2-month improvement in mPFS with the addition of pembrolizumab over historic controls treated with capecitabine alone. Results: Thirty patients, 16 TN and 14 HR+ MBC, were enrolled from 2017 to 2018. Patients had a median age of 51 years and received a median of 1 (range 0–6) prior lines of therapy for MBC. Of 29 evaluable patients, the mPFS was 4.0 (95% CI 2.0 to 6.4) months and was not significantly longer than historic controls of 3 months. The median overall survival was 15.4 (95% CI 8.2 to 20.3) months. The ORR was 14% (n=4), stable disease (SD) was 41% (n=12) and clinical benefit rate (CBR=partial response+SD>6 months) was 28% (n=8). The ORR and CBR were not significantly different between disease subtypes (ORR 13% and 14%, CBR 25% and 29% for TN and HR+, respectively). The 1-year PFS rate was 20.7% and three patients have ongoing responses. The most common adverse events were low grade and consistent with those seen in MBC patients receiving capecitabine, including hand-foot syndrome, gastrointestinal symptoms, fatigue and cytopenias. Toxicities at least possibly from pembrolizumab included grade 3 or 4 liver test abnormalities (7%), rash (7%) and diarrhea (3%), as well as grade 5 hepatic failure in a patient with liver metastases. Conclusions: Compared with historical controls, pembrolizumab with capecitabine did not improve PFS in this biomarker unselected, pretreated cohort. However, some patients had prolonged disease control. Trial registration number: NCT03044730 .