Merck & Co.'s Keytruda gains first breast cancer indication with new FDA approval

The FDA announced Friday that it awarded accelerated approval to Merck & Co.'s Keytruda (pembrolizumab) for use in combination with chemotherapy to treat patients with locally recurrent, unresectable or metastatic triple-negative breast cancer (TNBC) whose tumours express PD-L1 with a combined positive score (CPS) of 10 or greater. The company filed the supplemental biologics application for Keytruda in this indication at the end of July, along with another seeking approval of the anti–PD-1 therapy for patients with high-risk early-stage TNBC.

"Today's approval is a significant milestone, as it represents the first approval for Keytruda in the breast cancer setting," remarked Roy Baynes, head of global clinical development and chief medical officer at Merck Research Laboratories.

The decision was based on results from the Phase III KEYNOTE-355 study testing Keytruda in combination with chemotherapy, against placebo plus chemotherapy, as a first-line treatment for patients with metastatic TNBC. Detailed findings unveiled in May showed that among patients whose tumours expressed PD-L1 with CPS of at least 10, Keytruda led to significant and clinically meaningful improvement in progression-free survival (PFS), reducing the risk of disease progression or death by 35% and improving PFS to a median of 9.7 months, compared to 5.6 months for those on chemotherapy alone.

For patients whose tumours expressed PD-L1 with CPS of 1 or more, Keytruda was associated with a median PFS of 7.6 months, versus 5.6 months for the placebo group, although this did not meet statistical significance. Merck said in May that the trial would continue without changes to evaluate the other dual primary endpoint of overall survival.

Second TNBC filing under review

Meanwhile, the Keytruda filing for high-risk early-stage TNBC, which is based on results from the KEYNOTE-522 trial, remains under review with a decision date set for March 29 of next year. Data from that study, unveiled in 2019, showed that pathological complete response (pCR) in patients with early TNBC significantly increased from 51.2% in the placebo plus chemotherapy group to 64.8% among those given Keytruda in combination with chemotherapy.

This past June, Roche reported results from the Phase III IMpassion031 study demonstrating that its PD-L1 inhibitor Tecentriq (atezolizumab) plus chemotherapy met the primary endpoint of pCR in patients with early TNBC regardless of PD-L1 expression. Tecentriq in combination with Bristol Myers Squibb's Abraxane (nab-paclitaxel) is currently approved in more than 70 countries worldwide, including the US and Europe, for adults with unresectable, locally advanced or metastatic TNBC whose tumours express PD-L1.

For related analysis, see KOL Views Results: Keytruda, Tecentriq remain neck and neck in adjuvant TNBC, says leading oncologist.

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