Age, Sex, Genomic Profiles Matter: Choosing Immunotherapies for Younger Patients With NSCLC

By: Celeste L. Dixon
Posted: Thursday, September 19, 2024

New study results reiterate the importance of comprehensive genomic and immune profiling in patients with non–small lung cancer (NSCLC) who are younger than age 65. Such profiling helps to find the most precise targeted therapies or immunotherapies possible, wrote Shakti H. Ramkissoon, MD, of Wake Forest School of Medicine, Winston-Salem, North Carolina, and colleagues in Frontiers in Immunology.

Although Medicare typically covers comprehensive genomic and immune profiling for patients aged 65 and older, commercial insurance plans often do not cover it for younger patients. Such cost-based roadblocks are regrettable, the authors declared, calling comprehensive genomic and immune profiling the cornerstone of personalized medicine.

The investigators’ retrospective analysis included 8,230 patients with NSCLC, divided among those aged 65 and older (n = 6,119; mean age, 75 years) and younger than 65 (n = 2,111; mean age, 58 years). They used a 5-year sliding threshold for those younger than 45 to younger than 65 to define various groups of younger patients’ genomic alterations and immunogenic markers; they also considered differences between male and female patients.

Specifically, Dr. Ramkissoon and co-researchers reported the following findings:

Younger patients’ tumors—especially those in men—tend to be enriched in clinically relevant genomic alterations including EGFR, ALK, ROS1, and NTRK1, and to have gene-expression patterns indicative of reduced immune system activation.
Younger male patients receiving immunotherapy alone—a current mainstay of NSCLC treatment—had significantly worse survival than older male patients. However, adding chemotherapy seemed to reduce this disparity. The presence of oncogenic driver alterations and biomarkers for response to immunotherapy must be verified prior to initiating treatment, the authors argued, because “patients with oncogenic driver alterations and less immunogenic tumors derive minimal therapeutic benefit from immunotherapy...,” the team wrote.
On the other hand, younger female patients had significantly better survival than older females (≥ age 65) when treated with immunotherapy plus chemotherapy, whereas treatment solely with immunotherapy yielded similar outcomes.

Disclosure: For full disclosures of the study authors, visit frontiersin.org.

Frontiers in Immunology