Wang Kaiwen, Du Robyn, Myall Nathaniel J, Lewis Whitney E, Uy Natalie, Hong Lingzhi, Skoulidis Ferdinandos, Byers Lauren A, Tsao Anne, Cascone Tina, Pozadzides Jenny, Tu Janet, Negrao Marcelo V, Gibbons Don L, Park Keunchil, Rinsurongkawong Waree, Lee J Jack, Gandara David, Behl Deepti, Shu Catherine A, Riess Jonathan W, Baik Christina, Wakelee Heather A, Vaporciyan Ara A, Heymach John V, Zhang Jianjun, Le Xiuning
Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
J Thorac Oncol. 2024 Mar;19(3):500-506. doi: 10.1016/j.jtho.2023.11.020. Epub 2023 Nov 25.
Amivantamab-vmjw (amivantamab) is a bispecific EGFR/MET antibody approved for patients with advanced NSCLC with EGFR exon 20 insertion mutations, after prior therapy. Nevertheless, the benefits and safety of amivantamab in other EGFR-mutant lung cancer, with or without osimertinib, and with concurrent radiation therapy, are less known.
We queried the MD Anderson Lung Cancer GEMINI, Fred Hutchinson Cancer Research Center, University of California Davis Comprehensive Cancer Center, and Stanford Cancer Center's database for patients with EGFR-mutant NSCLC treated with amivantamab, not on a clinical trial. The data analyzed included initial response, duration of treatment, and concomitant radiation safety in overall population and prespecified subgroups.
A total of 61 patients received amivantamab. Median age was 65 (31-81) years old; 72.1% were female; and 77% were patients with never smoking history. Median number of prior lines of therapies was four. On the basis of tumor's EGFR mutation, 39 patients were in the classical mutation cohort, 15 patients in the exon 20 cohort, and seven patients in the atypical cohort. There were 37 patients (58.7%) who received amivantamab concomitantly with osimertinib and 25 patients (39.1%) who received concomitant radiation. Furthermore, 54 patients were assessable for response in the overall population; 19 patients (45.2%) had clinical response and disease control rate (DCR) was 64.3%. In the classical mutation cohort of the 33 assessable patients, 12 (36.4%) had clinical response and DCR was 48.5%. In the atypical mutation cohort, six of the seven patients (85.7%) had clinical response and DCR was 100%. Of the 13 assessable patients in the exon 20 cohort, five patients (35.7%) had clinical response and DCR was 64.3%. Adverse events reported with amivantamab use were similar as previously described in product labeling. No additional toxicities were noted when amivantamab was given with radiation with or without osimertinib.
Our real-world multicenter analysis revealed that amivantamab is a potentially effective treatment option for patients with EGFR mutations outside of exon 20 insertion mutations. The combination of osimertinib with amivantamab is safe and feasible. Radiation therapy also seems safe when administered sequentially or concurrently with amivantamab.
氨伏单抗（amivantamab-vmjw，简称amivantamab）是一种双特异性表皮生长因子受体/间质-上皮转化因子（EGFR/MET）抗体，已被批准用于先前接受过治疗的、具有EGFR外显子20插入突变的晚期非小细胞肺癌（NSCLC）患者。然而，对于amivantamab在其他EGFR突变型肺癌中的疗效和安全性，无论是否联合奥希替尼以及是否同时进行放射治疗，人们了解较少。
我们查询了MD安德森癌症中心肺癌GEMINI数据库、弗雷德·哈钦森癌症研究中心数据库、加利福尼亚大学戴维斯分校综合癌症中心数据库以及斯坦福癌症中心数据库，以获取接受amivantamab治疗且未参加临床试验的EGFR突变型NSCLC患者的数据。分析的数据包括总体人群和预先指定亚组中的初始反应、治疗持续时间以及同步放疗安全性。
共有61例患者接受了amivantamab治疗。中位年龄为65岁（31 - 81岁）；72.1%为女性；77%为从不吸烟患者。先前治疗的中位疗程数为4个。根据肿瘤的EGFR突变情况，39例患者属于经典突变队列，15例患者属于外显子20队列，7例患者属于非典型队列。有37例患者（58.7%）同时接受了amivantamab和奥希替尼治疗，25例患者（39.1%）接受了同步放疗。此外，总体人群中有54例患者可评估反应；19例患者（45.2%）有临床反应，疾病控制率（DCR）为64.3%。在33例可评估的经典突变队列患者中，12例（36.4%）有临床反应，DCR为48.5%。在非典型突变队列中，7例患者中有6例（85.7%）有临床反应，DCR为100%。在外显子20队列的13例可评估患者中，5例患者（35.7%）有临床反应，DCR为64.3%。使用amivantamab报告的不良事件与产品标签中先前描述的相似。当amivantamab与放疗联合使用，无论是否联合奥希替尼，均未发现额外的毒性。
我们的真实世界多中心分析表明，对于非外显子20插入突变的EGFR突变患者，amivantamab是一种潜在有效的治疗选择。奥希替尼与amivantamab联合使用安全可行。当与amivantamab序贯或同步使用时，放射治疗似乎也很安全。
