Immune Checkpoint Inhibition Efficacy May Vary by EGFR Allele in Lung Cancers

Although response to immune checkpoint inhibitors is generally low among patients with EGFR-mutant lung cancers, response to this therapy could vary by allele, a new study indicated.¹

In this retrospective study, Katherine Hastings, PhD, of Yale Cancer Center, and colleagues analyzed de-identified clinical and molecular data from 171 patients with EGFR-mutant lung cancer treated with immune checkpoint inhibitors at 4 major cancer centers in the United States. Due to a lack of tumor mutational burden in the first group of patients, additional data from 383 EGFR-mutant lung cancer cases was compiled to assess the relationship between tumor mutation burden and specific EGFR alterations.

The researchers found that patients with lung cancers with alterations in exon 19 of EGFR had worse outcomes when treated with PD-1/PD-L1 inhibitors compared with patients with EGFR wild-type cancers; however, patients with EGFR^L858R lung tumors had similar outcomes.

EGFR^T790M status and PD-L1 expression had no effect on response or survival outcomes after immune checkpoint blockade, the researchers wrote.

Overall, PD-L1 expression was similar across tumors with different EGFR alleles. Those tumors with EGFR alterations in exon 19 had a lower tumor mutation burden compared with EGFR^L858R tumors. Although there was an association between ever smoking status and higher tumor mutation burden, it was not highly evident when comparing only EGFR^L858R and EGFR with exon 19 alterations.

“These data serve as a foundation for further investigating which patients with EGFR-mutant disease have a higher likelihood of benefitting from immunotherapies, in particular when combined with chemotherapy or antiangiogenesis agents,” the researchers wrote.

In an editorial published with the study, Martin Fruh, of St. Gallen and University of Bern, and Solange Peters, of University Hospital of Lausanne, Switzerland, wrote, “Ongoing trials exploring the role of immune checkpoint inhibition in TKI-resistant EGFR mutated disease, including CheckMate 722 [ClinicalTrials.gov Identifier: NCT02864251], which [randomly assigns] patients to chemotherapy, chemotherapy plus nivolumab or ipilimumab/nivolumab; KEYNOTE 789 [ClinicalTrials.gov Identifier NCT03515837] (carboplatin/pemetrexed +/- pembrolizumab); and WJOG8515L (UMIN000021133) (nivolumab versus carboplatin/pemetrexed). Given the findings of Hastings et al, it will be of major interest to perform analyses of the different subtypes of EGFR mutations in addition to tumor mutation burden in these ongoing trials, as well as across available retrospective series.”²

References

Hastings K, Yu HA, Sanchez-Vega F, et al. EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer [published online May 14, 2019]. Ann Oncol. doi:10.1093/annonc/mdz141

Fruh M, Peters S. EGFR mutation subtype impacts efficacy of immune checkpoint inhibitors in non-small cell lung cancer [published online June 14, 2019]. Ann Oncol. doi:10.1093/annonc/mdz185