A Randomized Phase 2 Study of Gefitinib With or Without Pemetrexed as First-line Treatment in Nonsquamous NSCLC With EGFR Mutation: Final Overall Survival and Biomarker Analysis
Journal
Journal of Thoracic Oncology
Journal Volume
15
Journal Issue
1
Pages
91-100
Date Issued
2020
Author(s)
Cheng Y.
Murakami H.
He J.
Nakagawa K.
Kang J.H.
Kim J.-H.
Hozak R.R.
Nguyen T.S.
Zhang W.L.
Enatsu S.
Puri T.
Orlando M.
Abstract
Introduction: Clinical studies have shown that a combination of a tyrosine kinase inhibitor (TKI) and pemetrexed overcame acquired resistance to epidermal growth factor receptor (EGFR) TKI in NSCLC. Previously, pemetrexed+gefintib (P+G) had improved progression-free survival (PFS) compared with gefitinib. We present OS, updated PFS, biomarker analysis, and safety of P+G versus gefitinib. Methods: This was a phase 2, multicenter, randomized study conducted in East Asian patients with advanced nonsquamous NSCLC with EGFR mutations. Patients were randomized (2:1) to receive P+G (500 mg/m2 intravenously 3-weekly + 250 mg/day orally) or gefitinib. Results: In total, 191 patients (P+G, n=126; gefitinib, n=65) comprised the intent-to-treat and safety populations. Median OS was 43.4 months in P+G versus 36.8 months in gefitinib arm; adjusted HR 0.77 (95% CI, 0.5-1.2); one-sided P=0.105. Median PFS was significantly longer in the P+G (16.2 months) versus gefitinib arm (11.1 months); adjusted HR 0.67 (95% CI, 0.5-0.9); one-sided P=0.009. In the P+G and gefitinib arms, median PFS was 22.6 and 11.0 months, respectively, in patients with low thymidylate synthase (TS) expression, and 12.6 and 9.9 months, respectively, in patients with high TS expression. Common second-line post-discontinuation systemic therapies were EGFR-TKIs and chemotherapy. Most patients experienced at least one adverse event. Conclusions: Addition of pemetrexed to EGFR TKI gefitinib resulted in significantly improved PFS and numerically longer OS compared with gefitinib in treatment-na?ve patients with EGFR-mutated advanced nonsquamous NSCLC. Low TS expression appeared to be a good predictor for treatment outcomes. ? 2019 International Association for the Study of Lung Cancer
SDGs
Other Subjects
afatinib; alanine aminotransferase; aspartate aminotransferase; crizotinib; cyanocobalamin; dexamethasone; epidermal growth factor receptor; erlotinib; folic acid; gefitinib; gilteritinib; icotinib; nazartinib; osimertinib; pemetrexed; protein tyrosine kinase inhibitor; rociletinib; thymidylate synthase; tumor marker; antineoplastic agent; biological marker; EGFR protein, human; epidermal growth factor receptor; gefitinib; pemetrexed; protein kinase inhibitor; quinazoline derivative; acne; adult; advanced cancer; aged; anemia; anorexia; Article; cancer combination chemotherapy; cancer survival; clinical outcome; controlled study; diarrhea; drug safety; drug withdrawal; dry skin; dysgeusia; East Asian; edema; EGFR gene; fatigue; female; gene mutation; human; hyperpigmentation; leukocyte count; maculopapular rash; major clinical study; male; monotherapy; multicenter study; multiple cycle treatment; nausea; neutrophil count; non small cell lung cancer; open study; oral mucositis; outcome assessment; overall survival; paronychia; peripheral edema; phase 2 clinical trial; priority journal; protein expression; pruritus; randomized controlled trial; rash; side effect; survival rate; survival time; treatment response; vomiting; clinical trial; genetics; lung tumor; mutation; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; ErbB Receptors; Gefitinib; Humans; Lung Neoplasms; Mutation; Pemetrexed; Protein Kinase Inhibitors; Quinazolines
Publisher
Elsevier Inc
Type
journal article