CDDP-based doublet chemotherapy provides a significant but modest survival prolongation in untreated advanced NSCLC with MST of around 12 months. Based on the favorable efficacy profile in our previous phase II trial of triplet chemotherapy with CDDP, DOC, and CPT (response rate: 57.1%, MST: 17 months) (JTO 2007), we conducted a phase III study to compare this regimen with CDDP and DOC doublet therapy in the first-line setting.Methods
Patients were randomly allocated to the triplet therapy (A arm; CDDP 60 mg/m2, day 1; DOC 60 mg/m2, day 1; and CPT 60 mg/m2, day 2; q3wks, determined based on our phase I study result) or a standard doublet chemotherapy (B arm; CDDP 80 mg/m2, and DOC 60 mg/m2, day 1; q3 wks). The primary end point was OS whereas secondary end points included response rates, PFS, and toxicity.Results
Between 2004 and 2009, 120 patients were enrolled (A/B: 60 patients each). Objective response was comparable between the arms (18 patients [30%] each, P = 0.571). As for toxicity, grade 3–4 neutropenia, principal toxicity, was observed in 93% versus 58% (P < 0.001). Although grade 3 febrile neutropenia was observed in 53% and 18% of the patients (P < 0.001), none of whom further developed toxic deaths. At a median follow-up time of 64.2 months, median PFS time and 1-year PFS rate were 5.3 versus 4.3 months and 13.3% versus 11.7%, respectively (stratified logrank test; P = 0.872). There was also no difference in OS (MST, 16.8 versus 12.2 months; 1-year OS rate, 68.0% versus 53.0%; stratified logrank test; P = 0.846). Subgroup analysis for OS showed that never smokers (HR = 0.366; 95% CI = 0.072–1.866) tended to benefit from the triplet chemotherapy compared with ever-smokers (HR = 1.380; 95% CI = 0.771–2.473) despite no statistical significance (P-value for interaction = 0.150). Similar trend in interaction between treatment effect and smoking status was also observed in PFS.Conclusions
This triplet chemotherapy failed to produce a significant antitumor activity when compared with the standard doublet therapy.