Randomized phase III trial comparing weekly docetaxel (D)-cisplatin (P) combination with triweekly D alone in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): An intergroup trial of JCOG0803/WJOG4307L.

Abstract

7509 Background: Tri-weekly D is one of the standard treatment regimens for elderly advanced NSCLC pts. To investigate whether the addition of a modified platinum agent might improve the survival in these patients, we conducted a phase III trial comparing weekly DP with tri-weekly D. Methods: Eligibility criteria were: chemotherapy-naïve; unfit for bolus P administration; stage III/IV or relapsed NSCLC; age≥70; PS 0-1. Pts were randomized to receive either DP or D by the minimization method, balancing for site, age (<75/≥75), and stage (III/IV). DP comprised administration of D (20 mg/m2) and P (25 mg/m2) iv on days 1, 8, and 15 every 4 weeks. D comprised administration of D (60 mg/m2) iv on day 1 every 3 weeks. The primary endpoint was overall survival (OS). The planned sample size was 190 pts in each arm, to provide an 80% power to detect a 0.752 hazard ratio for DP to D in regard to the OS, and a 5% one-sided alpha. Results: Between Oct 2008 and Sep 2010, 276 pts were randomized (D/DP: 137/139). The first planned interim analysis was performed on 221 assessable pts (D/DP: 108/113, <75/≥75: 22/78%, male/female: 70/30%, PS 0/1: 35/65%, III/IV or relapse: 32/68%). Information time, defined as the proportion of interim events to planned events, was 24% (=73/304). The median survival times of the DP and D groups were 13.3 and 17.3 months, respectively (hazard ratio [95% CI]: 1.557 [0.976-2.485]). The predictive probability that DP would be superior to D at the time of the final analysis was 0.996%, which led to early termination of the trial. The major grade 3-4 toxicities were (%D/DP): neutropenia 88/11%, anemia 3/16%, anorexia 1/10%, febrile neutropenia 17/0%, pneumonitis 3/2%. Treatment-related death occurred in 3 pts of the DP arm. The proportion of pts with an improved symptom score (FACT-L lung symptom subscale) after 3 courses of treatment was higher in the D arm. Conclusions: This study failed to demonstrate any advantage of the addition of weekly P to single-agent D in first line chemotherapy for elderly advanced NSCLC pts.