Carboplatin Should Be Favored Over Cisplatin for Small Cell Lung Cancer Treatment Due to Toxicity Profile

In a multivariable analysis, treatment with carboplatin is favored for extensive-stage cell lung cancer, even if it is not found to increase overall survival compared to standard care.

In patients with small cell lung cancer (SCLC), platinum agents cisplatin (Platinol; Bristol-Myers Squibb Company) and carboplatin (Paraplatin; Bristol-Myers Squibb Company) were not associated with significant differences in overall survival (OS), according to authors of a study published in Jama Network Open. Further, the median OS was not significantly different when accounting for cancer stages 1 to 3, patient age, or performance status.

“These findings suggest that cisplatin is not associated with a survival advantage over carboplatin in either extensive-stage SCLC (ES-SCLC) or limited-stage SCLC (LS-SCLC), but carboplatin use should be favored because of its favorable toxicity profile,” wrote the study authors.

SCLC is a type of lung cancer that nearly always affects cigarette smokers. It leads to rapid, early, and widespread metastases, and it accounts for approximately 14% of pulmonary malignant cancers. Since the 1980’s, survival has not improved.

A 1950’s study from the Veterans Administration (VA) Lung Study Group determined 2 subtypes of SCLC—LS-SCLC and ES-SCLC. Between the 2 subtypes, approximately 70% of patients with SCLC have ES-SCLC, which is distinguished as having malignant pleural or pericardial effusions and hematogenous metastases.

Cisplatin is a common radiosensitizer to treat the LS-SCLC and ES-SCLC. However, the less toxic carboplatin-based regime is gaining increased favorability as an ES-SCLC immunotherapeutic. To assess the benefit of one agent over the other, the study investigatrors aimed to evaluate carboplatin against cisplatin in LS-SCLC and ES-SCLC for OS.

Among patients aged 70 years and older, there was no significant difference in OS. Median OS was 6.36 and 8.47 months for cisplatin and carboplatin, respectively. Additionally, among ES-SCLC patients treated with cisplatin, the median OS was 8.45 months—this value was slightly greater at 8.51 months for carboplatin. In LS-SCLC patients, the median OS for cisplatin was 26.92 months, and 25.58 months for carboplatin patients.

During the trial, researchers studied 4408 SCLC patients from the National VA Cancer Cube Registry, defining the primary endpoint as OS. Secondary endpoints include OS according to the Eastern Cooperative Oncology Group performance status, age, and laterality.

The results suggest that cisplatin-based therapies and carboplatin-based therapies are not superior for OS in either ES-SCLC or LS-SCLC. However, in subgroups, cisplatin-based palliative chemotherapy was associated with worse survival outcomes in patients aged 70 years and older with ES-SCLC. Further, the data suggests that carboplatin could be a better treatment for ES-SCLC, especially in young and fit patients.

“All other subgroup analyses showed no survival differences between the 2 chemotherapy regimens, including in young and fit patients,” the study authors wrote.

The authors noted that the study includes important limitations. Retrospective studies usually risk having bias—in this case, the VA population is mainly comprised of patients who are White and older male, so the results for this population may not be generalizable to all populations. Additionally, the study did not use individual patient records, had a lack of data on radiation and chemotherapy dosing, and there was no follow-up and adverse events.

“Large-scale prospective studies are needed to definitely compare carboplatin-based and cisplatin-based regimens for the treatment of SCLC,” study authors wrote in the report. “However, the favorable toxicity profile of carboplatin and comparable OS support its use in both LS-SCLC and ES-SCLC.”

Reference

Azar I, Yaxdanpanah O, Jang H, et al. Comparison of Carboplatin With Cisplatin in Small Cell Lung Cancer in US Veterans. JAMA Netw Open. 2022;5(10):e2237699. doi:10.1001/jamanetworkopen.2022.37699