Abstract:
Trastuzumab, a key treatment for HER2-positive breast cancer, is available in weight-based IV and fixed-dose (600 mg) SC formulations. While the Phase 3 HannaH trial indicated non-inferiority of the SC formulation, there is some concern that the target plasma concentration may not be reached in overweight/obese patients whereas low-body-weight patients may be at risk of toxicity. This scoping review evaluated whether overweight/obese patients are at risk of below-target exposure with fixed-dose SC trastuzumab, whether low-body-weight patients are at risk of increased toxicity, especially cardiotoxicity, and whether IV and SC trastuzumab are equivalent in terms of treatment-emergent adverse events (TEAEs) (e.g. infections). Thirty-seven publications that met the eligibility criteria were included. Body weight is not an important determinant of exposure to trastuzumab at steady state (i.e. pre-dose cycle 8); however, real-world evidence suggests that the target concentration (20 μg/mL) may not be reached with the first SC dose in overweight/obese patients. There is no evidence that low-body-weight patients are at increased risk of cardiotoxicity with SC trastuzumab, although this may be confounded by the higher rate of cardiovascular comorbidities in overweight patients. In Phase 3 trials, SC trastuzumab was associated with higher rates of ISRs, ADAs and SAEs, the latter often requiring hospitalization and occurring during adjuvant treatment when patients are not burdened by chemotherapy. The route of administration of trastuzumab (IV vs SC) in different treatment settings should be discussed with the patient, taking into account the risks and benefits associated with each route.
摘要:
曲妥珠单抗,HER2阳性乳腺癌的关键治疗方法,可用于基于重量的IV和固定剂量(600mg)SC制剂。虽然3期HannaH试验表明SC制剂具有非劣效性,有人担心超重/肥胖患者可能无法达到目标血浆浓度,而低体重患者可能存在毒性反应的风险.这项范围审查评估了超重/肥胖患者是否存在固定剂量SC曲妥珠单抗低于目标暴露的风险,低体重患者是否有毒性增加的风险,尤其是心脏毒性,以及IV和SC曲妥珠单抗在治疗引起的不良事件(TEAE)(例如感染)方面是否相同。纳入了符合资格标准的37份出版物。体重不是在稳定状态下(即剂量前周期8)暴露于曲妥珠单抗的重要决定因素;然而,现实世界的证据表明,超重/肥胖患者的首次SC剂量可能无法达到目标浓度(20μg/mL).没有证据表明低体重患者服用SC曲妥珠单抗会增加心脏毒性的风险,尽管这可能与超重患者心血管合并症发生率较高有关。在第三阶段试验中,SC曲妥珠单抗与更高的ISR发生率相关,ADA和SAE,后者通常需要住院治疗,并且在辅助治疗期间发生,而患者没有化疗负担。应与患者讨论曲妥珠单抗在不同治疗环境中的给药途径(IVvsSC),考虑到与每条路线相关的风险和收益。