Merck bags imperfect immunotherapy first with Keytruda cervical cancer approval

Keytruda
The FDA approval for Keytruda in first-line cervical cancer has helped convert an accelerated approval in the second-line setting into a full one. (Merck)

Merck & Co. is adding yet another immuno-oncology first under Keytruda’s belt. But the breadth of the win comes out less than ideal.

The FDA has backed Keytruda’s use alongside chemotherapy, with or without Roche’s Avastin, for treating patients with persistent, recurrent or metastatic cervical cancer but only for those whose tumors express the PD-L1 biomarker at a combined positive score (CPS) of at least 1.

Although the go-ahead makes Keytruda the first PD-1/L1 inhibitor for first-line treatment of cervical cancer, the PD-L1 restriction comes despite the drug showing a survival benefit in an analysis of a broader patient population.

Adding Keytruda to chemotherapy—with or without Avastin—cut the risk of death by 33% in a phase 3 trial in first-line cervical cancer, according to data unveiled at ESMO 2021. Based on the showing, SVB Leerink analyst Daina Graybosch projected Keytruda sales in metastatic cervical cancer at $114 million in 2025 out of a $174 million total for all PD-1/L1s.

RELATED: ESMO: Merck details Keytruda's 'practice-changing' cervical cancer survival win

A subgroup analysis of the phase 3 Keynote-826 trial did show that in a small group of patients with PD-L1 CPS less than 1, Keytruda didn’t offer any additional survival or tumor progression benefits. Drugmakers often shrug off lackluster showings in small subgroups, pointing to their lack of statistical powering and the trial design to cover a more inclusive population. But in this case, data from this subgroup seemed to have mattered for Keytruda’s final label even though only 69 patients belonged to it. 

A Merck spokesperson confirmed to Fierce Pharma that the company originally asked for an all-comers indication, but the FDA restricted the final label based on its assessment of PD-L1 expression subgroups.

When considering just patients with PD-L1 CPS of 1 or more, Keytruda’s death risk reduction increased to 36%. Patients in the control arm lived a median 16.3 months, while median overall survival wasn’t reached among patients who got the Merck drug.

RELATED: Sanofi, Regeneron's Libtayo looks for new cervical cancer use with first-in-class survival win

Thanks to an accelerated approval the FDA doled out in 2018, Keytruda has been allowed as a single agent for cervical cancer with disease progression on or after chemotherapy in patients with PD-L1 CPS of at least 1. Wednesday’s approval has helped convert that conditional nod into a full approval.

Meanwhile, Regeneron and Sanofi’s Libtayo is currently under FDA priority review for previously treated cervical cancer with a regulatory decision expected on Jan. 30, 2022. In its Empower-Cervical 1 trial, Libtayo monotherapy pared down the risk of death by 31% over chemotherapy in second-line cervical cancer regardless of PD-L1 status.

Editor's Note: The story has been updated with additional info from a Merck spokesperson.