Final results of the KEYNOTE-355 trial support the use of a combined positive score (CPS) of 10 or higher as a reasonable PD-L1 expression cut-off to define the population of patients with metastatic triple-negative breast cancer (TNBC) expected to derive benefit from pembrolizumab plus chemotherapy.
Results of KEYNOTE-355 were presented at the 2021 San Antonio Breast Cancer Symposium (SABCS) by Javier Cortes, MD, PhD of International Breast Cancer Center, Madrid and Barcelona, Spain.
In the primary analysis of KEYNOTE-355 trial, pembrolizumab plus chemotherapy significantly improved overall survival and progression-free survival compared with placebo plus chemotherapy in patients with previously untreated, locally recurrent, inoperable or metastatic TNBC that expressed PD-L1 with a CPS score of 10 or higher. There was no significant difference in tumors with a CPS score of 1 or higher.
The trial included 847 patients who were randomly assigned 2:1 to pembrolizumab plus chemotherapy or chemotherapy alone.
In the primary analysis of the study, the hazard ratios (HRs) for overall survival were 0.73 for CPS ≥10 subgroup, 0.86 for the CPS ≥1 subgroup, and 0.89 for the intent-to-treat (ITT) population. Similarly, progression-free survival HRs were best in the CPS ≥10 subgroup at 0.66; progression-free survival HRs were 0.75 for the CPS ≥1 subgroup and 0.82 for the ITT group.
At the meeting, Cortes presented results of a subgroup analysis that assessed outcomes in subgroups of patients by different CPS cutoffs.
Overall survival results were similar in the subgroups with CPS scores of less than 1 and 1 to 9 for pembrolizumab plus chemotherapy and placebo plus chemotherapy. However, results showed treatment benefit when pembrolizumab was added in the CPS 10-19 (HR=0.71; 95% CI, 0.46-1.09) and CPS ≥20 (HR=0.72; 95% CI, 0.51-1.01) subgroups, suggesting “that CPS ≥10 could be a reasonable cutoff,” Dr Cortes said.
In the CPS 10-19 and CPS ≥20 subgroups, there was sustained separation of the overall survival curves starting at approximately 10 months.
The subgroup analysis for progression-free survival revealed a trend toward improved efficacy with the addition of pembrolizumab. In the CPS 10-19 and CPS ≥20 subgroups, progression-free survival curves had more sustained separation beginning at approximately 4 months. The HRs for the 2 groups were 0.70 and 0.62, respectively.
The majority of patients in both arms experienced treatment-related adverse events. Adverse events grades 3 to 5 were reported in 68.1% of patients assigned to pembrolizumab and 66.9% of patients assigned to chemotherapy alone. Two patients in the pembrolizumab arm died. Immune-mediated adverse events grades 3 to 5 occurred in 5.3% of patients assigned to pembrolizumab and 0% of patients assigned to chemotherapy alone.
“In my opinion, these results provide further support for pembrolizumab in combination with chemotherapy as a good option and standard of care for some patients with recurrent, unresectable or metastatic TNBC whose tumors express PD-L1 with a CPS or 10 or more,” Dr Cortes concluded.
Disclosures: This research was supported by Merck & Co, Inc. One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
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Cortes J, Cescon DW, Rugo HS, et al. Final results of KEYNOTE-355: randomized, double-blind, phase 3 study of pembrolizumab + chemotherapy vs placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. Presented at: SABCS 2021; December 7-10, 2021; San Antonio, TX. Abstract GS1-02.