National Cancer Center Hospital East, Kashiwa, Japan.
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Nat Commun. 2023 Jun 7;14(1):3332. doi: 10.1038/s41467-023-38032-4.
DESTINY-CRC01 (NCT03384940) was a multicenter, open-label, phase 2 trial assessing the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with HER2-expressing metastatic colorectal cancer (mCRC) that progressed after ≥2 prior regimens; results of the primary analysis are published. Patients received T-DXd 6.4 mg/kg every 3 weeks and were assigned to either: cohort A (HER2-positive, immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+), cohort B (IHC 2+/ISH-), or cohort C (IHC 1+). Primary endpoint was objective response rate (ORR) by independent central review in cohort A. Secondary endpoints included ORR (cohorts B and C), duration of response, disease control rate, progression-free survival, overall survival, pharmacokinetics, and safety of T-DXd. 86 patients were enrolled (53 in cohort A, 15 in cohort B, and 18 in cohort C). Results of the primary analysis are published, reporting an ORR of 45.3% in cohort A. Here, we report the final results. No responses occurred in cohorts B or C. Median progression-free survival, overall survival, and duration of response were 6.9, 15.5, and 7.0 months, respectively. Overall serum exposure (cycle 1) of T-DXd, total anti-HER2 antibody, and DXd were similar regardless of HER2 status. Most common grade ≥3 treatment-emergent adverse events were decreased neutrophil count and anemia. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 8 patients (9.3%). These findings support the continued exploration of T-DXd in HER2-positive mCRC.
DESTINY-CRC01（NCT03384940）是一项多中心、开放标签、2 期临床试验，评估了曲妥珠单抗-德鲁替康（T-DXd）在既往接受≥2 种方案治疗后进展的 HER2 表达转移性结直肠癌（mCRC）患者中的疗效和安全性；主要分析结果已发表。患者接受 6.4mg/kg 的 T-DXd 每 3 周一次，并被分配到以下三个队列之一：队列 A（HER2 阳性，免疫组化[IHC] 3+或 IHC 2+/原位杂交[ISH]+），队列 B（IHC 2+/ISH-）或队列 C（IHC 1+）。主要终点是独立中心评估在队列 A 中的客观缓解率（ORR）。次要终点包括队列 B 和 C 的 ORR、缓解持续时间、疾病控制率、无进展生存期、总生存期、T-DXd 的药代动力学和安全性。共纳入 86 例患者（队列 A 53 例，队列 B 15 例，队列 C 18 例）。主要分析结果已发表，报告队列 A 的 ORR 为 45.3%。在此，我们报告最终结果。队列 B 和 C 均未出现缓解。中位无进展生存期、总生存期和缓解持续时间分别为 6.9、15.5 和 7.0 个月。无论 HER2 状态如何，T-DXd、总抗 HER2 抗体和 DXd 的总体血清暴露（第 1 周期）均相似。最常见的≥3 级治疗相关不良事件是中性粒细胞计数减少和贫血。8 例患者（9.3%）发生药物相关性间质性肺病/肺炎。这些发现支持继续探索 T-DXd 在 HER2 阳性 mCRC 中的应用。
