Dudnik Elizabeth, Bar Jair, Moore Assaf, Gottfried Teodor, Moskovitz Mor, Dudnik Julia, Shochat Tzippy, Allen Aaron M, Zer Alona, Rotem Ofer, Peled Nir, Urban Damien
Thoracic Cancer Service, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Front Oncol. 2021 Mar 10;11:603223. doi: 10.3389/fonc.2021.603223. eCollection 2021.
Little is known regarding the outcomes of systemic treatments in BAP1-altered malignant pleural mesothelioma (MPM).
Forty five patients with MPM [group A: eight MPM patients with BAP1 inactivating mutation/copy number loss (FoundationOne CDx/TEMPUSxT), selected from the electronic databases of four Israeli cancer centers (ICC); group B: 37 consecutive (years 2016-2018) MPM patients selected from the electronic databases of two ICC-of those six patients without a BAP1 alteration (group B1) and 31 patients not tested for BAP1 (group B2)] were analyzed for ORR, PFS (mRECIST), and OS with 1-line platinum/pemetrexed+/-antiangiogenic drug (CT, n-28), immune check-point inhibitors (ICPi, n-16) and poly (ADP-ribose) polymerase inhibitors (PARPi, n-4). OS since diagnosis (OSDx) was assessed.
There were no differences in ORR or mPFS with CT between the groups: ORR-50% . 47% . 50% . 47% (p>0.9), mPFS-9.1mo (95% CI, 1.2-16.1) . 9.2mo (95% CI, 2.9-13.3) . 7.2mo (95% CI, 2.3-NR) . 10.9mo (95% CI, 2.9-20.3) (p>0.8) in groups A, B, B1, and B2, respectively. There were no differences in ORR or mPFS with ICPi between the groups: ORR-0% . 27% . 33% . 25% (p>0.2), mPFS-2.5mo (95% CI, 1.4-3.7) . 3.0mo (95% CI, 1.3-10.5) . 2.0mo (95% CI, 1.9-NR) . 4.5mo (95% CI, 0.3-10.5) (p>0.3) in groups A, B, B1, and B2, respectively. In group A, no responses were seen with PARPi; mPFS with PARPi was 1.8mo (95% CI, 1.8-NR). OSDx was 98.3mo (95% CI, 9.7-98.3) . 19.4mo (95% CI, 9.7-47.3) . 18.8mo (95% CI, 8.5-NR) . 19.5mo (95% CI, 8.3-82.2) in groups A, B, B1, and B2, respectively (p>0.3).
BAP1-altered MPM, as compared to non-selected MPM, is characterized by similar efficacy of CT and ICPi. Numerically longer OS in BAP1-altered MPM may reflect favorable tumor biology. No responses were observed with PARPi.
关于BAP1改变的恶性胸膜间皮瘤（MPM）的系统治疗结果，目前所知甚少。
45例MPM患者[组A：从四个以色列癌症中心（ICC）的电子数据库中选出8例发生BAP1失活突变/拷贝数缺失的MPM患者（FoundationOne CDx/TEMPUSxT）；组B：从两个ICC的电子数据库中选出37例连续的（2016 - 2018年）MPM患者，其中6例无BAP1改变（B1组），31例未检测BAP1（B2组）]，分析其一线铂类/培美曲塞±抗血管生成药物（CT，n = 28）、免疫检查点抑制剂（ICPi，n = 16）和聚（ADP - 核糖）聚合酶抑制剂（PARPi，n = 4）治疗的客观缓解率（ORR）、无进展生存期（mRECIST）和总生存期（OS）。评估自诊断以来的总生存期（OSDx）。
各组间CT治疗的ORR或mPFS无差异：组A、B、B1和B2的ORR分别为50%、47%、50%、47%（p>0.9），mPFS分别为9.1个月（95%CI，1.2 - 16.1）、9.2个月（95%CI，2.9 - 13.3）、7.2个月（95%CI，2.3 - NR）、10.9个月（95%CI，2.9 - 20.3）（p>0.8）。各组间ICPi治疗的ORR或mPFS无差异：组A、B、B1和B2的ORR分别为0%、27%、33%、25%（p>0.2），mPFS分别为2.5个月（95%CI，1.4 - 3.7）、3.0个月（95%CI，1.3 - 10.5）、2.0个月（95%CI，1.9 - NR）、4.5个月（95%CI，0.3 - 10.5）（p>0.3）。在组A中，PARPi治疗未观察到缓解；PARPi治疗的mPFS为1.8个月（95%CI，1.8 - NR）。组A、B、B1和B2的OSDx分别为98.3个月（95%CI，9.7 - 98.3）、19.4个月（95%CI，9.7 - 47.3）、18.8个月（95%CI，8.5 - NR）、19.5个月（95%CI，8.3 - 82.2）（p>0.3）。
与未选择的MPM相比，BAP1改变的MPM的特点是CT和ICPi疗效相似。BAP1改变的MPM在数值上较长的OS可能反映了良好的肿瘤生物学特性。PARPi治疗未观察到缓解。
