First-Line Pembrolizumab Plus Chemotherapy Improved PFS in PD-L1–Positive mTNBC

Combining pembrolizumab with chemotherapy resulted in significant improvements in progression-free survival compared with chemotherapy alone among women with previously untreated PD-L1–positive metastatic triple-negative breast cancer (TNBC), according to results from the KEYNOTE-355 trial.

“These findings suggest a role for the addition of pembrolizumab to standard chemotherapy for the first-line treatment of metastatic TNBC,” said Javier Cortes, MD, of Ramón y Cajal University Hospital, Madrid, Spain, who presented the results as part of the ASCO20 Virtual Scientific Program.

KEYNOTE-355 randomly assigned 847 previously untreated patients in a 2:1 ratio to receive pembrolizumab plus chemotherapy (investigator’s choice of nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin) or placebo plus chemotherapy. Dual primary endpoints were progression-free and overall survival in patients with PD-L1–positive tumors. Crossover was not allowed. Outcomes were examined among patients with a combined positive score (CPS) or 10 or greater and a CPS of 1 or greater. However, patients were eligible for the study regardless of PD-L1 expression.

The median follow-up for patients assigned to receive pembrolizumab was 17.5 months; it was 15.5 months for the placebo arm.

The pembrolizumab combination significantly improved progression-free survival in patients with CPS of 10 or greater. The median progression-free survival was 9.7 months for pembrolizumab plus chemotherapy compared with 5.6 months for chemotherapy alone (hazard ratio [HR], 0.65; 95% CI, 0.49-0.86; P =.0012). At 12 months, progression-free survival was 39.1% for the pembrolizumab arm compared with 23% for placebo.

Among patients with CPS of 1 or greater, 67.8% of patients and almost 77% of patients in the placebo group had experienced disease progression or death. The median progression-free survival was 7.6 months for pembrolizumab plus chemotherapy compared with 5.6 months for the placebo plus chemotherapy arm (HR, 0.74; 95% CI, 0.61-0.90; P =.0014).

“However, according to the prespecified statistical criteria, there was no statistically significant difference between treatment groups in patients with CPS 1 or higher,” Dr Cortes said during the video presentation.

Among the entire intention-to-treat population, the median progression-free survival was 7.5 months pembrolizumab plus chemotherapy compared with 5.6 months for chemotherapy plus placebo (HR, 0.82; 95% CI, 0.69-0.97). Statistical significance was not tested in the ITT population, Dr Cortes said.

The evaluation of overall survival is still ongoing.

More than 60% of patients assigned to pembrolizumab plus chemotherapy (68.1%) or placebo plus chemotherapy (66.9%) experienced grade 3 to 5 adverse events. Two deaths occurred in the pembrolizumab arm because of treatment-related adverse events. Additionally, 5.2% of patients assigned to be administered pembrolizumab had grade 3 or higher immune-related adverse events.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2020 meeting by visiting the conference page.

Reference

Cortes J, Cescon DW, Rugo HS, et al. KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 1000.