How Immunotherapy Is Dramatically Changing Treatment for Non-Small and Small Cell Lung Cancer

Image: ranjith ravindran/Shutterstock

The recently concluded 19th World Congress on Lung Cancer featured a number of practice-changing scientific advances for patients with lung cancer. These advances span from the topic of early detection to treatment of advanced-stage lung cancer. Early detection of lung cancer has been shown in the National Lung Cancer Screening Study to reduce lung cancer-related and overall mortality by 20% and 6% respectively. The results of the NELSON Study, reported at the World conference, further confirmed the role of CT scans for early detection of lung cancer. The NELSON Study randomized approximately 16,000 high-risk individuals to CT screening or no screening. For patients in the screened arm, annual CT scans were performed on years 1 and 2, 4 , and 6.5. 2.2% of the patients had a positive screen, out of which lung cancer was detected in 0.9%. By year 10 there was a reduction in lung cancer-related mortality of 26% in males and 39% in women. These overall results were even more favorable than what was observed in the NLST trial. Among patients diagnosed with screening-detected lung cancer, a higher proportion had stage 1 disease, compared to patients in the control group. These results provide further evidence that CT screening should be performed on patients with a high risk between 55 and 75 years of age with a history of smoking for early detection of lung cancer.

Another major advance involved improved survival outcomes for patients with surgically unresectable stage 3 disease. The PACIFIC trial randomized patients with stage 3, surgically unresectable, locally advanced non-small cell lung cancer (NSCLC) to chemoradiotherapy followed by Durvalumab, a PD-L1 inhibitor, or placebo upon completion of chemoradiotherapy. The hazard ratio for progression-free-survival was 0.52; for overall survival, the hazard ratio was 0.68 favoring the use of Durvalumab. This is the first trial to show improved overall survival for patients with stage 3 non-small cell lung cancer in nearly two decades. Duvalumab has already received approval by the United States FDA for treatment in this setting. These results will lead to greater adoption of immune checkpoint inhibition in patients with stage 3 non-small cell lung cancer.

Another important study reported at this meeting involved integration of immune checkpoint inhibition for patients with small cell lung cancer. For nearly three decades, platinum-based chemotherapy has remained the standard of care for patients with extensive stage small cell lung cancer. At the world conference, Dr. Liu and colleagues reported the results of a phase 3 clinical trial that evaluated the addition of atezolizumab, an immune checkpoint inhibitor, to standard platinum-based chemotherapy. 400 patients were randomized 1:1 to chemotherapy with atezolizumab or chemotherapy plus placebo. The study demonstrated a significant improvement in overall survival with a hazard ratio of 0.7. The median overall survival was 10.3 months for the control group and 12.3 months for the experimental group. The hazard ratio for progression-free-survival was 0.77. The combination treatment was tolerated well overall and the treatment benefit appeared to be distributed across all subgroups of patients evaluated in the trial. Based on these results, it is likely that atezolizumab will soon be available for clinical use for patients with extensive stage small cell lung cancer.

Integration of immunotherapy has made a dramatic change in the treatment landscape for non-small cell lung cancer and small cell lung cancer in a short time. Immune checkpoint inhibitors are being evaluated in earlier stages of the disease. The use of predictive biomarkers to select patients has helped deliver individualized therapy to patients with lung cancer. Taken together, these developments mark another major step forward in improving outcomes for lung cancer.

Disclosures: Dr. Ramalingam has served on advisory board meeting/consultation and has received honorarium from Abbive, Astra Zeneca, Bristol Myers Squibb, Genentech, Roche, Lilly, Loxo, Tesaro and Nektar.

More from Op-Med