EGFR Inhibitor Mefatinib Under Study in Advanced EGFR-Mutant NSCLC
Posted: Thursday, April 8, 2021
Pingli Wang, MD, of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, and colleagues evaluated the resistance mechanism and efficacy of the EGFR inhibitor mefatinib in patients with EGFR-mutant non–small cell lung cancer (NSCLC). At the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer in Singapore (WCLC), held in virtual format in January 2021, the investigators reported objective response and disease control rates with this treatment (Abstract P76.28). In addition, they reported that circulating tumor DNA clearance at first follow-up may be linked to better outcomes.
In this phase II, open-label study, the researchers enrolled 71 patients with EGFR-mutant, stage IIIB to IV NSCLC. The median age of participants was 64, and they all had at least one measurable lesion, an Eastern Cooperative Oncology Group performance status of 0 to 3, a life expectancy of more than 3 months, and no previous exposure to EGFR tyrosine kinase inhibitors. Participants received 60 mg of mefatinib daily, and longitudinal plasma samples were obtained at baseline, every 6 weeks, and at progressive disease.
A total of 56 patients achieved partial response, and 13 achieved stable disease. As a result, the objective response rate was 81.2%, and the disease control rate was 100%. Due to lack of compliance, two patients were unable to be evaluated. Although the median overall survival for this cohort was not reached at data cutoff, the median progression-free survival was 15.5 months.
At the first follow-up, 71% of patients had no known mutations. The researchers discovered that individuals with a higher maximum allelic frequency or prior mutations in DNA damage repair were associated with a shorter progression-free survival, and 27 participants experienced progressive disease. The presence of EGFR T790M was noted in 48% of these patients, and resistance mechanisms such as ERBB2 amplification, MET amplification, and TP53_R209fs affected one patient each.
Disclosure: For full disclosures of the study authors, visit wclc.iaslc.org.