Department of Radiation Oncology, Dr Negrin University Hospital of Gran Canaria, Las Palmas de Gran Canaria, Spain; Department of Radiation Oncology, ASCIRES Grupo Biomedico, Valencia, Spain; Faculty of Medicine, University of Malaga (UMA), Malaga, Spain.
Department of Radiation Oncology, Dr Negrin University Hospital of Gran Canaria, Las Palmas de Gran Canaria, Spain; Faculty of Medicine, University of Malaga (UMA), Malaga, Spain; Group of Translational Research in Cancer Immunotherapy, Health and Medical Research Centre (CIMES), University of Malaga (UMA), Malaga, Spain; Department of Radiation Oncology, Virgen de la Victoria University Hospital, Malaga, Spain; Institute of Biomedical Research in Malaga (IBIMA), Malaga, Spain.
Int J Radiat Oncol Biol Phys. 2022 Nov 15;114(4):655-665. doi: 10.1016/j.ijrobp.2022.05.013. Epub 2022 May 18.
The percentage of patients with metastatic non-small cell lung cancer (NSCLC) and melanoma who benefit from anti-programmed cell death protein 1 (anti-PD-1) is low owing to resistance mechanisms. SABR has a role in oligoprogressive disease and can improve responses to anti-PD-1. This multicenter prospective observational study aimed to determine whether concomitant anti-PD-1 and SABR to oligoprogressive sites enhance tumor response in metastatic NSCLC and melanoma.
Patients with metastatic NSCLC or melanoma in progression to anti-PD-1 but continuing the same line owing to clinical benefit were referred for palliative SABR. All patients received concomitant pembrolizumab or nivolumab and SABR to 1 to 5 lesions, maintaining anti-PD-1 until further progression, unacceptable toxicity, or medical/patient decision. Objective response rate-complete responses and partial responses-was evaluated during all follow-up according to Response Evaluation Criteria in Solid Tumors 1.1. The abscopal response was evaluated 8 weeks after SABR as a ≥30% reduction in 1 to 2 predefined nonirradiated lesions.
Of the 61 patients enrolled, 50 could be analyzed. With a median follow-up of 32.8 months, objective response rate was 42% (30% complete responses and 12% partial responses). Median progression-free survival was 14.2 months (95% confidence interval, 6.9-29 months). Median overall survival since SABR was 37.4 months (95% confidence interval, 22.9 months-not reached). Abscopal response was 65%, evaluated in 40 patients who fulfilled the criteria.
Combined anti-PD-1 and SABR in oligoprogressive metastatic NSCLC or melanoma can achieve high rates of response and extend the clinical benefit of immunotherapy by delaying further progression and a new systemic therapy. This approach should be assessed in larger randomized trials.
由于耐药机制的存在，转移性非小细胞肺癌（NSCLC）和黑色素瘤患者中受益于抗程序性细胞死亡蛋白 1（抗 PD-1）的比例较低。SABR 在寡进展性疾病中有一定作用，并能提高抗 PD-1 的反应。这项多中心前瞻性观察研究旨在确定同时针对寡进展性部位进行抗 PD-1 和 SABR 是否能增强转移性 NSCLC 和黑色素瘤的肿瘤反应。
由于临床获益而继续使用同一线治疗但对进展期抗 PD-1 药物耐药的转移性 NSCLC 或黑色素瘤患者被推荐接受姑息性 SABR。所有患者均接受 pembrolizumab 或 nivolumab 联合 SABR 治疗 1-5 个病灶，在进一步进展、不可接受的毒性或医疗/患者决定之前继续使用抗 PD-1。根据实体瘤反应评估标准 1.1，在所有随访期间评估客观缓解率-完全缓解和部分缓解。SABR 后 8 周评估远隔效应，定义为 1-2 个预先定义的未照射病灶至少减少 30%。
在入组的 61 例患者中，50 例可进行分析。中位随访 32.8 个月，客观缓解率为 42%（完全缓解率 30%，部分缓解率 12%）。无进展生存期的中位值为 14.2 个月（95%置信区间，6.9-29 个月）。自 SABR 以来的中位总生存期为 37.4 个月（95%置信区间，22.9 个月-未达到）。40 例符合条件的患者评估了远隔效应，其远隔效应率为 65%。
在寡进展性转移性 NSCLC 或黑色素瘤中联合使用抗 PD-1 和 SABR 可以实现高反应率，并通过延迟进一步进展和新的全身治疗来延长免疫治疗的临床获益。这种方法应在更大的随机试验中进行评估。
