Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
E-A Biostatistical Center, Boston, MA.
JCO Precis Oncol. 2022 Jul;6:e2200165. doi: 10.1200/PO.22.00165.
National Cancer Institute-Molecular Analysis for Therapy Choice is a multicohort trial that assigns patients with advanced cancers to targeted therapies on the basis of central tumor genomic testing. Arm B evaluated afatinib, an ErbB family tyrosine kinase inhibitor, in patients with -activating mutations.
Eligible patients had selected single-nucleotide variants or insertions/deletions detected by the National Cancer Institute-Molecular Analysis for Therapy Choice next-generation sequencing assay. Patients had performance status ≤ 1, left ventricular ejection fraction > 50%, grade ≤ 1 diarrhea, and no prior human epidermal growth factor receptor 2 (HER2) therapy. Patients received afatinib 40 mg once daily in 28-day cycles. The primary end point was objective response rate (ORR). Secondary end points were 6-month progression-free survival, overall survival, toxicity, and molecular correlates.
A total of 59 patients were assigned and 40 were enrolled. The median age was 62 years, 78% were female, 68% had performance status = 1, and 58% had received > 3 prior therapies. The confirmed ORR was 2.7% (n = 1 of 37; 90% CI, 0.14 to 12.2), and 6-month progression-free survival was 12.0% (90% CI, 5.6 to 25.8). A confirmed partial response occurred in a patient with adenocarcinoma of extra-mammary Paget disease of skin who progressed after cycle 6. Two unconfirmed partial responses were observed (low-grade serous gynecological tract and estrogen receptor-positive/HER2-negative immunohistochemistry breast ductal carcinoma). Of 12 patients with breast cancer, 1 additional patient with lobular carcinoma (estrogen receptor-positive/HER2 fluorescent in situ hybridization) had a 51% reduction in target lesions but progressed because of a new lesion at cycle 6. The most common (> 20%) treatment-related adverse events were diarrhea (68%), mucositis (43%), fatigue (40%), acneiform rash (30%), dehydration (27%), vomiting (27%), nausea (27%), anemia (27%), and anorexia (22%). Four patients (11%) discontinued because of adverse events.
Although afatinib did not meet the prespecified threshold for antitumor activity in this heavily pretreated cohort, the response in a rare tumor type is notable. The safety profile of afatinib was consistent with prior studies.
美国国家癌症研究所-分子分析治疗选择是一项多队列试验，根据中心肿瘤基因组检测为晚期癌症患者分配靶向治疗。臂 B 评估了 afatinib，一种 ErbB 家族酪氨酸激酶抑制剂，用于治疗 -激活突变的患者。
符合条件的患者具有通过美国国家癌症研究所-分子分析治疗选择下一代测序检测到的选定单核苷酸变异或插入/缺失。患者的表现状态≤1，左心室射血分数> 50％，腹泻等级≤1，并且没有先前的人表皮生长因子受体 2（HER2）治疗。患者以 40 mg 每天一次的剂量接受 afatinib 治疗，为期 28 天的周期。主要终点是客观缓解率（ORR）。次要终点是 6 个月无进展生存期，总生存期，毒性和分子相关性。
共分配了 59 名患者，其中 40 名入组。中位年龄为 62 岁，78％为女性，68％的表现状态= 1，58％的患者接受了> 3 种先前的治疗。确认的 ORR 为 2.7％（n = 37 中的 1 例；90％CI，0.14 至 12.2），6 个月无进展生存率为 12.0％（90％CI，5.6 至 25.8）。一名患有皮肤外乳腺派杰病腺癌的患者在第 6 周期后进展，确认出现部分缓解。观察到 2 例未确认的部分缓解（低级别浆液性妇科生殖道和雌激素受体阳性/HER2 免疫组化乳腺导管癌）。在 12 名乳腺癌患者中，另一名患有小叶癌（雌激素受体阳性/HER2 荧光原位杂交）的患者靶病变减少了 51％，但由于第 6 周期时出现新病变而进展。最常见（> 20％）的与治疗相关的不良事件是腹泻（68％），粘膜炎（43％），疲劳（40％），痤疮样皮疹（30％），脱水（27％），呕吐（27％），恶心（27％），贫血（27％）和厌食（22％）。由于不良事件，有 4 名患者（11％）停止治疗。
尽管 afatinib 在这种预处理的患者中未达到抗肿瘤活性的规定阈值，但在罕见肿瘤类型中的反应值得注意。 afatinib 的安全性与先前的研究一致。
