Immune checkpoint blockade
Historically, EGFR-mutated NSCLCs have not derived comparable benefit to EGFR-wild type (WT) tumors from checkpoint inhibitors. For that reason, in EGFR-mutated tumors, guidelines from the National Comprehensive Cancer Network (NCCN) suggest immune-targeted treatment should be used only on clinical trials or after receipt of EGFR-targeted tyrosine kinase inhibitors and cytotoxic chemotherapy. Several recent studies (IMpower and ATLANTIC), however, have suggested that selected EGFR-mutated patients can benefit from immune-targeted treatment.
Katherine Hastings, PhD, of Yale University, New Haven, Conn., and associates found, in a multi-institution clinical-molecular data review, that among the 44 of 171 EGFR-mutated tumors with L858R mutations, benefit from checkpoint inhibitors was comparable to WT tumors with regard to overall response rate and OS, but not PFS. Additionally, tumors with the EGFR T790M mutation demonstrated similar benefit from checkpoint inhibitors as in WT tumors, L858R-mutated tumors (but not exon 19 deleted tumors) had high tumor mutation burden, and PD-L1 expression did not influence outcome from immunotherapy.
What this means in practice
I agree with the modesty of the authors’ conclusion that these findings should not change clinical practice but rather should encourage further research into which patients with EGFR-mutant disease might benefit from immune-targeted therapy. For now, outside of a clinical trial, in EGFR-mutated patients, I will follow NCCN guidelines, using immune-targeted therapy off-study only with attentiveness to the particular immunotherapy regimens that have shown promise in the literature – and later, not earlier.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.