Immunotherapy for Lung Cancer May Increase Survival

Treatment with atezolizumab more than doubled survival compared with chemotherapy.

A phase 3 clinical trial found that the immunotherapy atezolizumab increased survival with less side effects compared with standard chemotherapy.

Included in the trial were 1225 patients with advanced non-small cell lung cancer who did not have any alternative treatment options. The investigators used an early analysis of the first 850 patients in the trial, according to a study published by The Lancet.

Patients either received treatment with atezolizumab, a programmed death ligand 1 (PD-L1) protein inhibitor, or with docetaxel chemotherapy.

Investigators discovered that patients in the atezolizumab treatment group survived for 13.8 months compared with 9.6 months in the chemotherapy group.

Atezolizumab was also associated with fewer side effects, with only 14.8% of patients experiencing grade 3 or 4 adverse events compared with 42.7% of patients administered chemotherapy, according to the study.

Despite a reduced occurrence of adverse events, 7.6% of patients discontinued treatment with atezolizumab. Approximately 18.7% of patients receiving chemotherapy treatment also discontinued due to adverse events.

"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. Recently, important advances in the treatment of the disease have come from immunotherapies that target the PD-L1 and PD-1 pathway," said lead author Achim Rittmeyer, MD. "Atezolizumab reinvigorates patients' immune systems against cancer, and our trial has shown that this has significant results for their survival."

The investigators also analyzed the levels of PD-L1 on the patients’ cancerous and immune cells, and survival. Patients with high levels of the protein benefitted the most from the drug, according to the study.

Patients with high PD-L1 expression survived for an average of 20.5 months on atezolizumab, while patients receiving chemotherapy only survived for an average of 8.9 months. Atezolizumab also increased survival in patients with low to no PD-L1 expression (12.6 months and 8.9 months, respectively).

"This is the first phase 3 trial of a PD-L1-directed immunotherapy in lung cancer,” said senior author David Gandara, MD. “The fact that it improves survival in patients with all categories of PD-L1 expression is highly encouraging and adds to the already known benefits of immunotherapy in lung cancer.”

Other immunotherapy drugs, such as nivolumab and pembrolizumab, inhibit PD-L1’s counterpart, the programmed cell death protein (PD-1). Typically, these proteins signal with each other to initiate an immune response, according to the study.

An excess of PD-L1 on cancer cell surfaces is thought to disguise them, and prevent immune cell response. By inhibiting the protein, atezolizumab could potentially make cancer cells become vulnerable to an immune attack.

The authors note that since it was an open-label study, the results may have been impacted. Additionally, 17% of patients in the chemotherapy group went on to take an immunotherapy drug after the study was finished, which could have increased survival among these patients.

This is the first phase 3 clinical trial of a PD-L1 inhibitor, and the results suggest the drug could offer patients with lung cancer an average of 4 months extended survival compared with chemotherapy, the study concluded.