Department of Medical Oncology, Chinese PLA General Hospital, Beijing, 100853, China.
Beijing Chest Hospital, Beijing, 101149, China.
Cancer Immunol Immunother. 2021 Oct;70(10):2971-2980. doi: 10.1007/s00262-021-02852-4. Epub 2021 Mar 19.
Rationale exists for combining immune checkpoint inhibitors and PARP inhibitors (PARPi), and results of clinical trials in ovarian cancer are promising, but data in other cancers are limited.
Efficacy and safety of PARPi/anti-PD-1 in advanced solid tumors were retrospectively analyzed. The efficacy measures included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS).
This retrospective study included data from 40 patients. The ORR was 27.5% (95% CI, 13.0-42.0%), with a DCR of 85.0% (95% CI, 73.4-96.6%). Except four patients in first-line treatment (three with PR and one with SD), the ORR of ≥second-line treatment, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) was 22.2%, 23.1% and 28.6%, and the DCR was 83.3%, 84.6% and 71.4%, separately. The median PFS of all patients, ≥second-line treatment, NSCLC and SCLC was 4.6 m, 4.2 m, 4.5 m and 3.7 m. The median OS was 9.4 m, 11.4 m, 12.7 m and 5.4 m, respectively. Multivariable analysis revealed that BRCA1/2 mutation was positively correlated with ORR (P = 0.008), and LDH≥250U/L was negatively correlated with lowered DCR (P = 0.018), while lymphocyte number, ECOG and LDH significantly influenced both PFS and OS. We found that the possible resistant mechanisms were sarcomatous degeneration and secondary mutation, including BRCA2 truncation mutation, A2M, JAK1,T790M, KEAP1 and mTOR mutation. 37.5% patients had ≥grade 3 adverse events.
PARPi/anti-PD-1 is an effective and tolerable method for patients with advanced solid tumors, and BRCA1/2 is a potential biomarker.
联合免疫检查点抑制剂和 PARP 抑制剂（PARPi）具有一定的理论基础，且在卵巢癌中的临床试验结果令人鼓舞，但其他癌症的数据有限。
回顾性分析了 PARPi/抗 PD-1 在晚期实体瘤中的疗效和安全性。疗效评估指标包括客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）。
本回顾性研究纳入了 40 例患者的数据。ORR 为 27.5%（95%CI，13.0-42.0%），DCR 为 85.0%（95%CI，73.4-96.6%）。除一线治疗的 4 例患者（3 例 PR，1 例 SD）外，≥二线治疗、非小细胞肺癌（NSCLC）和小细胞肺癌（SCLC）的 ORR 分别为 22.2%、23.1%和 28.6%，DCR 分别为 83.3%、84.6%和 71.4%。所有患者、≥二线治疗、NSCLC 和 SCLC 的中位 PFS 分别为 4.6 个月、4.2 个月、4.5 个月和 3.7 个月，中位 OS 分别为 9.4 个月、11.4 个月、12.7 个月和 5.4 个月。多变量分析显示，BRCA1/2 突变与 ORR 呈正相关（P=0.008），LDH≥250U/L 与降低的 DCR 呈负相关（P=0.018），而淋巴细胞计数、ECOG 和 LDH 显著影响 PFS 和 OS。我们发现可能的耐药机制是肉瘤样变性和继发性突变，包括 BRCA2 截断突变、A2M、JAK1、T790M、KEAP1 和 mTOR 突变。37.5%的患者出现≥3 级不良事件。
PARPi/抗 PD-1 是晚期实体瘤患者有效且耐受良好的治疗方法，BRCA1/2 是一种潜在的生物标志物。
