Abstract PS12-16: Pilot study of carboplatin, nab-paclitaxel and pembrolizumab for metastatic triple-negative breast cancer
Authors: Baar Joseph , Abraham Jame , Budd G. Thomas , Silverman Paula , Montero Alberto , Moore Halle , Fu Pingfu , Varadan Vinay , Ladaika Kara , Hricik Lauren 
Published: February 2021

Abstract
Background. Given the significant clinical activity of the anti-PD1 inhibitor pembrolizumab as either a single agent or in combination with cytotoxic chemotherapy in the treatment of patients with metastatic triple-negative breast cancer (mTNBC), as well as the favorable cytotoxic and immunomodulatory properties of carboplatin and nab-paclitaxel, we identified a strong rationale to treat patients with mTNBC with the combination of carboplatin (C), nab-paclitaxel (N) and pembrolizumab (P) (CNP).
Material and Methods. We undertook a prospective, single-arm pilot study of 30 patients with mTNBC treated at two institutions. Inclusion criteria included: radiographically measurable mTNBC, ECOG performance status of 0-1, &lt;2 prior therapies for mTNBC, and willingness to undergo a primary pre-treatment biopsy of a metastatic focus for research purposes. A second post-treatment research biopsy was encouraged but not mandated. Eligible patients received 3 cycles of CNP, with each cycle initially consisting of C (AUC 6 on days 1 of a 21-day cycle), N (100 mg/m2 IV on days 1, 8 and 15 of a 21-day cycle), and P (200 mg IV on day 15 of each cycle). Because of significant bone marrow toxicity, C was subsequently reduced to AUC 4.2 and N was reduced to 75 mg/m2. After completing 3 cycles of CNP, patients with either responding or stable disease by RECIST 1.1 criteria were eligible for additional cycles of CNP. The primary objective of this study was to determine overall response rate (ORR) in patients treated with CNP. The true response rate of therapy was estimated based on the number of responses using a binomial distribution and its confidence intervals were estimated using Wilson's method. Secondary objectives included: determine progression-free survival (PFS) and safety/tolerability of CNP. The Kaplan-Meier method was used to estimate PFS and OS. The probability of PFS at 6, 12, and 18 months were 51.8%, 24.7%, and 6.2%, respectively. The median PFS was 6.1 (95% CI: 5.1, 11) months. The probability of OS at 6, 12, and 18 months were 79%, 47%, and 5.9%, respectively. The median OS was 11.5 (95% CI: 8, 14.1) months. Correlative biopsy analyses will be undertaken to identify pathologic and genomic correlates of response to CNP. Factors including pathologic and genomic correlates that predict survival outcomes will be identified by Cox model or extensions of the Cox model.Results. Twenty nine patients have completed treatment and 1 remains on single-agent P. ORR was 53% (2 CRs and 14 PRs). Four patients had SD. The most common toxicity was infection (10 patients, grade 3) .The most common immune-related adverse events were pneumonitis (1 patient, grade 3) and hepatitis (1 patient, grade 3). There was only 1 grade 4 toxicity (increased creatinine).
Conclusions. CNP demonstrated significant activity in patients with mTNBC. Studies are underway to identify pathologic and genomic correlates of clinical response to CNP.
Citation Format: Joseph Baar, Jame Abraham, G. Thomas Budd, Paula Silverman, Alberto Montero, Halle Moore, Pingfu Fu, Vinay Varadan, Kara Ladaika, Lauren Hricik. Pilot study of carboplatin, nab-paclitaxel and pembrolizumab for metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-16.