NEW YORK/CHICAGO (Reuters) - Merck & Co’s immunotherapy Keytruda plus chemotherapy significantly improved overall survival in newly-diagnosed patients with advanced non-small cell lung cancer in a closely-watched study, cementing its lead position over Bristol-Myers Squibb Co and others in the most lucrative oncology market.
The survival data sent Merck shares up 2.2 percent to $58.47, while shares of Bristol-Myers plunged 8.4 percent to $53.68 despite positive lung cancer data for its immunotherapy combination in a subset of patients with a high degree of tumor mutations.
The magnitude of the survival benefit in the late-stage study was not yet known, but Keytruda plus chemotherapy cut the risk of death by 51 percent compared with chemotherapy alone, according to data presented at the American Association of Cancer Research meeting in Chicago on Monday.
“The Merck data is pretty much a home run,” said Dr. Roy Herbst, chief of medical oncology at Yale Cancer Center, who was not involved in the study.
“The whole idea (of immunotherapy) would be to avoid chemotherapy. But it works. It’s amazing that we’re going to be bringing these drugs to the majority of patients with lung cancer in the first-line setting,” Herbst added. “Why would you wait and not give someone immunotherapy up front?”
Bristol-Myers’s combination therapy significantly stalled disease progression versus standard chemotherapy in newly-diagnosed advanced non-small cell lung cancer (NSCLC) for patients with a high tumor mutational burden (TMB), a potentially important new biomarker for identifying those most likely to benefit from immunotherapy.
But overall survival is considered the gold standard by doctors and investors, giving Keytruda a clear leg up.
The Keytruda plus chemotherapy regimen was approved as an initial, or first-line, treatment for advanced NSCLC patients based on earlier data from a small study. But many clinicians wanted to see validation of a survival benefit in a large trial.
“We were all waiting to see a definitive Phase III study that showed very clear cut results,” said Dr. Leena Gandhi, the study’s primary investigator and director of thoracic medical oncology at NYU Langone in New York.
Keytruda and Opdivo have piled up approvals for advanced cancers, such as for melanoma and bladder cancer. But those drugs and rival immunotherapies from Roche and AstraZeneca are jockeying for pieces of the largest lung cancer market, especially the coveted newly-diagnosed setting.
There are more than 200,000 new cases of NSCLC each year in the United States alone, with about half at advanced stage at the time of initial diagnosis.
In the Merck-sponsored trial of more than 600 patients called Keynote-189, median overall survival was 11.3 months for chemotherapy, about what was expected. After 12 months, 69.2 percent of patients in the Keytruda group were alive compared with 49.4 percent for chemotherapy, researchers reported.
“We don’t know how long their survival is going to be and we’re excited about that,” said Gandhi.
The differences would likely have been more pronounced, but many patients in the chemotherapy group were given Keytruda or a similar drug once their disease progressed.
Keytruda, with a list price of about $13,500 a month before discounts or rebates, was given every three weeks with a standard chemotherapy regimen. It can be given for up to 24 months for those without disease progression, Merck said.
Dr. Otis Brawley, chief medical and scientific officer for the American Cancer Society, called both trials “incredibly important studies.”
“I worry about cost. A lot of people won’t be able to afford these drugs,” Brawley said.
There was a small increase in acute kidney injury in the Keytruda group compared with chemotherapy alone. There were also three treatment-related deaths from pneumonitis among Keytruda patients.
In the study called CheckMate-227, 43 percent of patients with high TMB who received Opdivo and low-dose Yervoy experienced no disease progression after one year versus 13 percent in the chemotherapy group. There was preliminary evidence of a likely survival benefit but it was too early to determine that, researchers said.
The overall response rate - those with significant tumor shrinkage - was 45 percent for the immunotherapies versus 27 percent for chemotherapy.
Dr. Matthew Hellman of Memorial Sloan Kettering Cancer Center in New York, who led the study, and others said it was a validation of the TMB biomarker.
“Maybe we can look at the TMB and it can further personalize therapy,” said Herbst.
In both studies, positive results were not dependent on cancer cell’s levels of PD-L1, a marker of inflammation that has been commonly used with drugs like Keytruda and Opdivo to help predict patient responses, with higher PD-L1 levels believed to lead to greater efficacy.
“This is great that there’s new options and improved outcomes” for patients with lung cancer, Hellman said.
Reporting by Bill Berkrot; editing by Susan Thomas and Tom Brown