Medical Oncology Department, University Hospital Lozano Blesa, Avda. San Juan Bosco, 15, 50009, Zaragoza, Spain.
Medical Oncology Department, Hospital Universitario La Paz-IDIPAZ, Madrid, Spain.
Clin Transl Oncol. 2020 May;22(5):759-771. doi: 10.1007/s12094-019-02191-y. Epub 2019 Jul 31.
Immunotherapy-based approaches are standard first-line treatments for advanced/metastatic lung cancer or for chemoradiotherapy consolidation in locally advanced disease. Uncertainty on how to treat patients at disease progression prompted us to develop a consensus document on post-immunotherapy options in Spain for patients with advanced wild-type lung adenocarcinoma.
After extensive literature review, a 5-member scientific committee generated 33 statements in 4 domains: general aspects (n = 4); post-durvalumab in locally advanced disease (n = 6); post-first-line immunotherapy ± chemotherapy in advanced/metastatic disease (n = 11); and post-first-line platinum-based chemotherapy in advanced/metastatic disease (n = 12). A panel of 26 lung cancer experts completed 2 Delphi iterations through an online platform rating their degree of agreement/disagreement (first-round scale 1-5 and second-round scale 1-4, 1 = strongly disagree, 4/5 = strongly agree) for each statement. Second-round consensus: ≥ 70% of responses were in categories 1/2 (disagreement) or 3/4 (agreement).
Consensus was reached for 2/33 statements in the first Delphi round and in 29/31 statements in the second round. Important variables informing treatment at disease progression with an immunotherapy-based treatment include: disease aggressiveness, previous treatment, accumulated toxicity, progression-free interval, PD-L1 expression, and tumour mutational burden. A platinum-based chemotherapy should follow a first-line immunotherapy treatment without chemotherapy. Treatment with docetaxel + nintedanib may be appropriate post-durvalumab in refractory patients or following progression to first-line chemotherapy + immunotherapy, or second-line chemotherapy after first-line immunotherapy, or first-line chemotherapy in some patients with low/negative PD-L1 expression, or second-line immunotherapy after first-line chemotherapy.
To support decision making following progression to immunotherapy-based treatment in patients with advanced wild-type lung adenocarcinoma, a consensus document has been developed.
免疫治疗为基础的方法是晚期/转移性肺癌或局部晚期疾病放化疗巩固的标准一线治疗。对于疾病进展时如何治疗患者存在不确定性，促使我们为西班牙晚期野生型肺腺癌患者制定了免疫治疗后选择的共识文件。
经过广泛的文献回顾，由 5 名科学委员会成员在 4 个领域生成了 33 项声明：一般方面（n=4）；局部晚期疾病的度伐利尤单抗治疗后（n=6）；一线免疫治疗±化疗后的晚期/转移性疾病（n=11）；一线铂类化疗后的晚期/转移性疾病（n=12）。一个由 26 名肺癌专家组成的小组通过在线平台完成了 2 轮 Delphi 迭代，对每个声明的同意/不同意程度进行评分（第一轮为 1-5 分，第二轮为 1-4 分，1=强烈不同意，4/5=强烈同意）。第二轮共识：≥70%的应答者在 1/2（不同意）或 3/4（同意）类别中。
在第一轮 Delphi 中，有 2/33 项声明达成共识，在第二轮 Delphi 中，有 29/31 项声明达成共识。在疾病进展时用免疫治疗为基础的治疗方案进行治疗时需要考虑的重要变量包括：疾病侵袭性、既往治疗、累积毒性、无进展生存期、PD-L1 表达和肿瘤突变负荷。在一线免疫治疗后应采用铂类化疗。在难治性患者或一线化疗+免疫治疗后进展、一线免疫治疗后二线化疗、PD-L1 表达低/阴性的部分患者的一线化疗、或一线化疗后二线免疫治疗时，多西他赛+尼达尼布可能是合适的。
为了支持晚期野生型肺腺癌患者免疫治疗后进展时的决策制定，制定了共识文件。
