Department of Respiratory Medicine and Hematology, Hyogo Medical University, Hyogo, Japan;
Oncology Clinical Operation II, ONO Pharmaceutical Co., LTD., Osaka, Japan.
Anticancer Res. 2024 Oct;44(10):4135-4145. doi: 10.21873/anticanres.17244.
In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs.
2004 年 2 月，美国食品和药物管理局（FDA）率先批准顺铂（CDDP）和培美曲塞（PEM）联合用于未经治疗、不可切除的恶性胸膜间皮瘤（MPM）的标准一线化疗。然而，在那次批准之后，将近 15 年来，MPM 的标准一线治疗在没有取得任何进展。2015 年 12 月，《柳叶刀》杂志发表了一项 3 期研究（间皮瘤贝伐单抗顺铂培美曲塞研究：MAPS）的阳性结果，证实了抗血管生成药物贝伐单抗联合 CDDP/PEM 用于不可切除的 MPM 的疗效；然而，这并没有导致国家药物监管机构的批准。此外，对于对 CDDP/PEM 耐药的病例，没有建立二线治疗。2018 年 8 月，日本药品和医疗器械管理局成为世界上第一个批准免疫检查点抑制剂（ICI）nivolumab 单药治疗先前不可切除、晚期或复发性 MPM 的机构。继日本之后，2020 年 10 月，FDA 批准 nivolumab 和 ipilimumab 联合用于治疗未经治疗的不可切除 MPM。在本文中，我们根据历史背景，重点介绍 ICI 的益处，回顾 MPM 药物治疗的转变。
