Randomized Phase III Study of EGFR Tyrosine Kinase Inhibitor and Intercalated Platinum-doublet Chemotherapy for Non-small Cell Lung Cancer Harboring EGFR Mutation
Mené sur 503 patients atteints d'un cancer du poumon non à petites cellules avec mutation EGFR et de stade avancé, cet essai multicentrique de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'ajout d'un doublet de chimiothérapie (cisplatine et pémétrexed) à un inhibiteur de tyrosine kinase de l'EGFR en monothérapie de première ligne (géfitinib ou osimertinib)
Purpose: This study was performed to confirm the superiority in overall survival (OS) of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) (gefitinib or osimertinib) monotherapy versus EGFR-TKI with intercalation of cisplatin plus pemetrexed as the first-line treatment for patients with advanced non-squamous non-small cell lung cancer (NSqNSCLC) harboring EGFR mutation.
Patients and Methods: This was an open-label, multicenter, randomized phase III study. Patients with chemotherapy-naïve advanced or recurrent NSqNSCLC harboring EGFR mutation (exon 19 deletion or exon 21 L858R point mutation) were randomly assigned (1:1) to EGFR-TKI monotherapy or EGFR-TKI plus intercalated chemotherapy group. The primary endpoint was OS, and the secondary endpoints included progression-free survival (PFS).
Results: From December 2015 to October 2020, 501 patients were randomized. The EGFR-TKI was changed from gefitinib to osimertinib in October 2018 (gefitinib cohort: n=308, osimertinib cohort: n=193). There was no survival advantage in the EGFR-TKI plus intercalated chemotherapy group; the median survival time of both groups was 48.0 months (hazard ratio, 0.985; 91.4% confidence interval, 0.796–1.219; one-sided P=0.4496). The median PFS time was 12.0 months in the EGFR-TKI monotherapy group and 18.0 months in the EGFR-TKI plus intercalated chemotherapy group (hazard ratio, 0.762; 95% confidence interval, 0.628–0.925; one-sided P=0.003). The OS and PFS trends in both gefitinib and osimertinib cohorts were identical to those in the entire population.
Conclusions: The intercalation of cisplatin plus pemetrexed after the response to EGFR-TKI improved PFS but not OS compared with EGFR-TKI monotherapy as the first-line treatment for advanced NSqNSCLC harboring EGFR mutation.