Raising the Tail of the Survival Curve for Non-Small Cell Lung Cancer

Study shows long-term survival advantage with immunotherapy

Lung cancer cells

Patients with previously treated advanced non-small cell lung cancer (NSCLC) who received the anti–programmed cell death protein 1 (PD-1) antibody nivolumab achieved a greater duration of response compared with patients treated with docetaxel, indicating an improvement in long-term survival advantage up to and beyond a duration of four years, according to a Duke study published in The Lancet Oncology in October 2019.

Using pooled data from four clinical studies of nivolumab in 664 patients with previously treated NSCLC (CheckMate 017, 057, 063, and 003), the research team evaluated the long-term benefit of nivolumab and the effects of response and disease control on subsequent survival. Results showed that four-year overall survival with nivolumab was 14% for all patients, 19% for those with at least 1% PD-L1 expression, and 11% for those with less than 1% PD-L1 expression. Patients treated with nivolumab had a median overall survival of 10.3 months.

Scott J. Antonia, MD, PhD, director of the Duke Cancer Institute Center for Cancer Immunotherapy and lead author of the study, says the new findings indicate a shift in focus on the slope of the survival curve (median overall survival) to the tail of the curve (two- to five-year survival).

“We’re very enthusiastic about immunotherapy,” Antonia says. “We’ve known it improves median survival rates, but now we’ve shown it can result in better durable responses over the long term than chemotherapy. We’ve had an impact on the tail of the curve and are excited about moving this therapy to earlier-stage treatment settings.”

A number of studies have compared docetaxel with nivolumab in the second-line treatment setting, but this study is the first of its kind for two reasons. “This study is the first time we’ve had this many patients with this much long-term follow-up data. We’ve confirmed there can be a long-term benefit that we haven’t achieved to date without immunotherapy,” says Antonia.

Prior to the advent of immunotherapy as a second-line treatment for advanced NSCLC, the five-year survival rate of patients with metastatic lung cancer was about 5%. Because NSCLC accounts for approximately 85% of all lung cancers and is relatively insensitive to chemotherapy compared with small cell lung cancer, improving the efficacy of treatments and increasing survival rates continue to be the subject of many studies.

Antonia says the next step in immunotherapy research is studying combinations of immunotherapy agents plus chemotherapy. One upcoming Duke trial will combine the immune checkpoint inhibitors ipilimumab and nivolumab with various chemotherapy regimens. “The combination of these treatments in the first-line setting is looking promising, but these are still early days,” he says.