In global clinical trials, patients with advanced, metastatic lung cancer who were treated with a targeted immunotherapy drug lived significantly longer with fewer side effects than those who received standard second-line chemotherapy, according to a new study published today in the journal The Lancet.
"The results of this study demonstrate that the use of atezolizumab, a monoclonal antibody, improves survival of a majority of lung cancer patients that have progressive cancer when used after first-line chemotherapy,” said lead author Louis Fehrenbacher, MD, medical director of Kaiser Permanente Oncology Clinical Trials. “It also shows that genetic biomarkers can help predict who responds the best to this therapy.”
Atezolizumab is an experimental drug developed by the pharmaceutical company F. Hoffman-La Roche/Genentech, which sponsored the randomized clinical trial, called POPLAR. Not currently approved by the Food and Drug Administration, atezolizumab 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,” Fehrenbacher said.
Patients were enrolled in the large phase II clinical trial from 61 sites in 13 countries — including 16 members of Kaiser Permanente NCal — 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. The tumors were profiled for the genetic expression of an immune-system protein called PD-L1, which indicates potential receptiveness to the immune-system treatment.
One group of 144 patients received the immune-system therapy 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 the initiation of treatment, patients receiving atezolizumab had an average overall survival rate of 12.6 months, versus 9.7 months with docetaxel. Twelve of those who received atezolizumab still had an ongoing response to the drug at the last recent analysis, versus five of those receiving docetaxel. At 20 months after the initiation of treatment, approximately twice as many people on atezolizumab survived than those on docetaxel.
Despite longer time on of treatment, patients receiving atezolizumab were less likely to experience serious side effects than those receiving docetaxel (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.
Furthermore, the lung cancer patients who had high expression of the PD-L1 biomarker were significantly more likely to respond to the atezolizumab treatment, with longer survival. Two-thirds of lung cancers in this trial expressed PDL-1 on either their cancer cells or immune cells, showing that the normal immune response had been activated.
“This study showcases a new approach to cancer therapy, which enhances the immune response to cancer and reduces the cancer’s ability to evade this natural immune response,” Fehrenbacher said.“It contributes to a growing body of evidence that biomarkers can help to identify the most effective treatments for cancer patients, moving oncology further down the path toward personalized, targeted medicine.”
Since Kaiser Permanente Oncology Clinical Trials began enrolling its first patients in clinical 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 into trials evaluating immune therapies for melanoma, a type of breast cancer, and bladder cancer, and has trials being activated for other cancer types.
Fehrenbacher and all study co-authors are members of the POPLAR 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.
