Pembro + chemo prolongs OS in TNBC patients with high PD-L1 expression

Adding pembrolizumab to chemotherapy in the first-line setting significantly prolongs overall survival (OS) in patients with triple-negative breast cancer (TNBC) whose tumours expressed programmed death-ligand 1 (PD-L1) with a CPS* of ≥10, compared with chemotherapy alone, according to the KEYNOTE-355** trial.

This phase III, international, double-blind trial involved 847 patients with previously untreated locally recurrent inoperable or metastatic TNBC, of whom 75.1 and 38.1 percent had a CPS of ≥10 and ≥1, respectively. Participants were randomized in a 2:1 ratio to receive either intravenous pembrolizumab 200 mg every 3 weeks for up to a maximum of 35 administrations (n=566) or placebo (n=281) in addition to the investigator’s choice of chemotherapy***. [N Engl J Med 2022;387:217-226]

At a median follow-up of 44.1 months, patients with PD-L1 CPS of ≥10 who received pembro + chemo had a significantly longer median OS than those who received placebo + chemo (23.0 vs 16.1 months; hazard ratio [HR], 0.73; two-sided p=0.0185).

Among those with PD-L1 CPS of ≥1, the median OS was not significantly different between the pembro + chemo and placebo + chemo arms (17.6 vs 16.0 months; HR, 0.86; two-sided p=0.1125).

Treatment-related adverse events (AEs) occurred at a similar rate between the pembro + chemo and placebo + chemo arms (96.3 percent vs 95.0 percent). Anaemia, neutropenia, and nausea were the most common grade ≥3 AEs reported in both treatment arms.

The safety profile of pembro + chemo regimen was consistent with that observed in a previous study, with no new safety signals identified, noted the researchers.

In an exploratory analysis of patients with additional PD-L1 CPS cut-offs, both treatment arms showed similar OS among patients whose tumours expressed PD-L1 with a CPS of 10–19 (HR, 0.71) and ≥20 (HR, 0.72). “This finding provides further support that a CPS of ≥10 is an appropriate criterion to define the population of patients with advanced TNBC who would be expected to derive benefit from pembro + chemo,” the researchers noted.

“[Moreover,] the treatment effect of pembrolizumab on OS increased with higher PD-L1 expression, with similar treatment effects observed among patients whose tumours expressed PD-L1 with a CPS of ≥10 and ≥20,” said the researchers.

“The results of this protocol-specified final analysis showed that [first-line treatment with] pembro + chemo resulted in significantly longer OS than chemo alone among patients with advanced TNBC whose tumours expressed PD-L1 with a CPS of ≥10,” the researchers concluded.

*CPS: Combined positive score

**KEYNOTE-355: Study of pembrolizumab (MK-3475) plus chemotherapy vs placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer

***nanoparticle albumin-bound (nab)-paclitaxel 100 mg/m² and paclitaxel 90 mg/m² on days 1, 8, and 15 of every 28-day cycle; or gemcitabine 1,000 mg/m² plus carboplatin on days 1 and 8 of every 21-day cycle