Vacher Laure, Bernadach Maureen, Molnar Ioana, Passildas-Jahanmohan Judith, Dubray-Longeras Pascale
Oncology Department Centre Jean Perrin Clermont-Ferrand France.
UFR Médecine University Clermont Auvergne Clermont-Ferrand France.
Health Sci Rep. 2024 Jan 25;7(1):e1825. doi: 10.1002/hsr2.1825. eCollection 2024 Jan.
The treatment of metastatic non-small-cell lung cancer (NSCLC) has been revolutionized by the arrival of immune checkpoint inhibitors (ICI). For patients without immune related adverse events (irAEs), it is recommended to continue the treatment as long as it provides clinical benefit or until unacceptable toxicity appears. The aim of our study was to evaluate survival data among patients with advanced or metastatic NSCLC following ICI discontinuation for reasons of long-term response or toxicity (irAEs).
We included all patients with advanced or metastatic NSCLC treated with nivolumab and pembrolizumab at the Centre Jean Perrin, Clermont-Ferrand, France (January 1, 2016 to May 31, 2019). We focused on two groups in this study population: "Voluntary treatment discontinuation" (medical decision as a result of long-term response and patient decision) and "Treatment discontinuation due to toxicity" (irAEs). The primary endpoint was to evaluate the postdiscontinuation outcomes of these two groups: progression-free survival (PFS) and overall survival (OS), and rechallenge in the "voluntary discontinuation" group.
The final analysis concerned 146 patients, including 10 (7%) in the "discontinuation due to toxicity" group, 11 (8%) in the "voluntary discontinuation" group, 100 (68%) who discontinued treatment as a result of progression and 25 (17%) whose treatment was still on-going. The median PFS in the "discontinuation due to toxicity" group was not reached, and in the "voluntary discontinuation" group ( = 11) was 37 months ( = 0.4), versus 2 months in the progression group ( < 0.001). The median OS in "discontinuation due to toxicity," and in the "voluntary discontinuation" groups was not reached ( = 0.5), versus 10 months in the progression group ( < 0.001).
Treatment discontinuation following long-term response to ICI treatment showed sustained response and long-term survival after discontinuation. The incidence of irAEs was associated with better long-term survival, even after ICI discontinuation.
免疫检查点抑制剂（ICI）的出现彻底改变了转移性非小细胞肺癌（NSCLC）的治疗方式。对于没有免疫相关不良事件（irAE）的患者，建议只要治疗有临床获益就持续进行，直至出现不可接受的毒性反应。我们研究的目的是评估因长期缓解或毒性反应（irAE）而停用ICI的晚期或转移性NSCLC患者的生存数据。
我们纳入了法国克莱蒙费朗让·佩兰中心（2016年1月1日至2019年5月31日）所有接受纳武单抗和派姆单抗治疗的晚期或转移性NSCLC患者。在这个研究人群中，我们关注两组：“自愿停药”（因长期缓解由医生决定及患者决定停药）和“因毒性反应停药”（irAE）。主要终点是评估这两组停药后的结局：无进展生存期（PFS）和总生存期（OS），以及“自愿停药”组的再次挑战用药情况。
最终分析涉及146例患者，其中“因毒性反应停药”组10例（7%），“自愿停药”组11例（8%），因疾病进展停药100例（68%），治疗仍在进行的25例（17%）。“因毒性反应停药”组的中位PFS未达到，“自愿停药”组（n = 11）为37个月（HR = 0.4），而疾病进展组为2个月（P < 0.001）。“因毒性反应停药”组和“自愿停药”组的中位OS均未达到（P = 0.5），疾病进展组为10个月（P < 0.001）。
ICI治疗长期缓解后停药显示出停药后持续缓解和长期生存。即使在停用ICI后，irAE的发生也与更好的长期生存相关。
