A short-lived IMPACT.

Top Line: Adjuvant chemo has long been the standard for resected stage II-III non-small cell lung cancer (NSCLC) until promising results with EGFR-inhibitors.

The Study: Initial successes came with erlotinib and gefitinib and then even more impressively when the third-generation osimertinib was given after adjuvant chemotherapy. The ADAURA trial investigated maintenance EGFR inhibition after chemotherapy, so how does targeted therapy alone fare against chemotherapy? The phase 3 Japanese IMPACT trial randomized 232 patients with resected stage II-III EGFR-mutant NSCLC to standard adjuvant chemo with cis/vinorelbine q3 weeks x 4 cycles versus gefitinib daily for two years. Just like in the Chinese ADJUVANT trial, adjuvant gefitinib monotherapy delayed recurrences by a median of 10 months, but in longer followup the Kaplan Meier curves for disease-free survival crossed and there was ultimately no significant difference in DFS (median 35.9 v 25.1 months). There was also no difference in overall survival at 5 years between arms (78% v 74.6%). While the outcomes were obviously similar between chemo alone and gefitinib alone, IMPACT wasn’t designed to demonstrate non-inferiority of EGFR inhibitor monotherapy.

TBL: Adjuvant chemo followed by maintenance osimertinib still reigns supreme for resected stage II-III EGFR-mutant NSCLC. | Tada, J Clin Oncol 2021