Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojimaminamimachi, Chuo-ku, Kobe-shi, Hyogo, 650-0047, Japan.
Internal Medicine III, Wakayama Medical University, 811-1, Kimiidera, Wakayama City, Wakayama, 641-8509, Japan.
BMC Cancer. 2021 Apr 1;21(1):346. doi: 10.1186/s12885-021-08048-4.
Despite the wide-spread use of immune checkpoint inhibitors (ICIs) in cancer chemotherapy, reports on patients developing acquired resistance (AR) to ICI therapy are scarce. Therefore, we first investigated the characteristics associated with shorter durable responses of ICI treatment and revealed the clinical patterns of AR and prognosis of the patients involved.
We conducted a retrospective multi-center cohort study that included NSCLC patients with PD-L1 tumor proportion scores of ≥50% who received first-line pembrolizumab and showed response to the therapy. Among patients showing response, progression-free survival (PFS) was investigated based on different clinically relevant factors. AR was defined as disease progression after partial or complete response based on Response Evaluation Criteria in Solid Tumors. Among patients with AR, patterns of AR and post-progression survival (PPS) were investigated. Oligoprogression was defined as disease progression in up to 5 individual progressive lesions.
Among 174 patients who received first-line pembrolizumab, 88 showed response and were included in the study. Among these patients, 46 (52%) developed AR. Patients with old age, poor performance status (PS), at least 3 metastatic organs, or bone metastasis showed significantly shorter PFS. Among 46 patients with AR, 32 (70%) developed AR as oligoprogression and showed significantly longer PPS than those with non-oligoprogressive AR.
Patients with old age, poor PS, at least 3 metastatic organs, or bone metastasis showed shorter durable responses to pembrolizumab monotherapy. Oligoprogressive AR was relatively common and associated with better prognosis. Further research is required to develop optimal approaches for the treatment of these patients.
尽管免疫检查点抑制剂（ICIs）在癌症化疗中广泛应用，但关于患者对ICI 治疗产生获得性耐药（AR）的报道很少。因此，我们首先调查了与 ICI 治疗持久反应较短相关的特征，并揭示了 AR 的临床模式和涉及患者的预后。
我们进行了一项回顾性多中心队列研究，纳入了 PD-L1 肿瘤比例评分≥50%的接受一线 pembrolizumab 治疗并对治疗有反应的 NSCLC 患者。在有反应的患者中，根据不同的临床相关因素研究无进展生存期（PFS）。AR 定义为根据实体瘤反应评估标准在部分或完全缓解后疾病进展。在有 AR 的患者中，研究了 AR 的模式和后进展生存期（PPS）。寡进展定义为最多 5 个单独进展病变的疾病进展。
在接受一线 pembrolizumab 治疗的 174 名患者中，有 88 名显示有反应并纳入研究。这些患者中，有 46 名（52%）发生了 AR。年龄较大、一般状况较差（PS）、至少有 3 个转移器官或骨转移的患者 PFS 明显较短。在 46 名有 AR 的患者中，有 32 名（70%）发生了寡进展性 AR，与非寡进展性 AR 相比，PPS 明显更长。
年龄较大、PS 较差、至少有 3 个转移器官或骨转移的患者对 pembrolizumab 单药治疗的持久反应较短。寡进展性 AR 比较常见，与较好的预后相关。需要进一步研究以开发这些患者的最佳治疗方法。
