Systemic therapy for SCLC: is platinum/etoposide the limit?

Outcomes for patients with small‐cell lung cancer remain poor and advances in treatments have not kept pace with those seen for other cancers. The main improvements in outcomes have been related to use of radiotherapy, though chemotherapy remains the cornerstone of treatment for the majority of patients. A platinum‐based chemotherapy regimen is the standard of care, based on the data from 4 meta‐analyses and systematic reviews. However, a recent Cochrane review of 29 randomised controlled trials reported no significant survival benefit for platinum based treatment at 6, 12 or 24 months. It is unclear whether cisplatin and carboplatin can be used interchangeably, and the only study to address this was not powered for equivalence. Combined modality treatment with cisplatin‐based chemotherapy and early concurrent radiotherapy remains the standard of care for patients with limited stage disease, based on a number of randomised controlled trials and systematic reviews. Any new drug would almost certainly need to be deliverable with concurrent radiotherapy to make a significant impact in limited stage disease The role of maintenance chemotherapy remains unclear, with concerns about toxicity. However, a meta‐analysis of 14 randomised studies encompassing 2550 patients reported a 4% survival benefit at 2 years. For patients with extensive stage (EDSCLC) disease but a good performance status, 4‐6 cycles of platinum based chemotherapy is a standard of care. There is no clear benefit to adding a third of fourth drug to standard treatment, or to alternating treatments. Strategies to evaluate new agents in EDSCLC have usually involved either addition of the new drug to the plati‐num‐etoposide combination, or substitution for etoposide. There is no clear benefit to the combination of platinum topotecan over platinum‐etoposide in first line treatment, thought topotecan is the only drug licensed for second line therapy, and showed a clear benefit in quality of life and survival over best supportive care. Two studies evaluating the addition of paclitaxel to platinum‐etopo‐side reported increased toxicity but no survival benefit. The combination of car‐boplatin‐pemetrexed was found to be inferior to carboplatin‐etoposide and a large phase 3 study was closed early by the Data Safety Monitoring Committee. The median overall survival was 8.1 months for carboplatin‐pemetrexed and 10.6 months for carboplatin‐etoposide. Irinotecan has shown activity in an Asian population of patients, but no benefit was seen in a large phase 3 study carried out by SWOG. A recent meta‐analysis reported that platinum‐irinotecan is not inferior to platinum‐etoposide. Amrubicin, a synthetic anthracycline has shown significant activity in the second‐line setting, both in the sensitive and resistant/ refractory patients. A recent first line randomised phase II study showed a response rate of 77% for cisplatin‐amrubicin versus 63% for cisplatin‐etoposide. A large phase III study in second‐line setting comparing amrubicin with topote‐can has completed accrual and the result of this will impact on future study design in the first‐line setting. Platinum‐etoposide chemotherapy remains the standard of care for the majority of patients with small cell lung cancer.