With at least one gastric cancer approval on the line, Merck's Keytruda scores nod for early patients in chemo combo
Big drugmakers such as Merck and Bristol Myers Squibb are on the firing line with the FDA over accelerated oncology approvals that don’t ace their confirmatory trials. While Keytruda is in the FDA’s sights for third-line gastric cancer patients, it will add a new approval in combination with chemo for earlier use.
The FDA approved Merck’s Keytruda as a combination therapy with platinum- and fluoropyrimidine-based chemotherapy to treat first-line patients with metastatic esophageal cancer or gastroesophageal junction carcinoma whose tumors can’t be removed and aren’t suitable for radiation, the New Jersey pharma said Monday.
The agency based its review on data from the Phase III KEYNOTE-590 trial, which found that a combination of Keytruda, fluorouracil and cisplatin topped fluorouracil and cisplatin alone in terms of extending patients’ lives.
The Ketyruda combo cut the risk of death by 27% over the chemo control arm and sliced the risk of disease progression or death by 35%. The combo posted an ORR of 45% compared with 29% in the control arm. Those findings were consistent regardless of patients’ tumor histology or PD-(L)1 expression.
Esophageal cancer is the sixth-leading cause of cancer death in the US with roughly 19,000 new cases reported each year, Merck said.
Taking a first-line win in esophageal cancer and GEJ is a big win given the “few advances in improving survival outcomes” in that setting over the past few decades, Merck Research Laboratories’ CMO Roy Baynes said in a statement. But the approval will cast an even brighter spotlight on Keytruda’s accelerated nod in gastric cancer and GEJ in third-line or later patients.
In April, the FDA’s Oncology Center of Excellence will hold a three-day review of targeted accelerated approvals, including a snap approval granted back in September 2017 for Keytruda in patients who previously received two rounds of platinum- or fluoropyrimidine-based chemo. That approval was based on results from the KEYNOTE-059 study, part of Merck’s expansive gastric cancer program for Keytruda to snare a suite of early- and later-line indications for the checkpoint inhibitor.
The FDA has launched what it’s calling an “industry-wide evaluation” of its accelerated approval pathway after a series of drugmakers flopped the confirmatory trials for OS and PFS on which the early decisions were based. Keytruda fell victim there in February, with Merck pulling its marketing approval to treat patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. Both Bristol Myers Squibb with Opdivo and AstraZeneca with Imfinzi have faced the FDA’s ire as well.
With that review approaching, Merck is looking to steady the boat for as many Keytruda decisions as it can. Last week, the drugmaker touted new data showing a Keytruda-Lenvima combo nailed its primary progression-free survival and OS endpoints in an open-label Phase III study in advanced, metastatic or recurrent endometrial cancer patients after chemo. The confirmatory KEYNOTE-775 study broke patients down into two main subgroups based on their mismatch repair status, a key biomarker in determining whether a specific case of endometrial cancer is hereditary.