By Bill Berkrot
April 16 (Reuters) - Merck & Co's immunotherapy Keytruda plus chemotherapy significantly improved overall survival versus chemotherapy alone in newly-diagnosed patients with advanced non-small cell lung cancer in a highly-anticipated study that appears to cement the company's lead in the most lucrative oncology market.
While magnitude of the survival benefit in the late-stage study was not yet known, the Keytruda combination cut the risk of death by 51 percent compared with chemotherapy and significantly delayed disease worsening, according to data presented on Monday.
"This study showed a clear difference in long-term outcomes," said Dr. Leena Gandhi, the study's primary investigator, who called the results "practice changing."
In another closely-watched study, a combination of Bristol-Myers Squibb's immunotherapy drugs Opdivo and Yervoy significantly stalled disease progression versus standard chemotherapy in newly-diagnosed advanced non-small cell lung cancer (NSCLC) for patients whose tumors had a high number of genetic mutations. Tumor mutational burden (TMB) is a potentially important new biomarker for identifying those most likely to benefit from immunotherapy.
The results were presented at the American Association of Cancer Research meeting in Chicago.
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. Thus far, Merck is dominating 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.
The Keytruda plus chemotherapy regimen was approved as an initial, or first-line, treatment for advanced 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 Gandhi, director of thoracic medical oncology at NYU Langone in New York.
In both studies, the 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.
In the Merck-sponsored trial called Keynote-189, median overall survival was 11.3 months for chemotherapy but not yet reached for the Keytruda combination. "We don't know how long their survival is going to be and we're excited about that," Gandhi said.
After 12 months, 69.2 percent of patients in the Keytruda group were alive compared with 49.4 percent for chemotherapy, researchers reported.
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.
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. After one year, 68 percent of responders to Opdivo and Yervoy continued to benefit from the therapy.
Dr. Matthew Hellman of Memorial Sloan Kettering Cancer Center in New York, who led the study, said it was a validation of TMB as a biomarker and that Opdivo with Yervoy should be an important chemotherapy-sparing regimen in first-line lung cancer.
"This is great that there's new options and improved outcomes," Hellman said of the two studies. "That's tremendous progress for patients with lung cancer." (Reporting by Bill Berkrot; editing by Diane Craft)
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