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Pembrolizumab (Keytruda) plus chemotherapy as first-line treatment significantly improved overall survival (OS) for patients with metastatic triple-negative breast cancer (TNBC) whose tumors express a certain level of PD-L1, according to results from the KEYNOTE-355 trial.

In patients with a PD-L1 combined positive score (CPS) ≥10, chemotherapy plus pembrolizumab increased median survival by almost 7 months versus chemotherapy plus placebo, and reduced the risk of death by 27% at a median follow-up of 44 months (HR 0.73, 95% 0.55-0.95), reported Hope S. Rugo, MD, of the University of California Helen Diller Family Comprehensive Cancer Center in San Francisco.

Rugo said updated progression-free survival (PFS) results in the CPS ≥10 group were consistent with those previously reported, with 65.5% in the pembrolizumab group and 78.6% in the placebo group experiencing a PFS event at data cutoff (HR 0.66, 95% CI 0.50-0.88). PFS results led to accelerated approval of the combination last year, which was recently converted to full FDA approval.

"These results support pembrolizumab/chemotherapy as a new standard-of-care treatment regimen for patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 with CPS ≥10," she said in a presentation at the European Society for Medical Oncology (ESMO) virtual meeting.

There was no added benefit with pembrolizumab when applying a cutoff of CPS ≥1, however.

Still, ESMO discussant Gonzalo Gomez-Abuin, MD, of Hospital Alemán in Buenos Aires, agreed with Rugo, and called the regimen a "transformative treatment."

In KEYNOTE-355, 847 patients were randomized 2:1 to receive either pembrolizumab plus chemotherapy, or placebo plus chemotherapy. Median follow-up was approximately 44 months in both groups.

Baseline characteristics were similar between the two groups, with 75.1% of patients having a CPS ≥1 PD-L1 expression level, and 38.9% having a CPS ≥10. In addition, 45.1% received taxanes as chemotherapy during the study, while 54.9% received gemcitabine/carboplatin.

Median OS was 23 months in the pembrolizumab group for the CPS ≥10 group versus 16.1 months in the placebo group, with an estimated OS at 18 months of 58.3% and 44.7% in the two groups, respectively.

For the CPS ≥1 group, the median OS was 17.6 months in the pembrolizumab group and 16.0 months in the placebo group.

"There was a trend towards improved efficacy with PD-L1 enrichment that seemed to plateau at a CPS cutoff of 10 in patients treated with pembrolizumab/chemotherapy," Rugo reported, while in the CPS ≥10 group, the benefit of the pembrolizumab regimen on OS was generally consistent across most predefined subgroups.

However, she added that "Although it appears the benefit of pembrolizumab/chemotherapy was not observed in patients with a disease-free interval of less than 12 months, results should be interpreted with caution because of the small sample size and widely overlapping confidence intervals."

Regarding the secondary endpoints of objective response rate (ORR) and disease control rate (DCR), responses were higher with pembrolizumab/chemotherapy versus placebo/chemotherapy, with the greatest treatment effect seen in the CPS ≥10 patients (ORR: 52.7% vs 40.8%, respectively; DCR: 65.0% vs 54.4%).

Duration of response (DOR) was also greater in the pembrolizumab/chemotherapy group, with the longest DOR observed in the CPS ≥10 group (12.8 months vs 7.3 months).

As for safety, 96.3% of patients in the pembrolizumab group and 95.0% of patients in the placebo group had at least one treatment-related adverse event (TRAE) of any grade, while 68.1% and 66.9% of patients in the two arms, respectively, had at least one grade 3-5 TRAE. The most common TRAEs were anemia, neutropenia, and nausea.

There were two TRAEs that led to death in the pembrolizumab arm, while 18.3% of patients in the pembrolizumab arm and 11.0% in the placebo group discontinued treatment due to toxicity.

Immune-mediated AEs occurred in 26.5% of pembrolizumab patients and 6.4% in the placebo group, the most common of which were hypothyroidism and hyperthyroidism.

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