Abstract P2-14-03: A pilot study of paclitaxel plus pembrolizumab in patients with metastatic HER2-negative breast cancer (PePPy)
Authors: Tan Antoinette R. , Chai S. Jean , Robinson Myra M. , Hellner Lane B. , Gavini Nagajyothi , Sulai Nanna , Turner J. David , Atlas Jennifer , Graham David L. , Induru Raghava R. , Kadakia Kunal C. , Vallabhaneni Geetha D. , Heeke Arielle L. , Foureau David M. , Fisher Julie G. 
Published: March 2022

Abstract
Background: Studies of immune checkpoint inhibitors combined with chemotherapy show activity in metastatic breast cancer (MBC). There is no data regarding sequencing of pembrolizumab (pem) in relation to chemotherapy in MBC patients (pts). We investigated the safety of a phased schedule vs concurrent schedule of paclitaxel (pac) and pembrolizumab (pem). Methods: Eligible pts had HR+HER2-negative or triple-negative (TN) MBC, ≥2 lines of hormone therapies and 0-3 prior lines of chemotherapy for MBC. Pts were randomized 1:1 to 2 cycles of pac 80 mg/m2 IV on D1 and D8 followed by pac and pem 200 mg/m2 IV on D1 of a 21-day cycle (Arm A; phased schedule) or pac and pem given together starting D1 of a 21-day cycle (Arm B; concurrent) and continuing until progression or toxicity. Primary objective was to continuously monitor overall grade 3 or 4 treatment-related adverse event (TRAE) rate for each arm and compare to relevant historical controls with Bayesian stopping rules. If the grade 3 or 4 TRAE rate convincingly exceeded 0.35 on either arm, enrollment to that arm would be halted. Secondary objectives were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Exploratory analyses assessed PD-L1 and tumor infiltrating lymphocytes (TILs) in the tumor and blood markers immunotyping. Results: Forty female pts were randomized (21 in Arm A and 19 in Arm B). Median age was 40 (range 28-76). Twenty pts were HR+HER2-negative; 20 pts had TNBC; 7 pts had de novo MBC. Median prior lines of chemotherapy was 1 (range 0 - 3); median no. of cycles was 7 (1-27); 7 pts in Arm A did not initiate pembrolizumab due to disease progression. The criteria for stopping enrollment based on Bayesian stopping rules were not met for either arm; 24% of subjects (5 of 21) on Arm A and 32% (6 of 19) on Arm B experienced stopping rule events. At the data cut-off of 2/16/21, with median follow-up of 10.1 months, overall ORR was 30% with 12 partial responses, and ORR in HR+HER2-negative and TNBC were 30% and 30%, respectively. Grade 3-4 TRAE rates were 24% in Arm A and 32% in Arm B. The most common grade 3-4 TRAES were peripheral sensory neuropathy (2 pts [10%] in Arm A; 3 pts [16%] in Arm B), decreased neutrophil count (1 pt [5%] in each Arm), and anemia (1 pt [5%] in each Arm). In the overall group, immune-related adverse events (irAEs) occurred in 28% of pts; 5% of these events were ≥ grade 3 in Arm A (gr 3 AST/ALT increased in 1 pt) and 5% in Arm B (gr 3 lipase increased in 1 pt). The most common irAE was hypothyroidism (6 pts, 15%). Tumor PD-L1 assay and TILs were performed in 39 pts and blood immunotyping on all pts. Seven pts (18%) had PD-L1 positive tumors (PDL-1 H-score ≥ 5, centrally tested) and 19 (48.7%) had significant immune infiltration (TILs score 2-3). Biomarker analysis is currently in progress. Updated data, including ORR, PFS and OS by arm, is expected to be presented. Conclusions: Both the phased and concurrent schedules of pac and pem were found to be safe and feasible. The combination’s safety profile was consistent with the known individual agent’s safety profile. Clinical activity was demonstrated in both metastatic HR+HER2-negative and TNBC pts. Clinical trial information: NCT03018080.
Citation Format: Antoinette R. Tan, S. Jean Chai, Myra M. Robinson, Lane B. Hellner, Nagajyothi Gavini, Nanna Sulai, J. David Turner, Jennifer Atlas, David L. Graham, Raghava R. Induru, Kunal C. Kadakia, Geetha D. Vallabhaneni, Arielle L. Heeke, David M. Foureau, Julie G. Fisher. A pilot study of paclitaxel plus pembrolizumab in patients with metastatic HER2-negative breast cancer (PePPy) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-14-03.