Metro Giulio, Addeo Alfredo, Signorelli Diego, Gili Alessio, Economopoulou Panagiota, Roila Fausto, Banna Giuseppe, De Toma Alessandro, Rey Cobo Juliana, Camerini Andrea, Christopoulou Athina, Lo Russo Giuseppe, Banini Marco, Galetta Domenico, Jimenez Beatriz, Collazo-Lorduy Ana, Calles Antonio, Baxevanos Panagiotis, Linardou Helena, Kosmidis Paris, Garassino Marina C, Mountzios Giannis
Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
Department of Oncology, Geneva University Hospital, Geneva, Switzerland.
J Thorac Dis. 2019 Dec;11(12):4972-4981. doi: 10.21037/jtd.2019.12.23.
In this real-world multicenter study we addressed the activity of post-progression anticancer treatments after first-line pembrolizumab in advanced non-small cell lung cancer (NSCLC) patients with PD-L1 ≥50%.
Clinico-pathological data of PD-L1 ≥50% advanced NSCLCs who failed first-line pembrolizumab were collected in 14 Oncologic Centers from different European countries. Types of subsequent anticancer treatment and outcomes on salvage chemotherapy or pembrolizumab beyond progression with or without the addition of local ablative therapies were reported.
Out of 173 patients, 100 had progressed on pembrolizumab, of which 60 patients (60%) met eligibility criteria and were treated with either salvage chemotherapy (42/60, 70%) or pembrolizumab beyond progression (18/60, 30%). Overall, median age was 66 years, 63.3% were male, 60.0% had a performance status of 0-1, 88.3% were smokers and 61.7% had adenocarcinoma histology. In patients evaluable for response, objective response rate to salvage chemotherapy was 41.9%, with no significant difference according to the type of regimen (42.9% for platinum-based and 40.0% for single-agent chemotherapy). Median progression-free survival (PFS) to salvage chemotherapy was 4.5 months. Among patients treated with pembrolizumab beyond progression, 13 out of 18 patients (72.2%) had progressive disease in ≤2 organ sites, of whom 9 (69.2%) were managed with the addition of local ablative therapies consisting of radiation at progressive lesion(s). No significant difference was noted in terms of post-progression survival between the salvage chemotherapy and the pembrolizumab beyond progression groups of patients (6.9 versus 8.1 months, respectively, P=0.08).
In PD-L1 ≥50% advanced NSCLCs who progress on first-line pembrolizumab, salvage chemotherapy is associated with a remarkable anticancer activity, while select patients may benefit from continuation of pembrolizumab beyond progression, with the possible addition of local ablative radiotherapy in oligoprogressive cases.
在这项真实世界的多中心研究中，我们探讨了一线帕博利珠单抗治疗后，程序性死亡受体1配体（PD-L1）≥50%的晚期非小细胞肺癌（NSCLC）患者接受进展后抗癌治疗的活性。
收集了来自不同欧洲国家的14个肿瘤中心中一线帕博利珠单抗治疗失败且PD-L1≥50%的晚期NSCLC患者的临床病理数据。报告了后续抗癌治疗的类型以及挽救性化疗或进展后使用帕博利珠单抗（无论是否联合局部消融治疗）的结果。
在173例患者中，100例在接受帕博利珠单抗治疗后出现疾病进展，其中60例患者（60%）符合入选标准，接受了挽救性化疗（42/60，70%）或进展后使用帕博利珠单抗治疗（18/60，30%）。总体而言，中位年龄为66岁，63.3%为男性，60.0%的患者体能状态为0-1，88.3%为吸烟者，61.7%的患者组织学类型为腺癌。在可评估疗效的患者中，挽救性化疗的客观缓解率为41.9%，根据治疗方案类型无显著差异（铂类为基础的化疗方案为42.9%，单药化疗为40.0%）。挽救性化疗的中位无进展生存期（PFS）为4.5个月。在进展后接受帕博利珠单抗治疗的患者中，18例患者中有（72.2%）13例在≤2个器官部位出现疾病进展，其中9例（69.2%）接受了局部消融治疗，即在进展病灶处进行放射治疗。在挽救性化疗组和进展后使用帕博利珠单抗治疗组的患者中，进展后生存期无显著差异（分别为6.9个月和8.1个月，P=0.08）。
在一线帕博利珠单抗治疗后出现进展的PD-L1≥50%的晚期NSCLC患者中，挽救性化疗具有显著的抗癌活性，而部分患者可能从进展后继续使用帕博利珠单抗治疗中获益，在寡进展性病例中可能联合局部消融放疗。
