Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study
Mené sur 165 patients chinois atteints d'un cancer avancé du poumon non à petites cellules présentant des mutations EGFR, cet essai de phase III compare l'erlotnib à une chimiothérapie combinant gemcitabine et carboplatine en traitement de première ligne
Activating mutations inEGFRare important markers of response to tyrosine kinase inhibitor (TKI) therapy in non-small-cell lung cancer (NSCLC). The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus standard chemotherapy in the first-line treatment of patients with advancedEGFRmutation-positive NSCLC. We undertook an open-label, randomised, phase 3 trial at 22 centres in China. Patients older than 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation ofEGFR(exon 19 deletion or exon 21 L858R point mutation) received either oral erlotinib (150 mg/day) until disease progression or unacceptable toxic effects, or up to four cycles of gemcitabine plus carboplatin. Patients were randomly assigned (1:1) with a minimisation procedure and were stratified according toEGFRmutation type, histological subtype (adenocarcinomavsnon-adenocarcinoma), and smoking status. The primary outcome was progression-free survival, analysed in patients with confirmed disease who received at least one dose of study treatment. The trial is registered atClinicalTrials.gov, numberNCT00874419, and has completed enrolment; patients are still in follow-up. 83 patients were randomly assigned to receive erlotinib and 82 to receive gemcitabine plus carboplatin; 82 in the erlotinib group and 72 in the chemotherapy group were included in analysis of the primary endpoint. Median progression-free survival was significantly longer in erlotinib-treated patients than in those on chemotherapy (13.1 [95% CI 10.58?16.53]vs4.6 [4.21?5.42] months; hazard ratio 0.16, 95% CI 0.10?0.26; p<0.0001). Chemotherapy was associated with more grade 3 or 4 toxic effects than was erlotinib (including neutropenia in 30 [42%] of 72 patients and thrombocytopenia in 29 [40%] patients on chemotherapyvsno patients with either event on erlotinib); the most common grade 3 or 4 toxic effects with erlotinib were increased alanine aminotransferase concentrations (three [4%] of 83 patients) and skin rash (two [2%] patients). Chemotherapy was also associated with increased treatment-related serious adverse events (ten [14%] of 72 patients [decreased platelet count, n=8; decreased neutrophil count, n=1; hepatic dysfunction, n=1]vstwo [2%] of 83 patients [both hepatic dysfunction]). Compared with standard chemotherapy, erlotinib conferred a significant progression-free survival benefit in patients with advancedEGFRmutation-positive NSCLC and was associated with more favourable tolerability. These findings suggest that erlotinib is important for first-line treatment of patients with advancedEGFRmutation-positive NSCLC. F Hoffmann-La Roche Ltd (China); Science and Technology Commission of Shanghai Municipality.