Final results from the pivotal phase 3 KEYNOTE-355 trial showed that the addition of pembrolizumab (Keytruda) to chemotherapy resulted in a statistically significant and clinically meaningful improvement in overall survival (OS) compared with chemotherapy alone in patients with metastatic triple-negative breast cancer (TNBC) whose tumors expressed PD-L1 with a combined positive score (CPS) ≥10. These findings were presented at the 2021 San Antonio Breast Cancer Symposium by Javier Cortés, MD, PhD, Head, Breast Cancer Unit, IOB Institute of Oncology, Quiron Group, Madrid and Barcelona, Spain, and Clinical Investigator, Breast Cancer Research Program, Vall d’Hebron Institute of Oncology, Barcelona.
“The study met its dual primary end point, showing a statistically significant and clinically meaningful improvement in progression-free survival [PFS] and OS for pembrolizumab plus chemotherapy versus chemotherapy alone for the first-line treatment of PD-L1 CPS >10 metastatic TNBC. No new safety concerns emerged during the trial,” Dr Cortés stated. “CPS >10 is a reasonable cut-off to define the population of women with metastatic TNBC expected to derive treatment benefit from pembrolizumab plus chemotherapy.”
Pembrolizumab is currently approved by the FDA in combination with chemotherapy for the treatment of patients with locally recurrent, unresectable, or metastatic TNBC whose tumors express PD-L1 (CPS >10) as determined by an FDA-approved test.
“In my opinion, the results of KEYNOTE-355 lend further support for pembrolizumab plus chemotherapy as a standard-of-care treatment regimen for this group of patients,” Dr Cortés stated.
These results for OS follow those of a previous interim analysis presented at the 2021 European Society for Medical Oncology Congress, showing that pembrolizumab in combination with chemotherapy significantly improved PFS compared with chemotherapy alone in these patients.
In the phase 3 KEYNOTE-355 trial, investigators randomized 847 patients with previously untreated, locally recurrent inoperable or metastatic breast cancer whose tumors expressed PD-L1 to receive pembrolizumab plus chemotherapy (N = 566) or placebo plus chemotherapy (N = 281). Chemotherapy options included nab-paclitaxel (Abraxane), paclitaxel, and gemcitabine/carboplatin (Gemzar).
At baseline, approximately 75% had tumors expressing PD-L1 with CPS ≥1 for the pembrolizumab and placebo arms, and approximately 38% had tumors expressing PD-L1 with CPS ≥10 in both arms. Patients were stratified according to type of chemotherapy (taxane or gemcitabine/carboplatin) and PD-L1 status (CPS >1 or <1).
The final analysis presented by Dr Cortés compared outcomes in subgroups according to additional CPS cutoffs (CPS 1-9, CPS 10-19, and CPS >20) versus the primary analysis. Baseline characteristics in these subgroups were similar to those in the overall trial. PD-L1 expression according to CPS was well-balanced between the 2 treatment arms: CPS 10-19 was seen in 14.1% of the pembrolizumab plus chemotherapy arm versus 13.9% in the placebo plus chemotherapy arm; CPS 10-20 was observed in approximately 24% of both arms.
In the primary analysis of OS, a statistically significant difference favoring pembrolizumab plus chemotherapy was observed in patients with CPS >10, who had a 37% improvement in OS (P = .0061). Among patients with CPS >1, a 12% nonsignificant trend in improved OS was observed, favoring the pembrolizumab plus chemotherapy regimen.
“OS was similar in the pembrolizumab and placebo subgroups with CPS <1 and CPS 1-9. The benefit of pembrolizumab and chemotherapy was pretty much the same for CPS 10-19 and CPS >20,” Dr Cortés said.
“For the final analysis of PFS, a trend was observed for improvement with PD-L1 enrichment CPS >10,” he said. “The general trend for PFS was consistent with that observed for OS.”
The most common treatment-related adverse events (AEs) were anemia, neutropenia, nausea, alopecia, and fatigue, and rates were comparable between the 2 arms of the study.
The rate of treatment-related AEs of any grade was similar in both arms of the study: 96.3% of the pembrolizumab arm and 95% of the placebo arm. Grades 3 to 5 treatment-related AEs were reported in 68.1% and 66.9% of patients, respectively. Grades 3 to 5 immune-mediated AEs occurred in 5.3% of patients treated with the pembrolizumab-based combination and 0% of those treated with chemotherapy alone.