Phase III randomized controlled trial of gefitinib versus chemotherapy in EGFR-positive treatment-naïve metastatic lung cancer: Long-term outcome after eight years

• DOI: 10.4103/crst.crst_307_23
• Publication Date: 2024-03-24T19:00:20Z
• Authors: Ajaykumar Singh; Vijay Patil; Nandini Menon; Sucheta More; Srushti Jain; Supriya Goud; Darshit Shah; Minit Shah; Kunal Jobanputra; Ahmad Ubharay
• Keywords: long-term outcome; egfr mutation; 03 medical and health sciences; 0302 clinical medicine; non-small-cell lung cancer; gefitinib; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; first-line treatment; RC254-282

Background: This was the first Phase III randomized study comparing an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), gefitinib, to standard-of-care chemotherapy (pemetrexed + carboplatin followed by pemetrexed maintenance) in advanced EGFR- mutated lung cancer. The initial interim analysis showed superiority of gefitinib over terms progression-free survival (PFS), objective response rate (ORR), and safety. Objectives: We aimed evaluate long-term outcomes. Our primary endpoint overall (OS) secondary endpoints were 2 (PFS2) duration (DOR). Materials Methods: a open-label, randomized, parallel-group conducted Department Medical Oncology, Tata Memorial Hospital, Mumbai, India, patients with EGFR mutation-positive treatment-naïve Stage IIIB or IV adenocarcinoma. Patients (250 mg orally daily) (area under curve 5) (500 mg/m ) chemotherapy, maintenance ). Results: Between February 2012 April 2016, 290 randomized:145 each arm. At median follow-up 104 months, all (100%) had progressed, 287 (99%) deaths occurred. OS arm 19.5 months (95% confidence interval [CI], 16.7-24.8) compared 22.6 CI, 19.2-25.2) arm; hazard ratio [HR], 1.11; 95% 0.87-1.39; P, 0.423. PFS2 15.5 13.5-18.1) 12.5 11.1-14.5) HR, 0.86 0.66-1.13); 0.270. DOR improved (7.6 months; 5.45-9.88) 3.9 3.49-6.35) 0.59; 0.42-0.82; 0.002. 5-year 4.1% versus 6.8% Conclusions: establishes advantages first-line TKI therapy durable numerically superior PFS2. Due crossover post-progression, there is no significant difference (Clinical Trials Registry India number: CTRI/2015/08/006113).