Olivier Timothée, Prasad Vinay
Oncology Service, Geneva University Hospital, 4 Gabrielle-Perret-Gentil Street, 1205, Geneva, Switzerland.
Department of Epidemiology and Biostatistics, University of California San Francisco, 550 16th St, 2nd Fl, San Francisco, CA, 94158, USA.
Transl Oncol. 2025 Jun;56:102397. doi: 10.1016/j.tranon.2025.102397. Epub 2025 Apr 16.
The LUNAR trial investigated the addition of Tumor Treating Fields (TTFs) to "standard therapy" in patients with metastatic lung cancer after at least one line of platinum-based chemotherapy. The "standard therapy" was either an anti-PD(L)1 therapy (immunotherapy) or docetaxel. The addition of TTFs provided a 3.3 months median survival gain. We raised concerns about LUNAR results internal and external validity. First, patient selection and the control arm do not mirror current practice. Two-thirds of patients did not receive prior immunotherapy, which is standard in first-line treatment. Also, the "choice" of the "standard therapy" was restricted by drug availability, resulting in 41 % of patients not receiving immunotherapy during the trial - those allocated to receive docetaxel - had no prior exposure to immunotherapy. Some patients may have harbored actionable mutations, and did not receive targeted therapy. Second, we raised statistical questions. The sample size was shrunk after an unplanned analysis, with unshared and unclear justifications. The decision may have been influenced by a chance deviation in data favoring the intervention. Also, as significantly more patients were censored after withdrawals in the TTFs group, informative censoring could have amplified the survival gain. Third and last, without a sham-control design (the equivalent of placebo for devices), it's hard to isolate the impact of TTFs from the extra-attention associated with its administration (continuous 24/7 support, frequent home-based interactions). Overall, LUNAR do not apply to clinical settings where immunotherapy and molecular testing is offered, and many factors may have artificially boosted the reported survival gain. A sham-controlled trial is needed to answer whether TTFs are beneficial.
LUNAR试验研究了在接受至少一线铂类化疗后的转移性肺癌患者中，在“标准治疗”基础上加用肿瘤治疗电场（TTFs）的效果。“标准治疗”为抗PD(L)1治疗（免疫治疗）或多西他赛。加用TTFs使患者的中位生存期延长了3.3个月。我们对LUNAR试验结果的内部和外部有效性表示担忧。首先，患者选择和对照组不能反映当前的临床实践。三分之二的患者未接受过先前的免疫治疗，而这在一线治疗中是标准做法。此外，“标准治疗”的“选择”受药物可及性限制，导致41%的患者在试验期间未接受免疫治疗——那些被分配接受多西他赛治疗的患者——之前未接触过免疫治疗。一些患者可能存在可靶向治疗的突变，但未接受靶向治疗。其次，我们提出了统计学问题。在一次计划外分析后样本量缩小，理由未公开且不明确。这一决定可能受到了数据中有利于干预措施的偶然偏差的影响。此外，由于TTFs组中更多患者在退出研究后被 censored，信息删失可能放大了生存期的延长。第三也是最后一点，由于没有假对照设计（类似于器械的安慰剂），很难将TTFs的影响与与其给药相关的额外关注（持续的全天候支持、频繁的居家互动）区分开来。总体而言，LUNAR试验结果不适用于提供免疫治疗和分子检测的临床环境，许多因素可能人为地提高了报告的生存期延长效果。需要进行假对照试验来回答TTFs是否有益。 （注：原文中“censored”一词在医学研究语境中有特定含义，这里暂保留英文未翻译，需结合具体医学知识准确理解，可根据实际情况译为“删失”等合适表述 ）
