Title

A phase Ib trial of pembrolizumab plus paclitaxel or flat-dose capecitabine in 1st/2nd line metastatic triple-negative breast cancer.

Authors

David B Page, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Joanna Pucilowska, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Brie Chun, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Isaac Kim, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Katherine Sanchez, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.
Nicole Moxon, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Staci Mellinger, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Yaping Wu, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Yoshinobu Koguchi, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Valerie Conrad, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
William L Redmond, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Maritza Martel, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Zhaoyu Sun, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Mary B Campbell, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Alison Conlin, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Anupama Acheson, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.
Reva Basho
Philomena McAndrew
Mary El-Masry
Dorothy Park
Laura Bennetts, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Robert S Seitz
Tyler J Nielsen
Kimberly McGregor
Venkatesh Rajamanickam, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Brady Bernard, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Walter J Urba, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.Follow
Heather L McArthur

Document Type

Article

Publication Date

6-21-2023

Publication Title

NPJ Breast Cancer

Keywords

oregon; chiles

Abstract

Chemoimmunotherapy with anti-programmed cell death 1/ligand 1 and cytotoxic chemotherapy is a promising therapeutic modality for women with triple-negative breast cancer, but questions remain regarding optimal chemotherapy backbone and biomarkers for patient selection. We report final outcomes from a phase Ib trial evaluating pembrolizumab (200 mg IV every 3 weeks) with either weekly paclitaxel (80 mg/m2 weekly) or flat-dose capecitabine (2000 mg orally twice daily for 7 days of every 14-day cycle) in the 1st/2nd line setting. The primary endpoint is safety (receipt of 2 cycles without grade III/IV toxicities requiring discontinuation or ≥21-day delays). The secondary endpoint is efficacy (week 12 objective response). Exploratory aims are to characterize immunologic effects of treatment over time, and to evaluate novel biomarkers. The trial demonstrates that both regimens meet the pre-specified safety endpoint (paclitaxel: 87%; capecitabine: 100%). Objective response rate is 29% for pembrolizumab/paclitaxel (n = 4/13, 95% CI: 10-61%) and 43% for pembrolizumab/capecitabine (n = 6/14, 95% CI: 18-71%). Partial responses are observed in two subjects with chemo-refractory metaplastic carcinoma (both in capecitabine arm). Both regimens are associated with significant peripheral leukocyte contraction over time. Response is associated with clinical PD-L1 score, non-receipt of prior chemotherapy, and the H&E stromal tumor-infiltrating lymphocyte score, but also by a novel 27 gene IO score and spatial biomarkers (lymphocyte spatial skewness). In conclusion, pembrolizumab with paclitaxel or capecitabine is safe and clinically active. Both regimens are lymphodepleting, highlighting the competing immunostimulatory versus lymphotoxic effects of cytotoxic chemotherapy. Further exploration of the IO score and spatial TIL biomarkers is warranted. The clinical trial registration is NCT02734290.

Clinical Institute

Cancer

Clinical Institute

Women & Children

Department

Oncology

Share

COinS