Drawing on real world evidence and an exploratory analysis of four years of Flatiron Health clinical data, a team of Penn Medicine researchers led by first author Lova Sun, MD, has uncovered crucial insight regarding life-extending treatment for patients with non-small cell lung cancer (NSCLC), which has a five-year survival rate of 35%.

Immune checkpoint inhibition (ICI) therapy, a form of immunotherapy, has been standard front-line treatment for patients with NSCLC. The team looked into the impact of immunotherapy alone, chemotherapy alone, or the two in tandem for treating patients with NSCLC, with or without a genetic KRAS mutation.

Findings indicated that ICI alone prolonged overall survival (OS) for those with the KRAS variant, but that for those without the variant, their overall survival worsened with ICI alone.

However, when looking at ICI paired with chemotherapy, researchers did not observe significant differences for those with and without the KRAS mutation, demonstrating combination therapy’s benefits for those without the mutation.

“There will be clinical implications for a large portion of patients with advanced lung cancer, as we learn more about this mutation and how other mutations may play a role in response,” shared co-senior author Charu Aggarwal, MD, MPH In a Penn Medicine news release. Lova Sun, MD, added, “KRAS is the most common alteration in non-small cell lung cancer, and we hope this and future studies can inform optimal treatment selection in advanced lung cancer.”

PC3I Innovation Faculty Ronac Mamtani, MD, MSCE, and co-senior author explained, “This is a prime example of how real-world data can complement clinical trial data to help inform decision making between patients and their oncologists.”

The study, “Association Between KRAS Variant Status and Outcomes With First-line Immune Checkpoint Inhibitor–Based Therapy in Patients With Advanced Non–Small-Cell Lung Cancer,” was published in JAMA Oncology on April 15, 2021. In addition to first author Lova Sun, MD and co-senior authors Ronac Mamtani, MD, MSCE and Charu Aggarwal, MD, MPH, the other authors were Miles Hsu, MD; Roger B. Cohen, MD; and Corey J. Langer, MD.  The study has received press coverage from ASCO Post, Healio, and Medicine Matters oncology.