Comparison of Carboplatin With Cisplatin in Small Cell Lung Cancer in US Veterans

Abstract

Importance: The current standard of care for the treatment of small cell lung cancer (SCLC) is concurrent chemoradiation for patients with limited-stage SCLC (LS-SCLC) and chemoimmunotherapy for extensive-stage SCLC (ES-SCLC). The backbone of chemotherapy regimens in both is a platinum-etoposide doublet: cisplatin is traditionally the preferred platinum agent in the curative intent setting, whereas carboplatin is preferred in ES-SCLC because of its favorable toxicity profile.

Objective: To determine whether cisplatin is associated with better survival outcomes than carboplatin in treating LS-SCLC and ES-SCLC.

Design, setting, and participants: In this cohort study, data were compiled from the National Veterans Affairs Central Cancer Registry for patients with SCLC who received platinum-based multiagent chemotherapy between 2000 and 2020 for ES-SCLC and 2000 and 2021 for LS-SCLC. Only patients with pathologically confirmed cases of LS-SCLC who received concurrent chemoradiation and ES-SCLC who received chemotherapy were included.

Main outcomes and measures: The primary end point was overall survival (OS). The secondary end points included OS by Eastern Cooperative Oncology Group performance status, age, and laterality. Interval-censored Weibull and Cox proportional hazard regression models were used to estimate median OS and hazard ratios (HRs), respectively. Survival curves were compared by a Wald test.

Results: A total of 4408 SCLC cases were studied. Most patients were White (3589 patients [81.4%]), male (4252 [96.5%]), and non-Hispanic (4142 [94.0%]); 2262 patients (51.3%) were 60 to 69 years old, followed by 1476 patients (33.5%) aged 70 years or older, 631 patients (14.3%) aged 50 to 59 years, and 39 patients (0.9%) aged 30 to 49 years. Among 2652 patients with ES-SCLC, 2032 were treated with carboplatin-based therapy and 660 received cisplatin; the median OS was 8.45 months (95% CI, 7.75-9.20 months) for cisplatin and 8.51 months (95% CI, 8.07-8.97 months) for carboplatin (HR, 1.01; 95% CI, 0.91-1.12; P = .90). Subset analysis showed no survival difference between the 2 agents in different age or performance status groups except for patients aged 70 years and older, for whom the median OS was 6.36 months (95% CI, 5.31-7.56 months) for cisplatin and 8.47 months (95% CI, 7.79-9.19 months) for carboplatin (HR, 0.77; 95% CI, 0.61-0.96; P = .02). Multivariable analysis of performance status and age did not show a significant difference in survival between the 2 groups (HR, 0.96; 95% CI, 0.83-1.10; P = .54). Of 1756 patients with LS-SCLC, 801 received carboplatin, and 1018 received cisplatin. The median OS was 26.92 months (95% CI, 25.03-28.81 months) for cisplatin and 25.58 months (95% CI, 23.64-27.72 months) for carboplatin (HR, 1.04; 95% CI, 0.94-1.16; P = .46). The median OS was not significantly different between 2 agents according to cancer stage (I-III), performance status, and age groups. A multivariable analysis of factors associated with OS accounting for stage (I-III), performance status, and age did not demonstrate a significant difference in survival between carboplatin and cisplatin in patients with LS-SCLC (HR, 0.995; 95% CI, 0.86-1.15; P = .95).

Conclusions and relevance: Cisplatin is not associated with a survival advantage over carboplatin among patients with either ES-SCLC or LS-SCLC, irrespective of performance status and age. The favorable toxicity profile of carboplatin and comparable OS support its use in both LS-SCLC and ES-SCLC in clinical practice and may allow more room for combination with novel treatment strategies in clinical trials.

Figure 1.. Overall Survival for Patients With Extended-Stage Small Cell Lung Cancer Receiving Cisplatin and Carboplatin by Cancer Stage, Eastern Cooperative Oncology Group (ECOG) Performance Status, and Age

Graphs show overall survival for patients with cancer stage IV (A), by ECOG performance status (B-D), and by age group (E-G). The solid lines were estimated by a parametric Weibull proportional hazards regression analysis for interval censored data, and the dotted lines were generated by an interval-censored Cox proportional hazard model. HR indicates hazard ratio.

Figure 2.. Overall Survival for Patients With Limited-Stage Small Cell Lung Cancer Receiving Cisplatin and Carboplatin

The solid lines were estimated by a parametric Weibull proportional hazards regression analysis for interval censored data, and the dotted lines were generated by an interval-censored Cox proportional hazard model. HR indicates hazard ratio.

Figure 3.. Overall Survival for Patients With Limited-Stage Small Cell Lung Cancer Receiving Cisplatin and Carboplatin by Cancer Stage, Eastern Cooperative Oncology Group (ECOG) Performance Status, and Age

Graphs show overall survival by cancer stage (A-C), ECOG performance status (D-F), and age (G-I). The solid lines were estimated by a parametric Weibull proportional hazards regression analysis for interval censored data, and the dotted lines were generated by an interval-censored Cox proportional hazard model. HR indicates hazard ratio.