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Response to Immunotherapy in NSCLC: Beyond EGFR Mutations

By: Vanessa A. Carter, BS
Posted: Friday, February 4, 2022

Karan Seegobin, MD, of the Mayo Clinic, Jacksonville, Florida, and colleagues reviewed published data on immune checkpoint inhibitor (ICI) therapy in non–small cell lung cancer (NSCLC) with genetic mutations. These investigators concluded that immunotherapy after disease progression on targeted agents may be considered as a treatment option, subject to physician and patient discretion. The results of this study were published in Frontiers in Oncology.

“We see low responses to ICI in ALK- and RET-altered NSCLCs, whereas BRAF, KRAS, and c-MET alterations were associated with benefit from ICIs, and PD-L1 positive KRAS-mutant NSCLCs may be more responsive to ICI monotherapy,” the investigators commented. “Furthermore, the response to ICIs in KRAS-mutant NSCLCs may vary depending on coexisting mutations, and responses to ICIs in HER-2, ROS1-, and NTRK-altered NSCLCs are less clear and vary significantly across a small number of studies.”

The data on patients with NSCLC-harboring mutations in genes ALK, ROS1, BRAF, c-MET, RET, NTRK, KRAS, and HER2 were retrospectively reviewed.

Objective response rates associated with ICI treatment in NSCLC-harboring BRAF (0%–54%), c-MET (12%–49%), and KRAS (18.7%–66.7%) mutations were comparable to those in nonmutant NSCLC. Objective response rates among patients with RET (< 10%) and ALK (0%) mutations were low, and rates among those with ROS1 fusion (0%–17%), NTRK fusion (50%), and HER2 (7%–23%) mutations varied greatly.

There also appeared to be no significant correlation between treatment outcome and tumor mutation burden or PD-L1 expression. Unfortunately, the investigators noted, the process of selecting patients with NSCLCs harboring mutations who will benefit from immunotherapy is still unknown. 

Disclosure: The study authors reported no conflicts of interest.


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