Iwama Eiji, Zenke Yoshitaka, Sugawara Shunichi, Daga Haruko, Morise Masahiro, Yanagitani Noriko, Sakamoto Tomohiro, Murakami Haruyasu, Kishimoto Junji, Matsumoto Shingo, Nakanishi Yoichi, Goto Koichi, Okamoto Isamu
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Eur J Cancer. 2022 Feb;162:99-106. doi: 10.1016/j.ejca.2021.11.021. Epub 2021 Dec 24.
Human epidermal growth factor receptor 2 (HER2) mutations are present in ∼3% of patients with non-small cell lung cancer (NSCLC), with exon-20 insertions accounting for ∼90% of such HER2 mutations and having been identified as driver oncogenic alterations. Antibody-cytotoxic drug conjugates including trastuzumab deruxtecan have shown an excellent efficacy for NSCLC with HER2 mutations. We have now performed a phase II study to evaluate the efficacy of ado-trastuzumab emtansine (T-DM1) for NSCLC positive for HER2 exon-20 insertion mutations.
Eligible patients with HER2 exon-20 insertion mutations confirmed by next-generation sequencing or multiplex polymerase chain reaction platforms and a history of one or two lines of chemotherapy received T-DM1 (3.6 mg/kg) intravenously every 21 days. The primary end-point of the study was the objective response rate (ORR).
Between February 2019 and July 2020, 22 patients were enrolled in the study. A775_G776insYVMA was the most frequent HER2 exon-20 insertion mutation, accounting for 19 (86.4%) of the 22 patients. The ORR was 38.1% (90% confidence interval, 23.0-55.9%), and the disease control rate was 52.4%. The median duration of response was 3.5 months, and the median progression-free survival and median overall survival were 2.8 and 8.1 months, respectively. Toxicity was mild, with the frequency of adverse events of grade ≥3 being low.
T-DM1 is a potential treatment option for patients with NSCLC with HER2 exon-20 insertion mutations. Further investigation of biomarkers for T-DM1 is warranted to improve its efficacy for NSCLC with such mutations.
JapicCTI-194620.
人表皮生长因子受体2（HER2）突变存在于约3%的非小细胞肺癌（NSCLC）患者中，其中外显子20插入约占此类HER2突变的90%，并已被确定为驱动致癌改变。包括曲妥珠单抗德卢替康在内的抗体-细胞毒性药物偶联物已显示出对HER2突变的NSCLC具有优异疗效。我们现在进行了一项II期研究，以评估ado-曲妥珠单抗恩美曲妥珠单抗（T-DM1）对HER2外显子20插入突变阳性的NSCLC的疗效。
经下一代测序或多重聚合酶链反应平台确认存在HER2外显子20插入突变且有一或二线化疗史的合格患者，每21天静脉注射一次T-DM1（3.6mg/kg）。该研究的主要终点是客观缓解率（ORR）。
2019年2月至2020年7月期间，22例患者入组该研究。A775_G776insYVMA是最常见的HER2外显子20插入突变，占22例患者中的19例（86.4%）。ORR为38.1%（90%置信区间，23.0-55.9%），疾病控制率为52.4%。中位缓解持续时间为3.5个月，中位无进展生存期和中位总生存期分别为2.8个月和8.1个月。毒性较轻，≥3级不良事件的发生率较低。
T-DM1是HER2外显子20插入突变的NSCLC患者的一种潜在治疗选择。有必要进一步研究T-DM1的生物标志物，以提高其对此类突变NSCLC的疗效。
JapicCTI-194620。
