FDA warns of decreased survival in 2 studies of Keytruda, Tecentriq
- The Food and Drug Administration on Friday warned oncologists and clinical trial investigators of early signs from two trials that some bladder cancer patients treated first with either Merck & Co.'s Keytruda or Roche's Tecentriq alone were dying sooner than those given platinum-based chemotherapy.
- Reviews by data monitoring committees overseeing Merck's KEYNOTE-361 and Roche's IMvigor130 observed decreased survival in the monotherapy arm of each study among patients whose tumors expressed low levels of PD-L1, a biomarker associated with response to immunotherapy.
- In an emailed statement, Merck said it had halted enrollment into the monotherapy arm of patients with low PD-L1 expression, but noted the study remains ongoing and no new safety concerns have yet been raised. Roche did not return BioPharma Dive's request for comment before publication.
Keytruda (pembrolizumab) and Tecentriq (atezolizumab) currently carry U.S. approval to treat advanced urothelial carcinoma in previously untreated patients who are ineligible for cisplating-containing chemo, or who have progressed following initial treatment with platinum-based chemo.
For both drugs, use in the first-line setting was granted on an accelerated basis, meaning Merck and Roche need to conduct further study to confirm the initial data that led to the FDA OK.
KEYNOTE-361 and IMvigor130 are similar studies, testing each company's respective checkpoint inhibitor with and without platinum-based chemotherapy against chemo alone. Crucially, the trials are enrolling patients who are eligible for this type of chemo — different from the studies in cisplatin-ineligible patients which led to the initial first-line nod for the drugs.
The FDA recommends that, outside of the clinical trial setting, physicians select patients for treatment with either drug based on the current approvals.
A federal database lists the primary completion date for Roche's study as the end of this year, while Merck's study is currently scheduled to reach primary completion by June of 2019.
Roche was actually the first to secure an approval for a checkpoint inhibitor in bladder cancer, aiming at the indication first in hopes of carving out a market niche before Merck and rival Bristol-Myers Squibb could make inroads.
Merck, however, has since made up ground and estimates by Cowen, an investment firm, put Merck ahead of Roche in market share.
The company estimates about 5% of its sales of Keytruda come from its indications in bladder cancer. Using the drug's first quarter sales of $1.46 billion would put bladder cancer revenues at about $73 million.
Roche, on the other hand, estimates about 40% of its U.S. sales of Tecentriq come from bladder cancer. Globally, Tecentriq earned 139 million Swiss francs over the first three months of the year, or about $139 million.
The FDA warning comes about a year after Roche revealed a Phase 3 study called IMvigor211 failed, showing second-line treatment with Tecentriq monotherapy did not extend survival versus another type of chemotherapy.
- Food and Drug Administration MedWatch notice
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