Phase III multicenter web-based study demonstrating survival equivalents of nonplatinum-based chemotherapy for advanced non-small cell lung cancer (NSCLC): Subgroup analysis from D0112

Abstract

8100 Background: Based on limited data, NSCLC guidelines from ASCO includes non-platinum (non-P) therapy. D0112 provided the highest evidence supporting this guideline. Survival for this non-P and a carboplatin combination were equivalent. Recently, treatment choices and duration are based on subgroups of NSCLC. This report addresses the outcomes for subgroups from this trial. Methods: Eligibility patients (pts) with IIIB/IV NSCLC, performance status (PS) 0–2, and no prior chemotherapy. Randomized pts were stratified by stage (IIIB vs IV) and PS (0–1 vs 2) to arm A: carboplatin + docetaxel or arm B: gemcitabine + docetaxel. Therapy duration following 6 cycles was at the discretion of the investigator. Gender, histology, stage, PS, prior radiation, and central nervous system (CNS) metastasis were identified as independent variables. Multivariable analysis was performed using a proportional hazards regression. Wald test was performed. Treatment effect for each subgroups was evaluated. Results: Median follow-up time for 930 pts was 25.3 mos with 754 deaths. Median survival time (MST) for both treatment groups was 7.9 mos. Non-P arm was non-inferior to the platinum arm, unadjusted hazard ratio of 1.03 (95% confidence interval: 0.89 to 1.18) p = 0.017. By Wald tests, female (p = 0.002), IIIB (p = 0.025), adenocarcinoma (p = 0.002), and PS 0 (p < 0.001) had longer MST. Relative risk for each subgroups was not different for either treatment arm. Pts with non- squamous, no CNS disease and PS 0–1 had a MST of 9.5 mos. 314 pts (34%) received 6 cycles of therapy. Beyond 6 cycles, 163 pts received additional therapy and 151 pts had chemotherapy discontinued without disease progression. MSTs were 15.2 mos (1-yr 66%) and 13.1 mos (1-yr 55%) (p = 0.13), respectively. SAEs were more common for pts with more than 6 cycles (24% of pts) compared to treatment discontinued (16% of pts). Conclusions: For the palliative care of advanced NSCLC, non-P-based chemotherapy provides equivalent survival to carboplatin-based therapy. Females, intrathoracic disease, adenocarcinoma, and good PS do better with either therapy. This trial like others raises questions about the appropriate duration of therapy for incurable NSCLC. No significant financial relationships to disclose.