Second- or third-line treatment with pembrolizumab did not improve overall survival (OS), when compared with single-agent chemotherapy, in patients with metastatic triple-negative breast cancer (TNBC), according to results published in The Lancet Oncology.
In the phase 3 KEYNOTE-119 trial (ClinicalTrials.gov Identifier: NCT02555657), 622 patients were randomly assigned to receive pembrolizumab (n=312) or investigator’s choice of chemotherapy (n=310). The chemotherapy options were capecitabine, eribulin, gemcitabine, or vinorelbine.
Patients were stratified by PD-L1 status (combined positive score [CPS] ≥ 1 vs CPS < 1) and history of previous treatment (neoadjuvant/adjuvant treatment vs de novo metastatic disease).
The median follow-up was 31.4 months for the pembrolizumab arm and 31.5 months for the chemotherapy arm.
There was no significant difference in OS between the treatment arms. The median OS was 9.9 months in the pembrolizumab arm and 10.8 months in the chemotherapy arm (hazard ratio [HR], 0.97; 95% CI, 0.82-1.15).
However, results suggested that pembrolizumab efficacy increases with increasing PD-L1 expression.
Among patients with a PD-L1 CPS of 1 or more, the median OS was 10.7 months in the pembrolizumab arm and 10.2 months in the chemotherapy arm (HR, 0.86; 95% CI, 0.69-1.06; log-rank P =.073).
Among patients with a PD-L1 CPS of 10 or more, the median OS was 12.7 months in the pembrolizumab arm and 11.6 months in the chemotherapy arm (HR, 0.78; 95% CI, 0.57-1.06; log-rank P =.057).
In an exploratory analysis of patients with a PD-L1 CPS of 20 or more, the median OS was 14.9 months in the pembrolizumab arm and 12.5 months in the chemotherapy arm (HR, 0.58; 95% CI, 0.38-0.88).
The rate of grade 3-4 treatment-related adverse events was 14% in the pembrolizumab arm and 36% in the chemotherapy arm. The most common of these events were anemia, decreased white blood cell count, decreased neutrophil count, and neutropenia.
The rate of serious adverse events was 20% in both arms. There were 3 fatal adverse events — 1 due to circulatory collapse in the pembrolizumab arm, 1 due to pancytopenia and sepsis in the chemotherapy arm, and 1 hemothorax in the chemotherapy arm.
“Although results from exploratory analyses must be considered hypothesis-generating, it appears that the highest benefit with pembrolizumab was observed in an unplanned subset of participants with strongly positive PD-L1-expressing tumors (CPS ≥20), comprising approximately 18% of the overall study population,” the study authors wrote.
“These findings might inform future research of pembrolizumab monotherapy for selected subpopulations of patients, specifically those with PD-L1-enriched tumors, and
inform a combinatorial approach for the treatment of patients with metastatic triple-negative breast cancer.”
Disclosures: This research was supported by Merck Sharp & Dohme. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Winer EP, Lipatov O, Im S-A, et al; KEYNOTE-119 investigators. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(4):499-511. doi:10.1016/S1470-2045(20)30754-3