The "Expert Consensus on Radiotherapy Combined with Immunotherapy for Unresectable Lung Cancer (2024 Edition)" was recently released under the guidance of Academician Jinming Yu from Shandong Cancer Hospital, Professor Ying Cheng from Jilin Cancer Hospital, and Professor Liang’an Chen from the Chinese PLA General Hospital. This consensus provides evidence and guidance for the application of radiotherapy combined with immunotherapy in clinical practice. In an exclusive interview with Oncology Frontier, Dr. Zhiyong Ma from Henan Cancer Hospital discussed the optimal duration of immunotherapy as consolidation therapy, individualized treatment in radiotherapy combined with immunotherapy, and future research directions.

Oncology Frontier: In patients with unresectable lung cancer, the duration of post-chemoradiotherapy immunotherapy varies. How do you view the differences between one-year and two-year treatment durations in terms of efficacy and safety?

Dr. Zhiyong Ma: The treatment landscape for unresectable stage III lung cancer has significantly evolved, largely due to studies such as PACIFIC and GEMSTONE-301. Both studies demonstrated that consolidation immunotherapy following chemoradiotherapy could improve progression-free survival (PFS) and overall survival (OS). The key difference is that PACIFIC used concurrent chemoradiotherapy, while GEMSTONE-301 allowed for sequential chemoradiotherapy. Additionally, PACIFIC set the consolidation duration at one year, while GEMSTONE-301 extended it to two years, prompting discussions about the optimal duration of consolidation therapy.

When assessing the optimal duration, balancing clinical benefits with tolerability is crucial. If a consolidation regimen shows significant efficacy with tolerable side effects, extending the treatment duration may be considered. Clinically, the duration should be individualized: for patients with poorer general condition, one year might be preferred, while those with better overall health, significant clinical benefit, and good tolerability may extend to two years.

A retrospective study including 1,006 patients with stage III NSCLC who received at least one dose of durvalumab after concurrent chemoradiotherapy indicated a trend toward increased benefits with prolonged immunotherapy. However, potential confounding factors in retrospective analyses cannot be overlooked. Furthermore, GEMSTONE-301 included more stage IIIB and IIIC patients, suggesting that patients with more advanced stages may benefit from a two-year course, but further large-scale clinical studies are needed to confirm this.

Currently, there’s limited evidence regarding the optimal duration for post-chemoradiotherapy immunotherapy. Additional studies are necessary to define the risk-benefit balance for one, two, or even longer durations, ensuring individualized treatment for each patient.

Considering the current evidence, the expert group behind the “Expert Consensus on Radiotherapy Combined with Immunotherapy for Unresectable Lung Cancer” recommends 1–2 years of immunotherapy for patients with unresectable stage III NSCLC who remain progression-free after chemoradiotherapy. For patients with stages IIIB and IIIC, two years of consolidation therapy may be considered (consensus level: 97.2%; recommendation grade: II).

Oncology Frontier: What is the current status and research progress of radiotherapy combined with immunotherapy for unresectable lung cancer with different histological types? How can individualized treatment be better implemented in clinical practice?

Dr. Zhiyong Ma: For unresectable stage III NSCLC, concurrent chemoradiotherapy is considered curative, and studies such as PACIFIC and GEMSTONE-301 have provided solid evidence for combining this approach with immunotherapy.

For small cell lung cancer (SCLC), radiotherapy combined with immunotherapy is actively being explored. The phase III ADRIATIC trial showed promising results for durvalumab consolidation after concurrent chemoradiotherapy, with significant PFS and OS benefits and good safety, offering hope for limited-stage SCLC. Similarly, a study presented at ASCO 2024 involving atezolizumab with radiotherapy for extensive-stage SCLC demonstrated new therapeutic breakthroughs, with median PFS exceeding 10 months and median OS reaching 21.4 months.

In clinical practice, the radiotherapy-immunotherapy combination must be tailored to individual patient characteristics. Age and comorbidities, especially for elderly patients, should be carefully evaluated to determine whether they can tolerate standard concurrent chemoradiotherapy; otherwise, sequential therapy may be necessary. The tumor’s biological characteristics, such as driver mutations in NSCLC (e.g., EGFR and ALK-positive), should also be considered, as these patients may derive less benefit from the radiotherapy-immunotherapy combination, with targeted therapies often being more effective.

Exploring “subtraction” strategies from the standard PACIFIC model may help optimize treatment, such as utilizing only immunotherapy for PD-L1 high-expressing patients, which may also yield good survival outcomes. However, this requires further research for validation. Additionally, selecting patients who are likely to benefit, refining risk assessments for pneumonitis and cardiovascular complications, and adjusting treatment plans accordingly will be key directions for future efforts.

Reference

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3.     中国抗癌协会肿瘤多学科诊疗专业委员会, 等. 中华肿瘤防治杂志. 2024(10);31:1223-1238.

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6.Dawei C, et al. 2024 ASCO Annual Meeting. Abstract 8014.

Dr. Zhiyong Ma Chief Physician and Master’s Supervisor, Henan Cancer Hospital Director, Lung Cancer Diagnosis and Treatment Center, Henan Cancer Hospital Standing Member, Lung Cancer Professional Committee, Chinese Anti-Cancer Association Standing Member, NSCLC Committee, Chinese Society of Clinical Oncology