Overall response rates of 13-19% have been reported with checkpoint inhibitor monotherapy in chemotherapy-resistant, PD-L1-positive mTNBC. RT is frequently used to enhance local control in mTNBC and has been reported to induce distant (abscopal) tumor responses when combined with immunotherapy. In this study we evaluate the safety and efficacy of RT combined with the anti-PD-1 inhibitor, pembro, in a single-arm, two-stage, phase II study in mTNBC (NCT02730130).
Eligible women had biopsy-proven mTNBC, ECOG performance status 0-2, and ≥2 measurable sites of metastatic disease with at least 1 site requiring RT. A total RT dose of 3000 cGy was delivered in 5 daily fractions. IV pembro was given at 200mg within 3 days of first RT fraction then every 3 weeks until disease progression. The primary endpoint was overall response rate at week 13 in the non-irradiated lesions by RECIST v1.1. Secondary endpoints included safety and overall survival. Tumor biopsies were obtained at baseline and at week 7. PD-L1 expression was not required for study entry.
As of May 1, 2017, the study has completed enrollment (N = 17) with 4 women on treatment pending 13-week evaluation. Median age was 52y (range 37-73y). Median number of prior therapies received for metastatic disease was 3 (range 0 to 8). Of the 7 women not evaluable at 13 weeks: 5 died secondary to disease-related complications (at weeks 2, 6, 7, 8, and 9) and 2 came off study due to disease progression prior to week 13. Of the 6 women evaluable at week 13, 2 (33%) had a partial response (PR), 1 (17%) had stable disease (SD) and 3 (50%) had disease progression. The 2 PRs represented 76% and 75% decreases in tumor burden by RECIST v1.1 durable for 21 and 31 weeks, respectively. SD response was durable for 30 weeks. Common toxicities were mild and included fatigue, myalgia and nausea.
The combination of pembro and RT was well-tolerated. This is a poor prognosis population with 5/13 (38%) evaluable patients dying within 12 weeks of study entry. However, durable responses were observed outside of the RT field in 2/6 (33%) patients who were unselected for PD-L1 expression and evaluable at 13 weeks. Safety and toxicity data for all study patients will be presented.
Clinical trial identification
Legal entity responsible for the study
Memorial Sloan Kettering Cancer Center
H.L. McArthur: Advisory boards for Celgene, Merck, OBI Pharma, Spectrum, Syndax, Roche, Peregrine, Calithera, Eli Lilly, and TapImmune. Research supported by Bristol-Myers Squibb; Eli Lilly; MedImmune, LLC/AstraZeneca; and Merck. C.A. Barker: In the past year has received research funding from Elekta, Merck, and Amgen; honoraria from Driver Group, a biotechnology company; and served as a Pfizer advisory board consultant. A. Gucalp: Research funding from Pfizer and Innocrin related to other work in triple negative breast cancer. A. Ho: Research funding by Merck. All other authors have declared no conflicts of interest.