A large trial by UC Davis professor David Gandara has found that the immunotherapy atezolizumab was superior to chemotherapy for patients with advanced non-small-cell lung cancer.
The research, published today in The Lancet, found that patients survived longer with fewer side effects on atezolizumab compared to chemotherapy, the standard treatment. Atezolizumab is an immunotherapy that blocks the PD-L1 protein, a lung cancer biomarker present to some degree in 70 percent of lung cancer patients.
The phase 3 clinical trial enrolled 1,225 patients with advanced non-small-cell lung cancer who had failed other treatment options. The study used an early analysis of the first 850 patients, half of whom were given atezolizumab and half of whom received docetaxel chemotherapy.
“The most important result is that atezolizumab showed benefit in all categories of patients,” said Gandara, director of thoracic oncology and senior advisor for experimental therapeutics at the UC Davis Comprehensive Cancer Center, and the study’s senior author.
Gandara said the drug worked best for patients with the highest levels of the PD-L1 protein on their cells – more than doubling survival compared with those given chemotherapy – but still increased survival by three and a half months for those with little to no levels of the protein.
“These results, together with those shown in other recent trials, bring new hope for all patients with advanced non-small-cell lung cancer,” he said.
Atezolizumab also had fewer side effects than chemotherapy with about 15 percent of those given the immunotherapy drug having moderate to severe side effects compared with over 40 percent of those given chemotherapy.
Other immunotherapies for non-small-cell lung cancer, such as nivolumab and pembrolizumab, are designed to block PD-L1’s counterpart, the programmed cell death protein 1 (PD-1) which is located on the immune cell surface. Normally the PD-L1 and PD-1 proteins signal to one another to activate the immune system to attack tumors.
It’s thought that the extra PD-L1 protein on some cancer cells’ surfaces helps them hide from the immune system, meaning it cannot find and kill cancer cells as usual. But by blocking the extra PD-L1 protein, atezolizumab may unveil the cells to the immune system so they can be attacked and destroyed. The study is the first phase 3 trial of a PD-L1 inhibitor drug and has shown longer survival than trials of PD-1 inhibitors.
“Lung cancer is the most common cancer affecting 1.8 million people each year worldwide. It is also the leading cause of cancer death worldwide and survival remains stubbornly low,” said Achim Rittmeyer of the University Goettingen, Germany and the study’s lead author. “Atezolizumab reinvigorates patients’ immune systems against cancer, and our trial has shown that this has significant results for their survival.”
The study was funded by F. Hoffman-La Roche Ltd and Genentech Ltd. Other institutions involved in the research included Lungenfachklinik Immenhausen, Aix Marseille Universite, Sungkyunkwan University School of Medicine, Seconda Università degli Studi di Napoli, Asklepios Fachkliniken München-Gauting, Karmanos Cancer Institute/Wayne State University, Aichi Cancer Center Hospital, Institute M. Sklodowska-Curie, Hospital Regional Universitario Carlos Haya, AOU San Gerardo, Minnesota Oncology, Southern California Permanente Medical Group, PUCRS School of Medicine, University of California, Centro Internacional de Estudios Clinicos, European Institute of Oncology, Istanbul University Cerrahpasa Medical Faculty Hospital, Seoul National University Bundang Hospital and Genentech Inc.