Merck & Co. unveiled updated study results demonstrating that adding Keytruda (pembrolizumab) to chemotherapy in the first-line setting reduced the risk of death by 27%, 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. Detailed findings from the Phase III KEYNOTE-355 trial were presented Sunday at the European Society for Medical Oncology (ESMO) congress.
The OS data were top-lined in July after Merck had said the combination met the study's other main goal of progression-free survival (PFS) in these higher-expressing PD-L1 patients, cutting the likelihood of disease progression or death by 35% over chemotherapy alone. However, it missed the bar of statistical significance in those with a CPS ≥1. The data nevertheless supported US and Japanese approval of the regimen in TNBC.
KEYNOTE-355 included 847 patients with locally recurrent inoperable or metastatic TNBC that has not been previously treated with chemotherapy in the advanced setting. Participants were randomised to Keytruda or placebo, both administered together with investigator's choice of chemotherapy, including nab-paclitaxel, paclitaxel or gemcitabine-carboplatin. Study endpoints included OS and PFS in patients whose tumours express PD-L1 with CPS ≥1 or CPS ≥10.
Median OS for the higher PD-L1 expressers treated with Keytruda plus chemotherapy was 23 months, versus 16.1 months for placebo. The trial was not powered to make efficacy comparisons between treatment groups by chemotherapy regimen, but Merck said the OS increase seen with Keytruda occurred across the three different chemotherapy choices. In addition, these CPS ≥10 patients achieved median PFS of 9.7 months, compared to 5.6 months for placebo.
Lower-expressing PD-L1 patients achieved median OS of 17.6 months and PFS 7.6 months. As was the case with PFS, there was no significant difference in OS between treatment groups among CPS ≥1 patients. Meanwhile, on the secondary endpoint of objective response rate (ORR), Keytruda-treated patients with CPS ≥10 achieved a response of 52.7%, while ORR for the CPS ≥1 group was 44.9%.
Keytruda was originally cleared last November via an accelerated pathway for use with chemotherapy to treat locally recurrent unresectable or metastatic TNBC tumours expressing PD-L1 CPS ≥10. The FDA recently converted that to a full approval, and at the same time also expanded the drug's label to include high-risk early-stage TNBC based on results from the Phase III KEYNOTE-522 study.
Late last month, Roche voluntarily withdrew its immunotherapy Tecentriq (atezolizumab) for the treatment of PD-L1-positive, metastatic TNBC in the US market, citing "recent changes" in the treatment landscape. The drug, which became the first immunotherapy to be cleared for metastatic TNBC when it won an accelerated approval in 2019, failed to show a survival benefit in the post-marketing IMpassion131 trial.
For related analysis, see ViewPoints: Keynote-355 hammers home Keytruda's advantage in TNBC.
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