In patients with extensive stage small cell lung cancer (SCLC), should immunotherapy be discontinued during consolidation thoracic radiotherapy?

From the Guidelines

For patients with extensive stage small cell lung cancer (ES-SCLC), immunotherapy should be continued during consolidation thoracic radiotherapy, as it has been shown to improve overall survival and progression-free survival, with a favorable risk-benefit profile, as demonstrated in the most recent and highest quality study 1. The standard approach is to maintain immunotherapy, such as durvalumab, while delivering consolidation thoracic radiation to responders after platinum-etoposide chemotherapy plus immunotherapy.

• The radiation is usually given at doses of 30 Gy in 10 fractions or similar regimens.
• Continuing immunotherapy during radiation may actually enhance treatment efficacy through potential synergistic effects, as radiation can increase tumor antigen presentation and enhance immune recognition.
• However, close monitoring for pneumonitis is essential, as both immunotherapy and thoracic radiation can cause lung inflammation. Some key points to consider when making this decision include:
• The patient's performance status and tolerance of previous treatments.
• The potential benefits of continuing immunotherapy, including improved overall survival and progression-free survival.
• The potential risks of continuing immunotherapy, including pneumonitis and other immune-related adverse events. As noted in the study by Khurshid et al 1, the benefits of continuing immunotherapy during consolidation thoracic radiotherapy outweigh the risks, and this approach is supported by the most recent and highest quality evidence. Additionally, the NCCN guidelines insights: small cell lung cancer, version 2.2018 1 and the systemic therapy for small-cell lung cancer: asco-ontario health (cancer care ontario) guideline 1 also provide guidance on the management of ES-SCLC, but the most recent and highest quality study 1 takes precedence in informing this decision.

From the Research

Immunotherapy Discontinuation During Consolidation Thoracic Radiotherapy

• There is no clear evidence to suggest that immunotherapy should be discontinued during consolidation thoracic radiotherapy in patients with extensive stage small cell lung cancer (SCLC) 2, 3, 4, 5, 6.
• Studies have shown that consolidative thoracic radiation therapy (TRT) can be safely combined with immunotherapy, with low rates of toxicity and improved overall survival (OS) and progression-free survival (PFS) 3, 4.
• The use of consolidative TRT after first-line chemoimmunotherapy has been associated with a significantly longer OS and PFS compared to systemic therapy alone 2, 3.
• Preclinical data suggest that radiotherapy can induce anti-tumor immune responses, supporting the combination of TRT and immunotherapy 3.
• The optimal timing and dose of consolidative TRT in combination with immunotherapy are still unclear and require further study 5, 6.

Key Findings

• Consolidative TRT was associated with a significantly longer OS and PFS compared to systemic therapy alone in patients with extensive stage SCLC 2, 3.
• The combination of TRT and immunotherapy was well-tolerated, with low rates of toxicity 3, 4.
• Higher doses of consolidative TRT (45 Gy) were associated with better OS and PFS compared to lower doses (30-36 Gy) 6.

Future Directions

• Further studies are needed to determine the optimal timing and dose of consolidative TRT in combination with immunotherapy in patients with extensive stage SCLC 2, 3, 4, 5, 6.
• The role of consolidative TRT in the era of immunotherapy requires further clarification 5, 6.