Sakaeda Mariko, Kotani Naoki, Yoneya Takaaki, Zheng Yue, Habara Yuji
CHUGAI PHARMACEUTICAL CO., LTD.
Nihon Yakurigaku Zasshi. 2024;159(4):241-253. doi: 10.1254/fpj.24022.
Pertuzumab and trastuzumab are anti-HER2 humanized monoclonal antibodies with different mechanisms of action. Their combination is expected to suppress intracellular HER2 signaling additively or synergistically. Their combination is widely recommended worldwide and has been established as a standard of care for HER2-positive breast cancer. However, improvement is required because of the prolonged time of intravenous infusion. Vorhyaluronidase alfa (rHuPH20) depolymerizes hyaluronan in the subcutaneous connective tissue. It's reported to increase the permeability and absorption levels of drugs. PHESGO combination for subcutaneous injection MA/IN (PHESGO) is a fixed-dose combination of pertuzumab, trastuzumab, and rHuPH20. A confirmatory phase III study (FeDeriCa) was conducted following a dose-finding phase I study (BO30185). Patients with HER2-positive early breast cancer were randomly assigned to receive either intravenous infusion of pertuzumab and trastuzumab or subcutaneous injection of PHESGO, in combination with chemotherapy, to compare the pharmacokinetics (PK), efficacy and safety. A phase II study (PHranceSCa) was also conducted to assess patients' preference and satisfaction. Based on these results, population PK analysis, and other data, PHESGO obtained marketing approval in Japan in September 2023 with indications for "HER2-positive breast cancer" and "advanced or recurrent HER2-positive colorectal cancer that has progressed following cancer chemotherapy and is not amenable to curative resection". By reducing the administration time, PHESGO is expected to contribute to various needs of patients and improvement of their daily lives. Since drug preparation is not required, it can provide convenience to healthcare professionals, leading to stress reduction of medical resources as well.
帕妥珠单抗和曲妥珠单抗是作用机制不同的抗HER2人源化单克隆抗体。它们的联合使用有望相加或协同抑制细胞内HER2信号传导。它们的联合使用在全球范围内得到广泛推荐，并已成为HER2阳性乳腺癌的护理标准。然而，由于静脉输注时间较长，仍需要改进。透明质酸酶α（rHuPH20）可使皮下结缔组织中的透明质酸解聚。据报道，它能提高药物的通透性和吸收水平。皮下注射用帕妥珠单抗、曲妥珠单抗和透明质酸酶α固定剂量组合（PHESGO）是帕妥珠单抗、曲妥珠单抗和rHuPH20的固定剂量组合。在剂量探索性I期研究（BO30185）之后进行了一项验证性III期研究（FeDeriCa）。HER2阳性早期乳腺癌患者被随机分配接受帕妥珠单抗和曲妥珠单抗静脉输注或皮下注射PHESGO，并联合化疗，以比较药代动力学（PK）、疗效和安全性。还进行了一项II期研究（PHranceSCa）以评估患者的偏好和满意度。基于这些结果、群体PK分析和其他数据，PHESGO于2023年9月在日本获得上市批准，适应症为“HER2阳性乳腺癌”和“癌症化疗后进展且无法进行根治性切除的晚期或复发性HER2阳性结直肠癌”。通过减少给药时间，PHESGO有望满足患者的各种需求并改善他们的日常生活。由于无需药物配制，它可以为医护人员提供便利，也能减轻医疗资源的压力。
