Neoadjuvant Pembrolizumab Plus Carboplatin and Docetaxel Improved Response, Survival Rates Among Patients With Triple-Negative Breast Cancer

Clinical and Biomarker Results From the Phase 2 NeoPACT Trial 

According to clinical and biomarker results from the phase 2 NeoPACT trial, neoadjuvant pembrolizumab plus carboplatin and docetaxel improved pathological complete response (pCR) and 3-year event-free survival (EFS) rates among patients with triple-negative breast cancer. 

While it is known that the “addition of pembrolizumab to anthracycline-based chemotherapy improves [pCR] and [EFS] in triple-negative breast cancer,” as Priyanka Sharma, MD, University of Kansas Medical Center, Westwood, and coauthors stated, “the efficacy of anthracycline-free chemoimmunotherapy in [triple-negative breast cancer] has not been assessed.” 

In this open-label study, 115 patients with stage 1 to 3 triple-negative breast cancer were treated with 200 mg of pembrolizumab plus carboplatin and docetaxel every 21 days for 6 cycles. Additionally, RNA isolated from pretreatment tumor tissue underwent next-generation sequencing. Specimens were classified as node-positive or node-negative for the 44-gene DNA damage immune response (DDIR) signature and for the 27-gene tumor immune microenvironment (TIM) signature based on predefined cutoffs. The primary end point was pCR. Secondary end points included residual cancer burden, EFS, toxicity, and immune biomarkers.

At analysis, 39% of all patients had node-positive disease. The pCR was 58% and the residual cancer burden 0 + 1 rate was 69%. Grade ≥ 3 immune-mediated adverse events occurred in 3.5% of patients. Estimated 3-year EFS was 86% among all patients, 98% in the pCR group, and 68% in the non-pCR group. In multivariate analyses, sTILs, PD-L1, DDIR, and TIM were each predictive of pCR.

Dr Sharma et al concluded, “These results provide data on an alternative anthracycline-free chemoimmunotherapy regimen for patients who are not eligible for anthracycline-based regimens and support further evaluation of this regimen as a chemotherapy de-escalation strategy in randomized studies for [triple-negative breast cancer].”

Source: 

Sharma P, Stecklein SR, Yoder R, et al. Clinical and biomarker findings of neoadjuvant pembrolizumab and carboplatin plus docetaxel in triple-negative breast cancer. JAMA Oncol. Published online November 22, 2023. doi:10.1001/jamaoncol.2023.5033