Abstract：
OBJECTIVE: National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) was a multicohort phase 2 trial that assigned patients with advanced pretreated cancers to molecularly targeted therapies on the basis of tumor genomic testing. NCI-MATCH Arm A evaluated afatinib, an EGFR tyrosine kinase inhibitor (TKI) approved for advanced non-small cell lung cancer, in patients with tumors other than lung cancer harboring EGFR mutations.
METHODS: Patients with advanced pretreated cancers other than lung cancer found to have selected actionable EGFR mutations were offered participation in Arm A. Previous therapy with an EGFR TKI was not allowed. Patients received afatinib 40 mg once daily continuously until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), 6-month PFS, and overall survival (OS).
RESULTS: Seventeen patients received protocol therapy. Tumor types included glioblastoma multiforme (GBM) (13), gliosarcoma (1), adenocarcinoma not otherwise specified (NOS) (2), and adenosquamous carcinoma of the breast (1). Fifty-nine percent of patients received ≥2 lines of previous therapy. The ORR was 11.8% (90% CI, 2.1 to 32.6), with one complete response lasting 16.4 months (GBM harboring a rare exon 18 EGFR-SEPT14 fusion) and one partial response lasting 12.8 months (adenocarcinoma NOS with the classic EGFR mutation, p.Glu746_Ala750del). Three patients had stable disease. The 6-month PFS was 15% (90% CI, 0 to 30.7); the median OS was 9 months (90% CI, 4.6 to 14.0). Rash and diarrhea were the most common toxicities.
CONCLUSIONS: Afatinib had modest activity in a cohort of patients with heavily pretreated cancer with advanced nonlung, EGFR-mutated tumors, but the trial\'s primary end point was not met. Further evaluation of afatinib in GBM with EGFR exon 18 fusions may be of interest.
METHODS: Patients with advanced pretreated cancers other than lung cancer found to have selected actionable EGFR mutations were offered participation in Arm A. Previous therapy with an EGFR TKI was not allowed. Patients received afatinib 40 mg once daily continuously until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), 6-month PFS, and overall survival (OS).
RESULTS: Seventeen patients received protocol therapy. Tumor types included glioblastoma multiforme (GBM) (13), gliosarcoma (1), adenocarcinoma not otherwise specified (NOS) (2), and adenosquamous carcinoma of the breast (1). Fifty-nine percent of patients received ≥2 lines of previous therapy. The ORR was 11.8% (90% CI, 2.1 to 32.6), with one complete response lasting 16.4 months (GBM harboring a rare exon 18 EGFR-SEPT14 fusion) and one partial response lasting 12.8 months (adenocarcinoma NOS with the classic EGFR mutation, p.Glu746_Ala750del). Three patients had stable disease. The 6-month PFS was 15% (90% CI, 0 to 30.7); the median OS was 9 months (90% CI, 4.6 to 14.0). Rash and diarrhea were the most common toxicities.
CONCLUSIONS: Afatinib had modest activity in a cohort of patients with heavily pretreated cancer with advanced nonlung, EGFR-mutated tumors, but the trial\'s primary end point was not met. Further evaluation of afatinib in GBM with EGFR exon 18 fusions may be of interest.
摘要：
目的：美国国家癌症研究所-分子分析治疗选择（NCI-MATCH）是一项多队列2期试验，根据肿瘤基因组测试，将晚期预处理癌症患者分配到分子靶向治疗。NCI-MATCHA组评估了阿法替尼，EGFR酪氨酸激酶抑制剂（TKI）被批准用于晚期非小细胞肺癌，在具有EGFR突变的肺癌以外的肿瘤患者中。
方法：除肺癌以外的晚期预处理癌症患者被发现具有选择的可行EGFR突变，可参与A组。以前使用EGFRTKI治疗是不允许的。患者接受阿法替尼40mg，每天一次，持续直至疾病进展或不可接受的毒性。主要终点是客观缓解率(ORR)。次要终点包括无进展生存期（PFS），6个月PFS,总生存率（OS）。
结果：17例患者接受了方案治疗。肿瘤类型包括多形性胶质母细胞瘤（GBM）（13），胶质肉瘤(1),未另作说明的腺癌（NOS）（2），和乳腺腺鳞癌（1）。59％的患者接受了≥2行先前治疗。ORR为11.8%（90%CI，2.1至32.6），一个持续16.4个月的完全反应（GBM具有罕见的外显子18EGFR-SEPT14融合）和一个持续12.8个月的部分反应（腺癌NOS具有经典的EGFR突变，p.Glu746_Ala750del)。3名患者病情稳定。6个月PFS为15％（90％CI，0至30.7）；中位OS为9个月（90％CI，4.6至14.0）。皮疹和腹泻是最常见的毒性。
结论：阿法替尼在重度预治疗晚期非肺癌患者队列中具有适度的活性，EGFR突变的肿瘤，但未达到试验的主要终点.阿法替尼在具有EGFR外显子18融合的GBM中的进一步评估可能是有意义的。
方法：除肺癌以外的晚期预处理癌症患者被发现具有选择的可行EGFR突变，可参与A组。以前使用EGFRTKI治疗是不允许的。患者接受阿法替尼40mg，每天一次，持续直至疾病进展或不可接受的毒性。主要终点是客观缓解率(ORR)。次要终点包括无进展生存期（PFS），6个月PFS,总生存率（OS）。
结果：17例患者接受了方案治疗。肿瘤类型包括多形性胶质母细胞瘤（GBM）（13），胶质肉瘤(1),未另作说明的腺癌（NOS）（2），和乳腺腺鳞癌（1）。59％的患者接受了≥2行先前治疗。ORR为11.8%（90%CI，2.1至32.6），一个持续16.4个月的完全反应（GBM具有罕见的外显子18EGFR-SEPT14融合）和一个持续12.8个月的部分反应（腺癌NOS具有经典的EGFR突变，p.Glu746_Ala750del)。3名患者病情稳定。6个月PFS为15％（90％CI，0至30.7）；中位OS为9个月（90％CI，4.6至14.0）。皮疹和腹泻是最常见的毒性。
结论：阿法替尼在重度预治疗晚期非肺癌患者队列中具有适度的活性，EGFR突变的肿瘤，但未达到试验的主要终点.阿法替尼在具有EGFR外显子18融合的GBM中的进一步评估可能是有意义的。
