medwireNews: Adding pembrolizumab to chemotherapy significantly improves the overall survival (OS) of people with advanced triple-negative breast cancer (TNBC) and a tumoral PD-L1 combined positive score of at least 10 (CPS-10), demonstrate phase 3 trial data.
There was no such significant OS benefit among participants with a CPS of 1 or more, however, which precluded “formal testing in the intention-to-treat [ITT] population,” say Javier Cortes (International Breast Cancer Center, Barcelona, Spain) and fellow KEYNOTE-355 researchers.
They continue: “Our results build on findings from earlier trials involving patients with metastatic [TNBC] that showed greater single-agent activity with pembrolizumab and other immune checkpoint inhibitors with increasing PD-L1 expression.”
A prespecified interim analysis from the double-blind study comprising 847 participants a significant improvement in the co-primary endpoint of progression-free survival with the addition of pembrolizumab 200 mg every 3 weeks to investigator’s choice of chemotherapy in the CPS-10 but not CPS-1 subgroup.
The current report focuses on the final analysis of the other primary endpoint – OS – and is published in The New England Journal of Medicine.
After a median follow-up of 44.1 months, median OS in the CPS-10 patients was 23.0 months with pembrolizumab plus chemotherapy and 16.1 months with placebo plus chemotherapy. The between-group difference was significant and equated to a hazard ratio (HR) for death of 0.73.
The estimated OS rates at 18 months were 58.3% and 44.7%, respectively.
By contrast, the median OS times in the CPS-1 subgroup were comparable regardless of whether pembrolizumab or placebo was added to chemotherapy, at 17.6 and 16.0 months, respectively, and the HR for death was a nonsignificant 0.86. At the 18-month mark, a respective 48.4% and 41.4% of patients were estimated to be alive.
In the ITT population, OS was a median of 17.2 months in the pembrolizumab arm and 15.5 months in the placebo arm, and “[s]ignificance was not tested because of the prespecified multiplicity strategy,” say the study authors.
They add that the updated progression-free survival and objective response results are “consistent with the previous interim data,” as are the safety data, “with no new safety signals” after longer follow-up.
Treatment-related adverse events of grade 3 or worse occurred in a comparable 68.1% of pembrolizumab-treated patients and 66.9% of those given placebo, with immune-mediated events of grade 3 or 4 occurring in 5.3% and 0.0%, respectively.
“The most frequent adverse events related to the trial regimen in both groups (anemia, neutropenia, and nausea) reflect toxic effects typically associated with chemotherapy, and the addition of pembrolizumab did not increase the incidence of these adverse events or compromise exposure to chemotherapy,” highlights the research team.
In a related editorial, Xavier Pivot (Institute of Cancerology Strasbourg, France) describes the pembrolizumab findings in patients with TNBC and a PD-L1 CPS of 10 or more as a “breakthrough.”
He continues: “This new class of immunotherapy is integral to the success of biologic agents and marks the continued improvement of breast cancer treatment.
“Other immunotherapies will emerge, but pembrolizumab will remain the first treatment shown to prolong overall survival, a welcome and definitive change in the treatment of a subgroup of women with advanced triple-negative breast cancer.”
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