Pembrolizumab SCLC Indication Withdrawn in US

Was Accelerated Approval

Nick Mulcahy

March 04, 2021

Merck & Co is withdrawing the US indication for pembrolizumab (Keytruda) for metastatic small cell lung cancer (SCLC) in patients with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy, according to a company statement.

The move does not affect any of the drug's other indications: the immunotherapy is used in the treatment of many different types of cancer.

The SCLC indication had been granted an accelerated approval by the Food and Drug Administration (FDA) in 2019 based on tumor response rate and durability of response data from patient cohorts in two trials. However, the anti-PD-1 therapy failed to demonstrate statistically significant improved overall survival in a confirmatory trial, which is mandated after an accelerated approval.

The FDA is conducting "an industry-wide evaluation of indications based on accelerated approvals that have not yet met their post-marketing requirements," said Merck.

Three weeks ago, an indication for durvalumab (Imfinzi) was withdrawn by AstraZeneca in concert with the FDA after the drug failed to improve overall survival in unresectable metastatic bladder cancer in a confirmatory trial, as reported by Medscape Medical News.

"We will continue to rigorously evaluate the benefits of [pembrolizumab] in small cell lung cancer and other types of cancer, in pursuit of Merck's mission to save and improve lives," said Roy Baynes, MD, chief medical officer, Merck Research Laboratories, in the company statement

Baynes also championed the value of accelerated approvals.

"The accelerated pathways created by the FDA have been integral to the remarkable progress in oncology care over the past 5 years and have helped many cancer patients with advanced disease, including small cell lung cancer, access new treatments," he commented.

However, in the past, the FDA has been criticized for approving new cancer drugs based on surrogate markers such as response rates because, in many cases, subsequent studies often show that the drug fails to improve overall survival.

For example, a 2015 study found that 36 of 54 (67%) cancer drug approvals from 2008 to 2012 were made on the basis of surrogate markers — either tumor response rate or progression-free survival. Over a median follow-up period of 4.4 years, only 5 of those 36 drugs were shown, in randomized studies, to improve overall survival, as reported by Medscape Medical News.

The FDA says that it instituted the accelerated approval program to "allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint." The program was started in 1992, in the midst of the HIV/AIDS epidemic.

Last year, the nonprofit Friends of Cancer Research issued a white paper calling for reform in the accelerated approval process, which included a proposal to add risk assessment to surrogate endpoints that would factor in variables such as toxicity.

Nick Mulcahy is an award-winning senior journalist for Medscape. He previously freelanced for HealthDay, MedPageToday and has had bylines on, MSNBC, and Yahoo. Email: and on Twitter: @MulcahyNick

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