Merck & Co. reported Tuesday that in the final analysis of the Phase III KEYNOTE-355 trial, first-line Keytruda (pembrolizumab) plus chemotherapy led to a significant and clinically meaningful improvement in overall survival (OS) compared to chemotherapy alone in patients with metastatic triple-negative breast cancer (TNBC) whose tumours express PD-L1 with a combined positive score (CPS) ≥10. The company noted that Keytruda is the first anti-PD-1 therapy in combination with chemotherapy to demonstrate a significant OS benefit for this patient population.
In an earlier interim analysis, the combination significantly improved progression-free survival (PFS) in these higher-expressing PD-L1 patients, reducing the risk of disease progression or death by 35% compared with chemotherapy alone. However, the combination fell short of statistical significance for PFS in those whose tumours express PD-L1 with a CPS ≥1.
KEYNOTE-355 included 847 patients with locally recurrent inoperable or metastatic TNBC that has not been previously treated with chemotherapy in the advanced setting. Patients were randomised to receive Keytruda or placebo, both in combination with investigator's choice of chemotherapy. The trial's dual primary endpoints are PFS and OS in patients expressing PD-L1 CPS ≥1 and CPS ≥10, and in the intention-to-treat population. Other study goals are assessing objective response rate, duration of response and disease control rate.
Merck said these new OS results will be presented at an upcoming medical meeting and submitted to regulatory authorities.
The trial update coincides with Merck obtaining FDA approval for a broader TNBC label that now includes high-risk early-stage patients. Keytruda was already cleared via an accelerated pathway for use with chemotherapy to treat locally recurrent unresectable or metastatic TNBC tumours expressing PD-L1 CPS ≥10, and that approval was converted to a full approval on Tuesday.
For related analysis, read Physician Views Results: Early-stage TNBC data for Keytruda gets resounding thumbs up, and KOL Views Q&A: Keynote-522 is new SOC in early-stage TNBC, but Tecentriq not out of the race, says leading oncologist.
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