Department of General Medical Oncology, University Hospitals Leuven and Department of Oncology, KU Leuven, Leuven, Belgium.
European Organization for Research and Treatment of Cancer (EORTC) - Headquarters, Brussels, Belgium.
Breast. 2022 Aug;64:100-111. doi: 10.1016/j.breast.2022.05.004. Epub 2022 May 20.
Older patients are at higher risk of chemotherapy-induced toxicity, raising interest in less toxic anti-HER2 regimens for older persons with HER2-positive (HER2+) metastatic breast cancer (MBC).
This phase II study randomized (1:1) patients with HER2+ MBC, aged 70+ or frail 60+, to first line chemotherapy with metronomic oral cyclophosphamide (M) + Trastuzumab (T) and Pertuzumab (P) or TP alone. T-DM1 was offered in case of progression.
In total, 39 and 41 patients were randomized to TP and TPM arm respectively. Median follow-up is 54.0 months. 24-month PFS was 18.7% (95% CI 8.2-32.4) and 28.7% (95% CI 15.8-43.0), respectively. A total of 49 (61.3%) patients died of whom 37 (75.5%) from disease progression; number of deaths per arm was 27 (69.2%) for TP and 22 (53.7%) for TPM. There was no significant difference in OS between the two arms (median OS TP vs TPM: 32.1 vs 37.5 months, p 0.25). Among the 40 patients who have started T-DM1 after disease progression on TP/TPM, PFS rate at 6 months after start of T-DM1 was 43.6% (95% CI: 27.7-58.5) and grade 3 or higher AE occurred in 18 pts (45%).
Metronomic chemotherapy-based dual blockade (TPM), followed by T-DM1 after progression, provides an active and relatively well tolerated treatment option in an older/frail HER2+ MBC population, with a median survival of over 3 years. Nevertheless, the majority of this older/frail population died from breast cancer, highlighting the need for well tolerated and efficacious treatments in these patients.
老年患者发生化疗诱导毒性的风险更高，这引起了人们对毒性较低的抗 HER2 方案的兴趣，以便为 HER2 阳性（HER2+）转移性乳腺癌（MBC）的老年患者和体弱患者提供治疗。
这项 II 期研究将 HER2+MBC 且年龄 70 岁及以上或体弱 60 岁及以上的患者按 1:1 随机分为一线化疗组（接受环磷酰胺（M）+曲妥珠单抗（T）+帕妥珠单抗（P）的口服节拍化疗，MTP）或单独 TP 组。如果疾病进展，则给予 T-DM1。
共有 39 名和 41 名患者分别被随机分配至 TP 和 TPM 组。中位随访时间为 54.0 个月。24 个月时的 PFS 分别为 18.7%（95%CI 8.2-32.4）和 28.7%（95%CI 15.8-43.0）。共有 49 名（61.3%）患者死于乳腺癌，其中 37 名（75.5%）死于疾病进展；各治疗组的死亡人数分别为 27 名（69.2%）和 22 名（53.7%）。两组之间的 OS 无显著差异（TP 组和 TPM 组的中位 OS 分别为 32.1 个月和 37.5 个月，p=0.25）。在 40 名因 TP/TPM 进展而开始使用 T-DM1 的患者中，T-DM1 开始后 6 个月时的 PFS 率为 43.6%（95%CI：27.7-58.5），18 名患者（45%）发生 3 级或更高级别的 AE。
节拍化疗为基础的双阻断（TPM），在进展后再使用 T-DM1，为老年/体弱 HER2+MBC 患者提供了一种有效且相对耐受良好的治疗选择，中位生存期超过 3 年。然而，该老年/体弱患者群体中的大多数仍死于乳腺癌，这突显了需要为这些患者提供耐受良好且有效的治疗方法。
