Zhao Lingdi, Ma Baozhen, Yang Yonghao, Li Tiepeng, Han Lu, Gao Quanli
Department of Immunotherapy, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
Front Oncol. 2020 Apr 21;10:507. doi: 10.3389/fonc.2020.00507. eCollection 2020.
Programmed cell death protein 1(PD-1) blockade has become a standard second-line treatment option for patients with advanced non-small cell lung cancer (NSCLC) without a driver gene mutation. Previous clinical studies showed that the objective response rate (ORR) of PD-1 blockade as second-line treatment for patients with NSCLC was ~20%, and the median progression-free survival (PFS) was ~4 months, with most patients eventually developing a resistance to PD-1 blockade. Although the ORR to chemotherapy after PD-1 blockade resistance was relatively high, the survival time of patients could not be significantly prolonged. Clinical oncologists are unclear about which treatment regimen should be selected after PD-1 blockade failure. Here, we report about a patient with advanced NSCLC and initial PD-1 blockade resistance who was observed to have a rapid partial response (PR) following one dose of chemotherapy and subsequent PD-1 blockade treatment. A 70-year-old woman with a history of left lower lobe lung surgery in March 2018 (pathological stage T1N2M0, EGFR wild-type) presented to our hospital. After six cycles of adjuvant chemotherapy, multiple nodules in both the lungs developed, and were suspected to be metastatic lesions. After another 2 months, the nodules in both the lungs enlarged. From November 2018 to March 2019, the patient received six cycles of pembrolizumab, and computed tomography (CT) confirmed a progressive disease status. She was then managed with 260 mg/m albumin paclitaxel once every 3 weeks. Subsequently, chemotherapy was discontinued after one cycle owing to grade three neuromuscular toxicity. Follow-up CT revealed a stable disease in May 2019. She then received another six cycles of pembrolizumab, which resulted in a PR. Chemotherapy may play a role in reversing PD-1 blockade resistance. If failure of PD-1 blockade occurs at first, re-administration of PD-1 blockade may be implemented if first followed by several cycles of chemotherapy. Because there are few reports on the use of chemotherapy to reverse PD-1 resistance, it is necessary to conduct clinical studies with larger patient cohorts to investigate whether chemotherapy can reverse PD-1 blockade resistance.
程序性细胞死亡蛋白1（PD-1）阻断疗法已成为晚期无驱动基因突变的非小细胞肺癌（NSCLC）患者的标准二线治疗选择。既往临床研究表明，PD-1阻断疗法作为NSCLC患者的二线治疗，客观缓解率（ORR）约为20%，中位无进展生存期（PFS）约为4个月，大多数患者最终会对PD-1阻断产生耐药。尽管PD-1阻断耐药后化疗的ORR相对较高，但患者的生存时间无法显著延长。临床肿瘤学家尚不清楚PD-1阻断失败后应选择哪种治疗方案。在此，我们报告1例晚期NSCLC且初始存在PD-1阻断耐药的患者，该患者在接受1个周期化疗及后续PD-1阻断治疗后出现快速部分缓解（PR）。1例70岁女性，有2018年3月左下肺手术史（病理分期T1N2M0，EGFR野生型），来我院就诊。辅助化疗6个周期后，双肺出现多个结节，怀疑为转移灶。再过2个月，双肺结节增大。2018年11月至2019年3月，该患者接受了6个周期的帕博利珠单抗治疗，计算机断层扫描（CT）证实疾病进展。随后每3周给予260mg/m白蛋白紫杉醇治疗。1个周期后因3级神经肌肉毒性停止化疗。2019年5月随访CT显示疾病稳定。之后她又接受了6个周期的帕博利珠单抗治疗，结果出现PR。化疗可能在逆转PD-1阻断耐药中发挥作用。如果一开始出现PD-1阻断失败，可先进行几个周期化疗，之后再重新使用PD-1阻断疗法。由于关于使用化疗逆转PD-1耐药的报道较少，有必要开展更大患者队列的临床研究，以调查化疗是否能逆转PD-1阻断耐药。
