SABCS 2020: Pembrolizumab Plus Chemo Continues to Shine in New KEYNOTE-355 Analysis

By Kate O’Rourke

Pembrolizumab plus chemotherapy improved the progression-free survival, overall response rate, durable complete remission, and duration of response for patients with locally recurrent, unresectable or metastatic triple negative breast cancer (TNBC) with tumors expressing PD-L1 and a combined positive score (CPS) of 10 or more, according to new findings from the KEYNOTE-355 trial.

The additional endpoint results, which were reported at the 2020 San Antonio Breast Cancer Symposium, follow a previously reported progression-free survival (PFS) benefit for the pembrolizumab and chemotherapy combination during an interim analysis. In November 2020, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab, in combination with chemotherapy, based on the earlier results.

“A trend towards improved outcomes with PD-L1 enrichment was observed in patients treated with pembrolizumab and chemotherapy,” said Hope Rugo, MD, professor of medicine in the Division of Hematology and Oncology at the University of California San Francisco Comprehensive Cancer Center, who presented the study.

In the randomized KEYNOTE-355 trial, 847 patients with previously untreated metastatic TNBC were randomized 2-to-1 to receive the investigator’s choice of chemotherapy, including nab-paclitaxel, paclitaxel or gemcitabine/carboplatin, with pembrolizumab or placebo (Abstract GS3-01). Either pembrolizumab or placebo was administered in a double-blind fashion for up to 35 infusions, and treatment was continued until disease progression, unacceptable toxicity, withdrawal of consent, or physician-patient decision. Crossover was not allowed. The median follow up was approximately 26 months in both study cohorts.

Among patients with a PD-L1 CPS of at least 10, the median PFS was 9.7 months in the pembrolizumab arm and 5.6 months in the placebo arm. In total, 61.8% of patients receiving pembrolizumab experienced disease progression or death, compared with 76.7% in the placebo group (Hazard Ratio [HR] 0.65; 95% CI, 0.49-0.86; P=0.0012). The survival difference reached statistical significance.

However, the PFS difference between pembrolizumab and placebo did not reach statistical significance, based on pre-specified criteria, among patients with a PD-L1 CPS of at least 1. In that subgroup, the median PFS was 7.6 months in the pembrolizumab group and 5.6 months in the placebo group. In total, 67.8% of patients in the pembrolizumab group experienced disease progression or death, compared with 76.8% in the placebo group (HR 0.74; 95% CI, 0.61-0.90; P=0.0014).

Statistical significance was not tested in the intent-to-treat population, which had a median PFS of 7.5 months in the pembrolizumab group and 5.6 months in the placebo group. In total, 69.1% of patients in the pembrolizumab group experienced disease progression or death, compared with 75% in the placebo group (HR 0.82; 95% CI, 0.69-0.97).

The hazard ratio for PFS favored pembrolizumab and chemotherapy regardless of the choice of chemotherapy partner or the CPS population, Dr. Rugo explained.

Investigators also observed an overall response and disease control response benefit for pembrolizumab versus placebo across PD-L1 CPS groups and in the intent-to-treat population. However, in the pembrolizumab group, a PD-L1 CPS score of 10 or more resulted in a higher overall response rate, compared with a PD-L1 CPS score of at least 1 and the PD-L1 unselected intent-to-treat population.

In each population, the median duration of response was longer with pembrolizumab versus placebo. A greater proportion of patients in the pembrolizumab group had a duration of response of 6 months or longer and 12 months or longer, versus the chemotherapy group. Additionally, a longer duration of response was observed with increasing PD-L1 enrichment.

“These data further support a role for the addition of pembrolizumab to standard chemotherapy for the first-line treatment of metastatic TNBC,” Dr. Rugo said.


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