Pembrolizumab indication reversed after accelerated approval for SCLC

Lung cancer

By Mardi Chapman

16 Mar 2021

Pembrolizumab has been withdrawn from treatment of metastatic SCLC in the US after post-marketing data failed to confirm the early study benefits that won it FDA accelerated approval two years ago.

Merck, in consultation with the FDA, has voluntarily withdrawn its anti-PD-1 therapy (Keytruda) for the treatment of patients with metastatic small cell lung cancer (SCLC) that has progressed.

The monoclonal antibody had received accelerated approval in June 2019 based on the tumour response rate and durability of response data from KEYNOTE-158 (cohort G) and KEYNOTE-028 (cohort C1).

However the continued approval for this indication was contingent upon completion of the post-marketing requirement establishing superiority of pembrolizumab as determined by overall survival (OS).

As announced in January 2020, KEYNOTE-604, the confirmatory phase 3 trial for this indication, met one of its dual primary endpoints of progression-free survival but did not reach statistical significance for the other primary endpoint of OS.

“Merck’s consultation with the FDA on this withdrawal is part of an industry-wide evaluation of indications based on accelerated approvals that have not yet met their post-marketing requirements,” the company said.

“This decision does not affect other indications for Keytruda,” it said.

“Keytruda remains a foundational treatment for certain patients with metastatic non-small cell lung cancer. We will continue to rigorously evaluate the benefits of Keytruda in small cell lung cancer and other types of cancer,” Merck’s senior vice president and head of global clinical development Dr Roy Baynes said.

Professor Michael Boyer, chief clinical officer at Chris O’Brien Lifehouse, told the limbic the withdrawal of pembrolizumab had minimal implications in Australia where it was not being used for this indication.

“The checkpoint inhibitor that is used in small cell in Australia is atezolizumab, which is both approved and reimbursed on the PBS. This has been shown to improve both PFS and OS in a study called IMpower 133,” he said.

Bristol Myers Squibb had a similar experience to Merck with approval for their immune checkpoint inhibitor nivolumab (Opdivo) for patients with SCLC whose disease had progressed after platinum-based chemotherapy and at least one other line of therapy.

It had also received an accelerated FDA approval in 2018 but was withdrawn in late 2020 for failing to meet the OS endpoint.

Already a member?

Login to keep reading.

Email me a login link