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ASCO 2021: EGFR- and MET-Based Biomarkers of Resistance to Therapy for Lung Cancer

By: Vanessa A. Carter, BS
Posted: Friday, June 25, 2021

Joshua Bauml, MD, of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and colleagues evaluated the efficacy of the monoclonal antibody amivantamab-vmjw plus the third-generation tyrosine kinase inhibitor lazertinib for the treatment of patients with osimertinib-relapsed, EGFR-mutant non–small cell lung cancer (NSCLC). At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, these investigators reported that the combination of these agents yielded responses in 36% of individuals who were chemotherapy-naive (Abstract 9006).

“Among these patients, genetic EGFR- and MET-based biomarkers of resistance identified a subgroup of patients more likely to respond to amivantamab and lazertinib, although additional patients lacking identified resistance markers also responded,” the study authors concluded. “An immunohistochemistry-based approach may identify patients most likely to benefit from the combination regimen, but further investigation is warranted.”

A total of 45 patients with EGFR exon 19 deletion or L858R mutation NSCLC who experienced disease progression on osimertinib were enrolled in this study; participants did not receive any previous chemotherapy. Circulating tumor DNA (ctDNA) and tumor biopsy specimens were collected before treatment, and individuals were administered 1,050/1,400 mg of amivantamab plus 240 mg of lazertinib.

A complete response was achieved by 1 patient, and 15 experienced a partial response. Additionally, 20 patients remain on treatment as of a median follow-up of 8.2 months, and 11 patients are continuing in response. Although the median duration of response was not reached, the median progression-free survival was 4.9 months.

Of the total participants, 44 were evaluable by ctDNA and 29 by tumor next-generation sequencing. These genetic tests identified 17 patients who were biomarker-positive, with just 8 responding; 8 of the 28 remaining patients also responded. Of 18 patients with unknown mechanisms of osimertinib resistance, 8 achieved a partial response, yet all 10 with non-EGFR/MET mechanisms of resistance did not respond. Biomarker-positive and remaining participants had median progression-free survival of 6.7 and 4.1 months, respectively.

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



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