Asahina Hajime, Tanaka Kentaro, Morita Satoshi, Maemondo Makoto, Seike Masahiro, Okamoto Isamu, Oizumi Satoshi, Kagamu Hiroshi, Takahashi Kazuhisa, Kikuchi Toshiaki, Isobe Takeshi, Sugio Kenji, Kobayashi Kunihiko
Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Clin Lung Cancer. 2021 Mar;22(2):147-151. doi: 10.1016/j.cllc.2020.09.023. Epub 2020 Oct 16.
Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is now a standard treatment of previously untreated EGFR-mutated advanced non-small-cell lung cancer (NSCLC). However, disease progression occurs within 19 months of treatment. In the NEJ009 study, gefitinib plus carboplatin plus pemetrexed demonstrated significantly better progression-free and overall survival compared with gefitinib monotherapy. Furthermore, the Lung Oncology Group in Kyushu and North East Japan Study Group, major clinical trial groups in Japan, conducted a randomized phase II study to evaluate the efficacy and safety of second-line osimertinib plus carboplatin plus pemetrexed versus osimertinib monotherapy for patients with disease progression during first-line EGFR tyrosine kinase inhibitor therapy and the EGFR T790M resistance mutation (TAKUMI trial; trial registration no., jRCTs071180062). In the first treatment course for the initial 24 patients, no safety issues were reported in the combination arm. Thus, we have planned this phase II study to evaluate the safety and preliminary efficacy of osimertinib plus cisplatin/carboplatin plus pemetrexed therapy for patients with previously untreated EGFR-mutated NSCLC.
A total of 66 patients will be enrolled, because this sample size will be adequate for assessing treatment safety and efficacy. The co-primary endpoints include safety and the objective response rate, and the secondary endpoints include the complete response rate, disease control rate, and progression-free survival.
This is the first study to explore the efficacy and safety of osimertinib combined with platinum-based chemotherapy in previously untreated NSCLC patients with EGFR-sensitizing mutations. Our findings could provide valuable information for phase III studies such as FLAURA2 and for developing treatment strategies for EGFR-mutated NSCLC.
奥希替尼是一种第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，目前是既往未经治疗的EGFR突变型晚期非小细胞肺癌（NSCLC）的标准治疗方法。然而，疾病进展发生在治疗的19个月内。在NEJ009研究中，吉非替尼联合卡铂和培美曲塞与吉非替尼单药治疗相比，显示出显著更好的无进展生存期和总生存期。此外，日本主要的临床试验组九州肺癌研究组和日本东北肺癌研究组进行了一项随机II期研究，以评估二线奥希替尼联合卡铂和培美曲塞与奥希替尼单药治疗对一线EGFR酪氨酸激酶抑制剂治疗期间疾病进展且具有EGFR T790M耐药突变患者的疗效和安全性（TAKUMI试验；试验注册号，jRCTs071180062）。在最初24例患者的第一个治疗疗程中，联合治疗组未报告安全问题。因此，我们计划开展这项II期研究，以评估奥希替尼联合顺铂/卡铂和培美曲塞治疗既往未经治疗的EGFR突变型NSCLC患者的安全性和初步疗效。
总共将纳入66例患者，因为这个样本量足以评估治疗的安全性和疗效。共同主要终点包括安全性和客观缓解率，次要终点包括完全缓解率、疾病控制率和无进展生存期。
这是第一项探索奥希替尼联合铂类化疗在既往未经治疗的具有EGFR敏感突变的NSCLC患者中的疗效和安全性的研究。我们的研究结果可为FLAURA2等III期研究以及制定EGFR突变型NSCLC的治疗策略提供有价值的信息。
