P2.01-102 Outcome of Patients with EGFR Exon 19 Mutation in a Phase III Randomized Trial Comparing Gefitinib to Gefitinib with Chemotherapy

Abstract

In patients with EGFR sensitizing mutations, the subtype of the EGFR mutation impacts the clinical outcome and carries both prognostic and predictive value. We had conducted a Phase III randomized trial in patients with advanced NSCLC harboring EGFR sensitizing mutation, ECOG PS 0 to 2 planned for first-line palliative therapy. The type of sensitizing EGFR mutation (exon 19 versus others) was a stratification factor. Randomization was 1:1 to gefitinib 250 mg orally daily (gef) or pemetrexed 500 mg/m2 and carboplatin AUC 5 IV 3-weekly for 4 cycles, followed by maintenance pemetrexed with gefitinib from day 1 (gef+C). The primary end-point was progression-free survival (PFS); secondary end-points included overall survival (OS), response rate and toxicity. We present the subset analysis of the patients with exon 19 in-frame deletion. Between 2016 and 2018, 216 patients with EGFR exon 19 mutation were randomly assigned to gef (n=109) and gef+C (n=107). The median age was 54 years, 51% were males, 20% were PS 2 and 21% had brain metastases. Median follow-up was 17 months (range, 7 to 30). Radiologic response rates were 81% and 75% in gef+C and gef arms respectively, P=0.29. Estimated median PFS was significantly longer with gef+C than gef [17 months, (95% CI, 12.4 to 21.6) versus 8 months (95% CI, 6.8 to 9.3); hazard ratio for disease progression or death, 0.49; 95% CI, 0.35 to 0.69; P<0.001]. Data for OS are immature. Clinically relevant ≥ grade 3 toxicities occurred in 55% and 23% of patients in gef+C and gef arms respectively, P<0.001. In patients with exon 19 in-frame deletion, combining pemetrexed and carboplatin chemotherapy with gefitinib led to a significant PFS prolongation, with an increase in clinically relevant severe toxicities.