Department of Medical Oncology, Institut de Cancerologie de l'Ouest, Saint-Herblain, France.
Department of Medical Oncology, Gustave Roussy Cancer Center, Villejuif, France.
JAMA Netw Open. 2024 Apr 1;7(4):e244435. doi: 10.1001/jamanetworkopen.2024.4435.
Little is known regarding the outcomes associated with tucatinib combined with trastuzumab and capecitabine (TTC) after trastuzumab-deruxtecan exposure among patients with ERBB2 (previously HER2)-positive metastatic breast cancer (MBC).
To investigate outcomes following TTC treatment in patients with ERBB2-positive MBC who had previously received trastuzumab-deruxtecan.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study included all patients with MBC who were treated in 12 French comprehensive cancer centers between August 1, 2020, and December 31, 2022.
Tucatinib combined with trastuzumab and capecitabine administered at the recommended dose.
Clinical end points included progression-free survival (PFS), time to next treatment (TTNT), overall survival (OS), and overall response rate (ORR).
A total of 101 patients with MBC were included (median age, 56 [range, 31-85] years). The median number of prior treatment lines for metastatic disease at TTC treatment initiation was 4 (range, 2-15), including 82 patients (81.2%) with previous trastuzumab and/or pertuzumab and 94 (93.1%) with previous ado-trastuzumab-emtansine) exposure. The median duration of trastuzumab-deruxtecan treatment was 8.9 (range, 1.4-25.8) months, and 82 patients (81.2%) had disease progression during trastuzumab-deruxtecan treatment, whereas 18 (17.8%) had stopped trastuzumab-deruxtecan for toxic effects and 1 (1.0%) for other reasons. Tucatinib combined with trastuzumab and capecitabine was provided as a third- or fourth-line treatment in 37 patients (36.6%) and was the immediate treatment after trastuzumab-deruxtecan in 86 (85.1%). With a median follow-up of 11.6 (95% CI, 10.5-13.4) months, 76 of 101 patients (75.2%) stopped TTC treatment due to disease progression. The median PFS was 4.7 (95% CI, 3.9-5.6) months; median TTNT, 5.2 (95% CI, 4.5-7.0) months; and median OS, 13.4 (95% CI, 11.1 to not reached [NR]) months. Patients who received TTC immediately after trastuzumab-deruxtecan had a median PFS of 5.0 (95% CI, 4.2-6.0) months; median TTNT of 5.5 (95% CI, 4.8-7.2) months, and median OS of 13.4 (95% CI, 11.9-NR) months. Those who received TTC due to trastuzumab-deruxtecan toxicity-related discontinuation had a median PFS of 7.3 (95% CI, 3.0-NR) months. Best ORR was 29 of 89 patients (32.6%). Sixteen patients with active brain metastasis had a median PFS of 4.7 (95% CI, 3.0-7.3) months, median TTNT of 5.6 (95% CI, 4.4 to NR), and median OS of 12.4 (95% CI, 8.3-NR) months.
In this study, TTC therapy was associated with clinically meaningful outcomes in patients with ERBB2-positive MBC after previous trastuzumab-deruxtecan treatment, including those with brain metastases. Prospective data on optimal drug sequencing in this rapidly changing therapeutic landscape are needed.
在接受曲妥珠单抗 - 德曲妥珠单抗治疗后，接受曲妥珠单抗 - 德曲妥珠单抗治疗的 ERBB2（以前称为 HER2）阳性转移性乳腺癌（MBC）患者联合使用曲妥珠单抗、卡培他滨和 Tucatinib（TTC）的相关结局知之甚少。
调查先前接受过曲妥珠单抗 - 德曲妥珠单抗治疗的 ERBB2 阳性 MBC 患者接受 TTC 治疗后的结局。
设计、设置和参与者：这项队列研究纳入了 2020 年 8 月 1 日至 2022 年 12 月 31 日期间在 12 家法国综合癌症中心接受治疗的所有 MBC 患者。
推荐剂量的 Tucatinib 联合曲妥珠单抗和卡培他滨。
临床终点包括无进展生存期（PFS）、至下一治疗时间（TTNT）、总生存期（OS）和总缓解率（ORR）。
共纳入 101 例 MBC 患者（中位年龄 56 岁[范围 31-85 岁]）。TTC 治疗开始时转移性疾病的先前治疗线中位数为 4 条（范围 2-15 条），包括 82 例（81.2%）患者既往接受过曲妥珠单抗和/或培妥珠单抗治疗，94 例（93.1%）患者既往接受过 ado-trastuzumab-emtansine）治疗。曲妥珠单抗 - 德曲妥珠单抗治疗的中位持续时间为 8.9 个月（范围 1.4-25.8 个月），82 例患者（81.2%）在曲妥珠单抗 - 德曲妥珠单抗治疗期间疾病进展，而 18 例（17.8%）因毒性而停止曲妥珠单抗 - 德曲妥珠单抗治疗，1 例（1.0%）因其他原因停止治疗。37 例（36.6%）患者将 Tucatinib 联合曲妥珠单抗和卡培他滨作为三线或四线治疗，86 例（85.1%）患者在曲妥珠单抗 - 德曲妥珠单抗治疗后立即接受治疗。中位随访 11.6 个月（95%CI，10.5-13.4），101 例患者中有 76 例（75.2%）因疾病进展而停止 TTC 治疗。中位 PFS 为 4.7 个月（95%CI，3.9-5.6 个月）；中位 TTNT 为 5.2 个月（95%CI，4.5-7.0 个月）；中位 OS 为 13.4 个月（95%CI，11.1-NR）。立即接受曲妥珠单抗 - 德曲妥珠单抗治疗后接受 TTC 治疗的患者中位 PFS 为 5.0 个月（95%CI，4.2-6.0 个月）；中位 TTNT 为 5.5 个月（95%CI，4.8-7.2 个月），中位 OS 为 13.4 个月（95%CI，11.9-NR）。因曲妥珠单抗 - 德曲妥珠单抗相关毒性而停药接受 TTC 治疗的患者中位 PFS 为 7.3 个月（95%CI，3.0-NR）。最佳 ORR 为 89 例患者中的 29 例（32.6%）。16 例有活动性脑转移的患者中位 PFS 为 4.7 个月（95%CI，3.0-7.3 个月），中位 TTNT 为 5.6 个月（95%CI，4.4-NR），中位 OS 为 12.4 个月（95%CI，8.3-NR）。
在这项研究中，在先前接受过曲妥珠单抗 - 德曲妥珠单抗治疗的 ERBB2 阳性 MBC 患者中，TTC 治疗与包括脑转移患者在内的临床相关结局相关。在这一快速变化的治疗领域，需要前瞻性数据来确定最佳药物序贯治疗。
