Abstract
Carboplatin remains the backbone for combination therapy of patients with many cancers including NSCLC. Dosing ranges from AUC 5-7.5, but the optimal AUC dosing of carboplatin is unclear. Doses of AUC equal to 5 or 6 are commonly administered in NSCLC based on sentinel studies leading to the approval of carboplatin-based regimens. Therefore, we sought to evaluate if there is a difference in efficacy and/or toxicity between the two doses. We conducted a single-institution retrospective analysis of patients with advanced NSCLC who were treated with carboplatin/pemetrexed from 2011-2016. During this period, an institutional chemotherapy template adjustment from AUC 5 to 6 occurred with change in electronic medical record in 2014. In addition, the advent of commercial PD-1 therapy occurred in October 2015. Patients were divided into two groups based on treatment dose received: Carboplatin AUC 5 and Carboplatin AUC 6. Progression Free Survival (PFS) and Overall Survival (OS) were calculated using the Kaplan-Meier method and Cox proportional hazards [PH] models adjusted for confounding factors. Grade 3/4 events, dose reductions, and likelihood to receive 2nd line or greater immunotherapy or targeted therapy were examined using logistic regression. A total of 133 patients were analyzed, with 59 (44%) treated with Carboplatin AUC 5 and 74 (56%) with Carboplatin AUC 6. Most patients treated with AUC 5 were treated prior to 2014 (83.4%) and the majority of patients treated with AUC 6 were treated in 2014 or later (96%). PFS was similar between both groups (HR = 0.99, CI 0.68-1.43, p = 0.548), but AUC 6 was associated with significantly superior OS (HR = 0.67, CI 0.46-0.99, p=0.045). Treatment with AUC 6 was more likely to lead to dose reduction (OR = 3.6, CI 1.11-10.17, p=0.032) and a trend towards more Grade 3/4 adverse events in the AUC 6 group was observed (OR = 2.43, CI 0.78-7.52, p=0.124). Patients in the AUC 6 group were more likely to receive 2nd line or greater immunotherapy (OR= 3.73, CI 1.35-10.26, p=0.011). Patients treated with Carboplatin AUC 6 had better OS as compared to AUC 5. However, they were also more likely to receive post-platinum immunotherapy, which may explain their survival advantage. In this real-world analysis of Carboplatin AUC 5 vs 6, there appears to be no clinically significant difference in survival and toxicity outcomes between the two dosing strategies in patients with advanced NSCLC.
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