Kaiser Permanente clinical trial also shows genetic biomarkers can help predict who responds best to therapy.
OAKLAND, Calif. — In global clinical trials, patients with advanced metastatic lung cancer who were treated with a targeted immunotherapy drug lived significantly longer and with fewer side effects than those who received standard second-line chemotherapy, according to a new Kaiser Permanente study published today in the journal The Lancet.
"The results of this study demonstrate that the use of atezolizumab, a monoclonal antibody, improves the survival rate of a majority of lung cancer patients who have progressive cancer when used after first-line chemotherapy,” said lead author Louis Fehrenbacher, MD, medical director of Kaiser Permanente Oncology Clinical Trials.
Atezolizumab is an experimental drug developed by the pharmaceutical company F. Hoffman-La Roche/Genentech, which sponsored the randomized clinical trial. Not currently approved by the Food and Drug Administration, this drug is one of a new class of genetically engineered antibodies that reduce the cancer’s ability to evade the natural immune reaction to many lung cancers.
“These drugs boost the immune system, unleashing it to attack the cancer,” Dr. Fehrenbacher said. “The findings of this study contribute to a growing body of evidence that shows that genetic biomarkers can help predict who responds the best to this therapy, moving oncology further down the path toward personalized, targeted medicine.”
A total of 287 patients were enrolled in the large phase II clinical trial from 61 sites in 13 countries — including 16 Kaiser Permanente members in Northern California — between August 2013 and March 2014. All patients had advanced metastatic, non-small-cell lung cancer (either squamous or non-squamous) that had been previously treated with at least one course of chemotherapy. Genetic profiling of their tumors identified an immune-system protein called PD-L1, which indicates potential receptiveness to the immune-system treatment.
One group of 144 patients received the immunotherapy atezolizumab, while the other 143 patients received docetaxel, a standard chemotherapy that works by interfering with cell division. Treatments were administered intravenously every 21 days, for as long as patients were receiving clinical benefits.
At a minimum follow-up of 13 months after beginning treatment, patients receiving the experimental drug had an average overall survival rate of 12.6 months, versus 9.7 months for patients who had received the standard chemotherapy drug. Twelve of those who received atezolizumab still had an ongoing response to the drug at that time versus five of those receiving docetaxel. At 20 months after the initiation of treatment, approximately twice as many people on the experimental drug survived than those on the standard chemotherapy drug.
Despite being on the immune-system treatment for longer periods of time, patients receiving the experimental drug were less likely to experience serious side effects than those receiving the standard chemotherapy drug (40.1 percent versus 52.6 percent, respectively). “Atezolizumab was well tolerated with a safety profile consistent with previous studies, and no new safety signals were observed,” the study authors wrote.
The clinical trial also showed that lung cancer patients who had the immune-system protein PD-L1 biomarker were significantly more likely to respond to the atezolizumab treatment, and survive longer. Two-thirds of lung cancers in this trial expressed PDL-1 on either their cancer cells or immune cells, which means that the normal immune response had been activated.
Since Kaiser Permanente Oncology Clinical Trials began enrolling its first patients in trials for cancer treatment more than 25 years ago, the program has grown to be one of the nation’s largest; in 2014, Kaiser Permanente became a National Cancer Institute Community Oncology Research Program. In addition to the lung cancer trials, Kaiser Permanente has been actively enrolling patients in trials evaluating immune therapies for melanoma, a specific type of breast cancer, and bladder cancer, and has trials being activated for other cancer types.
Dr. Fehrenbacher and all study co-authors are members of the atezolizumab study group, including researchers from U.S. Oncology Research, Virginia Cancer Specialists Research Institute, Genentech, University Hospitals KU Leuven (Belgium), Toulouse University Hospital (France), Samsung Medical Centre (South Korea), Compass Oncology (Canada), Hospital Universitario Miguel Servet (Spain), Charing Cross Hospital (U.K.), Comprehensive Cancer Centers of Nevada, and Lugenfachklinik Immernhausen (Germany).
The study was sponsored by F. Hoffman-La Roche/Genentech.
The Kaiser Permanente Division of Research conducts, publishes, and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and society at large. It seeks to understand the determinants of illness and well-being, and to improve the quality and cost-effectiveness of health care. Currently, DOR’s 500-plus staff is working on more than 400 epidemiological and health services research projects. For more information, visit www.dor.kaiser.org or follow us @KPDOR.
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