PD-1抑制剂逆转安罗替尼获得性耐药2例报道

陈倩 李碧慧 康马飞

[摘要] 在本报道中，2例晚期口腔腺癌患者化疗后进展，改用安罗替尼治疗，肿瘤有缩小（疗效评价为SD）。病例1于安罗替尼治疗后2.8个月出现耐药，肿瘤进展，给予PD-1抑制剂（特瑞普利单抗）治疗1个周期，后再次使用安罗替尼治疗，肿瘤再次缩小（疗效评价为SD），目前仍然在维持治疗中。安罗替尼治疗的第1次无进展生存时间（PFS1）为2.8个月，第2次无进展生存时间（PFS2）为12.8+个月。病例2于安罗替尼治疗后15.5个月出现耐药，肿瘤进展，给予PD-1抑制剂（卡瑞利珠单抗）治疗4个周期，后再次使用安罗替尼治疗，肿瘤再次缩小（疗效评价为SD），目前仍然在维持治疗中。安罗替尼治疗的第1次无进展生存时间（PFS1）为15.5个月，第2次无进展生存时间（PFS2）为6.0+个月。这些病例显示，PD-1抑制剂可能逆转安罗替尼的获得性耐药，值得进一步研究。

[关键词] PD-1抑制剂;安罗替尼;耐药性;特瑞普利;卡瑞利珠

[Abstract] In this report， two patients with advanced oral adenocarcinoma progressed after chemotherapy and were switched to anlotinib. The tumors shrank（the efficacy evaluation was SD）. Case 1 developed drug resistance 2.8 months after treatment with Anlotinib and the tumor progressed. The patient was given PD-1 inhibitor（treplimumab） for 1 cycle， and then treated with anlotinib again. The tumor shrank again（the efficacy evaluation was SD）. The patient was still under maintenance treatment. The first progression-free survival time（PFS1） of anlotinib treatment was 2.8 months， and the second progression-free survival time（PFS2） was 12.8+ months. Case 2 developed drug resistance at 15.5 months after Anlotinib treatment， and the tumor progressed. The PD-1 inhibitor（carrelizumab） was given for 4 cycles， and then anlotinib was used again. The tumor shrank again（the efficacy evaluation was SD）. The patient was still under maintenance treatment. The first progression-free survival time（PFS1） of anlotinib treatment was 15.5 months， and the second progression-free survival time（PFS2） was 6.0+ months. These cases suggest that PD-1 inhibitors may reverse the acquired resistance of anlotinib， which is worthy of further study.

[Key words] PD-1 inhibitors; Anlotinib; Drug resistance; Treplimumab; Carrelizumab

安羅替尼（Anlotinib）是一种口服多靶点酪氨酸激酶小分子抑制剂，对肿瘤血管生成和生长具有广泛的抑制作用。在中国，安罗替尼已被批准用于局部晚期或转移性非小细胞肺癌的三线治疗。在中国、美国和意大利，安罗替尼也正在进行各种肉瘤和癌的Ⅱ期和（或）Ⅲ期临床研究[1]。程序性细胞死亡蛋白1（Programmed cell death protein 1，PD-1）抑制剂在肺癌等肿瘤的治疗中也显示了较好的疗效，特别是程序性细胞死亡配体1（Programmed cell death ligand 1，PD-L1）表达的肿瘤效果较好[2-3]。然而，临床中一些化疗后进展或拒绝化疗的晚期恶性肿瘤患者，在没有标准治疗方案的情况下，临床医师可能在患者和家属要求下尝试新药治疗。……