Pemetrexed versus gefitinib as a second-line treatment in advanced non-squamous non-small-cell lung cancer patients harbouring wild-type EGFR (CTONG0806): a multicenter randomized trial
Mené sur 157 patients atteints d'un cancer avancé non épidermoïde du poumon non à petites cellules sans mutation EGFR, cet essai randomisé compare l'efficacité, du point de vue de la survie sans progression, et la toxicité du pemetrexed et du gefitinib en traitement de deuxième ligne
Background : CTONG0806 assessed the efficacy of pemetrexed versus gefitinib as second-line treatment in advanced non-squamous non-small-cell lung cancer (NSCLC) harbouring wild-type epidermal-growth-factor receptor (EGFR). Patients and methods : Patients with locally advanced or metastatic non-squamous NSCLC harbouring wild-type EGFR, detected by direct sequencing, and previously treated with platinum-based chemotherapy were randomized to receive gefitinib (250 mg/day) orally or pemetrexed (500 mg/m2) intravenously on day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). The Independent Review Committee (IRC) evaluated all pictorial data. Results : From February 2009 to August 2012, 161 patients were enrolled, and 157 were evaluable (81 in the gefitinib arm, 76 in the pemetrexed arm). Baseline characteristics were balanced between the two arms. The median PFSs were 4.8 versus 1.6 months in the pemetrexed and gefitinib arms, respectively (HR 0.54, 95% CI 0.40-0.75, P<0.001) as confirmed by IRC evaluation (5.6 vs. 1.7 months, HR 0.53, 95% CI 0.38-0.75, P<0.001). The median overall survival (OS) showed a trend of superiority in the pemetrexed arm (12.4 vs. 9.6 months, HR 0.72, 95% CI 0.49-1.04, P=0.077). Quality-of-life assessment showed no marked difference between the arms. No unexpected adverse events were found. Of 108 patients with sufficient DNA samples, EGFR mutation status was re-tested by Scorpion amplification refractory mutation system (ARMS); 32 (29.6%) tested positive (19 in the pemetrexed arm, 13 in the gefitinib arm; median PFS: 8.1 vs. 7.0 months, HR 0.94, 95% CI: 0.43-2.08, P=0.877). Conclusions : CTONG0806 is the first trial to show significant improvement in PFS and an improved OS trend with pemetrexed compared with gefitinib as second-line setting treatment for EGFR wild-type advanced non-squamous NSCLC. ARMS is superior to direct sequencing in excluding false-negative patients.