CISCA (cisplatin vs. carboplatin) meta-analysis: An individual patient data meta-analysis comparing cisplatin versus carboplatin-based chemotherapy in first-line treatment of advanced non-small cell lung cancer (NSCLC).

Background: The issue of the equivalence between carboplatin and cisplatin in the treatment of advanced NSCLC is still controversial. To answer this question, we conducted an individual patient (pt) data meta-analysis of randomized trials comparing cisplatin- and carboplatin-based chemotherapy (CT) in first-line treatment of advanced NSCLC. Methods: A literature search was performed to identify randomized trials investigating the substitution of carboplatin for cisplatin, combined with the same agent/s, in the first-line CT of advanced NSCLC. The primary end-point was overall survival (OS) and the secondary end-points were response rate (RR) and toxicity. For each end-point the analysis was based on a fixed-effects model. For the study of the effect on OS, Cox proportional hazards model was used. The probability to have an objective response or an adverse event was studied using a logistic regression model. Results: Nine trials were identified and the relative databases obtained. In total, 2,968 pts were randomized to receive CT with cisplatin (1,489) or with carboplatin (1,479), respectively. The RR was 30% and 24% for cisplatin- and carboplatin-based CT, respectively, with an OR of 1.37 (95% C.I.: 1.16–1.62; p < 0.001). Concerning the OS, carboplatin was associated with a relative risk of death 7% higher compared with cisplatin, even if this difference was not statistically significant (HR = 1.07; 95% C.I.: 0.99–1.15; p = 0.101). Patients on cisplatin-based CT had more nausea-vomiting and nephro-toxicity while thrombocytopenia was more frequent during carboplatin-based CT. Subgroup analyses revealed that cisplatin-based CT led to statistically significant advantage in survival in the subgroups of pts with non-squamous tumours and in those treated with third generation CT. Conclusions: CISCA is the first individual pt data meta-analysis on this subject. We found that cisplatin-based is superior to carboplatin-based CT in terms of RR; however, the increased RR does not translate into an OS benefit. Nevertheless, selected pts with advanced NSCLC may obtain slightly more benefit from cisplatin-based third generation CT. No significant financial relationships to disclose.