First-Line Pembrolizumab plus Chemotherapy Extend Progression-Free Survival in Patients with Metastatic Triple-Negative Breast Cancer

April 2021, Vol 12, No 2

Pembrolizumab (Keytruda) plus chemotherapy improved progression-free survival (PFS) compared with chemotherapy alone as first-line treatment of metastatic triple-negative breast cancer (TNBC), according to the results of KEYNOTE-355. Improvement in PFS with the addition of pembrolizumab to chemotherapy was more robust in patients with TNBC and PD-L1 expression. These results from KEYNOTE-355 were presented at the 2020 San Antonio Breast Cancer Symposium (SABCS) and add to a growing body of evidence supporting the first-line use of pembrolizumab plus chemotherapy combinations for TNBC.

“Pembrolizumab plus chemotherapy achieved a statistically significant and clinically meaningful improvement in progression-free survival versus chemotherapy alone for first-line treatment of PD-L1–positive metastatic TNBC. A trend toward improved progression-free survival was observed with PD-L1 enrichment regardless of chemotherapy partner, regardless of which chemotherapy was used,” said lead investigator Hope S. Rugo, MD, FASCO, Director, Breast Oncology and Clinical Trials Education, University of California San Francisco Helen Diller Family Comprehensive Cancer Center.

Pembrolizumab plus chemotherapy was previously approved by the FDA for neoadjuvant treatment of patients with TNBC. Based on the results from KEYNOTE-355, the FDA granted the combination of pembrolizumab and chemotherapy accelerated approval for the treatment of patients with locally recurrent unresectable or metastatic TNBC with PD-L1 expression (ie, combined positive score [CPS] ≥10), extending the approval to the advanced cancer setting.

Atezolizumab (Tecentriq), another checkpoint inhibitor, is also approved for the treatment of patients with TNBC and PD-L1 expression.


The randomized, placebo-controlled phase 3 KEYNOTE-355 clinical trial was conducted at 209 sites in 24 countries around the world and enrolled 847 treatment-naïve women with locally recurrent unresectable or metastatic TNBC who completed curative treatment more than 6 months before first disease recurrence. Patients with active central nervous system disease were excluded.

Participants were randomized in a 2:1 ratio to pembrolizumab (35 infusions in every 3-week cycles) plus investigator’s choice of chemotherapy (taxane- or anthracycline-based) or to chemotherapy alone. Treatment was continued until progressive disease or cessation of study therapy. Crossover was not allowed. The median follow-up was approximately 26 months.

The primary end points were PFS and overall survival. The secondary end points included overall response rate, disease control rate, and duration of response. An exploratory end point was the consistency of treatment effect in all patients (intent-to-treat [ITT]) and in patients with tumors expressing PD-L1 CPS ≥10 and CPS ≥1.

The baseline disease and demographic characteristics were well-balanced between the 2 arms. Approximately 75% had PD-L1 expression of CPS ≥1, and 38% had CPS ≥10.

For the primary analysis of PFS, which was presented at ASCO 2020, pembrolizumab plus chemotherapy significantly improved PFS in patients with PD-L1 CPS ≥10 versus chemotherapy alone (P = .0012).

New Results

At the SABCS 2020 meeting, Dr Rugo presented PFS results by chemotherapy partner and secondary end points. In patients with PD-L1 of CPS ≥10, 76.7% of the patients who received pembrolizumab plus chemotherapy versus 61.8% of those who received chemotherapy alone were free of disease progression or death at 6 months. The median PFS was 9.7 months and 5.6 months, respectively, for a significant 35% reduction in risk favoring the pembrolizumab arm (P = .0012).

“The separation of progression-free survival curves began at 4 months,” Dr Rugo noted.

Among patients with PD-L1 of CPS ≥1, at 6 months, 56.4% of those in the combination arm and 47.8% of the chemotherapy-alone arm were free of disease progression or death. The median PFS was 7.6 months and 5.6 months, respectively, for a 26% reduction in risk favoring the pembrolizumab-containing arm (P = .0014).

A 6-month analysis of the ITT population showed that 55.4% and 47%, respectively, had disease progression or death. The median PFS was 7.5 and 5.6 months, respectively, for an 18% reduction in risk with pembrolizumab.

Subgroup analyses of PFS according to the type of chemotherapy used also favored the combination of pembrolizumab plus chemotherapy versus chemotherapy alone in PD-L1 CPS ≥10, CPS ≥1, and ITT.

“Regardless of chemotherapy partner, overall response rates were higher with pembrolizumab plus chemotherapy,” Dr Rugo noted.

Disease control rates and duration of response rates were also superior with pembrolizumab plus chemotherapy versus chemotherapy alone, and these rates improved in a linear fashion with the increase in PD-L1 expression. The overall survival results will be reported in the future.

Related Articles