Additional cisplatin/pemetrexed courses after initial EGFR TKI response improved progression-free but not overall survival compared with EGFR-TKI monotherapy.
EGFR tyrosine kinase inhibitors (TKIs) are standard first-line treatment options for advanced non-squamous NSCLC harboring an EGFR variant. Based on the results of FLAURA, third-generation EGFR TKI osimertinib is the first choice. However, acquired resistance to EGFR TKI limits the duration of response and survival.
Several studies have suggested the benefit of the concurrent combination of first-generation EGFR TKI and platinum doublet chemotherapy. The phase 3 AGAIN trial (JCOG1404/WJOG8214L) evaluated the effectiveness of adding three courses of chemotherapy to EGFR-TKI treatment for patients with stage IIIB/IV EGFR variant non-squamous NSCLC. Shintaro Kanda, MD, PhD, presented the results at the 2023 ASCO Annual Meeting, held June 2-6 in Chicago.
The participants were randomly assigned 1:1 to first-line treatment with EGFR TKI (gefitinib n=153; osimertinib n=97) until progression of disease (ie, standard arm), or EGFR TKI (gefitinib n=155; osimertinib n=96) from day 1 to day 56, followed by three courses of cisplatin/pemetrexed (on day 71, 92, and 113), followed by EGFR TKI until disease progression (ie, experimental arm). The primary endpoint of the study was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), overall response rate (ORR), and adverse events.
The median PFS was improved in the experimental arm: 18.0 versus 12.0 months (HR, 0.762; P=0.0058). In patients treated with gefitinib, mPFS was 14.4 versus 9.6 months (HR, 0.687; P=0.0015), and in patients treated with osimertinib, mPFS was 25.2 versus 20.4 months (HR, 0.812; P=0.2475), respectively. However, the PFS benefit was not translated into a benefit of median OS: 48.0 versus 48.0 months (HR, 0.985; P=0.4496), therefore, AGAIN did not reach its primary endpoint. ORR was 71.6% in the experimental arm compared with 78.0% in the standard arm. More patients in the experimental arm demonstrated adverse events compared with patients in the standard arm.
“The insertion of cisplatin/pemetrexed after the initial response to EGFR TKI improved progression-free but not overall survival compared with EGFR-TKI monotherapy,” concluded Dr. Kanda. “Mechanisms of acquired resistance are investigated using tumor tissue and liquid biopsy samples.”
Copyright ©2023 Medicom Medical Publishers
