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UK's NICE Recommends Against Merck's Keytruda, Chemo Combo for Advanced PD-L1-Positive TNBC

NEW YORK – The UK's National Institute for Health and Care Excellence on Tuesday recommended against making Merck's Keytruda (pembrolizumab) plus chemotherapy available in England for advanced, PD-L1-positive triple-negative breast cancer patients who have not had prior chemotherapy.

In a draft guidance for public consultation, NICE said that the long-term benefit of the treatment combination is unclear. Additionally, the agency noted that there is no direct evidence from clinical trials showing that Keytruda plus chemo is superior to Genentech's Tecentriq (atezolizumab) plus chemo, a combination that NICE already recommends in this setting.

Additionally, the cost-effectiveness estimates for the Keytruda-chemo combo exceed what NICE considers an acceptable use of National Health Service England's resources. Keytruda's list price is £2,630 ($3,452) per infusion vial, though Merck had proposed to provide the agent to the NHS at an undisclosed discount.

In drafting its recommendation, NICE considered data from the Phase III KEYNOTE-355 trial, in which treatment-naive metastatic TNBC patients received either the Keytruda-chemo combination or chemo alone. Of 847 patients, 38 percent had tumors expressing PD-L1 with combined positive scores, or CPS, of at least 10. In that trial, Merck reported that the immunotherapy combination reduced patients' risk of death by 27 percent versus chemotherapy alone.

However, because Tecentriq-chemo is a treatment option in this setting as well, NICE felt that KEYNOTE-355's chemo-alone comparator was insufficient. Merck conducted a meta-analysis to try to show the Keytruda regimen had benefits over the Tecentriq cocktail, but NICE was not swayed by the indirect trial comparison. Key differences between these trials, including the fact that Tecentriq's registrational trial — IMpassion130 — measured PD-L1 positivity differently, made it challenging for NICE to draw definitive conclusions about the benefit of the Keytruda-chemo regimen.

The US Food and Drug Administration, in contrast, relied on KEYNOTE-355 to approve Keytruda-chemo for advanced TNBC patients with PD-L1 CPS 10 or above. The agency first granted accelerated approval for the indication in November 2020, then converted it to a full approval in July 2021. The European Commission has also approved the combo for this indication.

Helen Knight, program director of the NICE Center for Health Technology, said in a statement that the agency is working with Merck to "try to resolve the issues identified by the committee."