From Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai (C.Z.), the Division of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou (K.-J.T.), and Harbin Medical University Cancer Hospital, Harbin (B.L.) - all in China; the Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine (B.C.C.), Asan Medical Center, University of Ulsan College of Medicine (S. Kim), and Samsung Medical Center, Sungkyunkwan University School of Medicine (K.P.) - all in Seoul, South Korea; Hospital Universitario 12 de Octubre, Madrid (L.P.-A.), and Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (E.F.) and Hospital de la Santa Creu I Sant Pau (M.M.), Barcelona - all in Spain; Sunnybrook Odette Cancer Centre, Toronto (S.C.); Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo (S. Kitazono), and Shizuoka Cancer Center, Shizuoka (A.O.) - both in Japan; General Hospital Kuala Lumpur, Kuala Lumpur, Malaysia (M.T.); David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.W.G.), and Janssen Research and Development, San Diego (S.M.S.) - both in California; NYU Langone Health, New York (J.K.S.); Earle A. Chiles Research Institute, Providence Cancer Institute of Oregon, Portland (R.E.S.); Mayo Clinic, Rochester, MN (A.S.M.); the Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (J.-Y.H.); Chris O'Brien Lifehouse, Camperdown, NSW, Australia (M.B.); Royal Marsden Hospital NHS Foundation Trust and the Institute of Cancer Research, London (S.P.), and Janssen Research and Development, High Wycombe (A.B.) - both in the United Kingdom; Barretos Cancer Hospital, Barretos, Brazil (J.M.D.); Istanbul Medeniyet University, Prof. Dr. Suleyman Yalcin City Hospital, Istanbul, Turkey (M.G.); Janssen Research and Development, Raritan, NJ (J.X.); Janssen Research and Development, Spring House, PA (T.A., R.E.K.); and Institut Curie, Institut du Thorax Curie-Montsouris, Paris, and Paris Saclay University, Université de Versailles Saint-Quentin-en-Yvelines, Versailles - both in France (N.G.).
N Engl J Med. 2023 Nov 30;389(22):2039-2051. doi: 10.1056/NEJMoa2306441. Epub 2023 Oct 21.
Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor () exon 20 insertions who have had disease progression during or after platinum-based chemotherapy. Phase 1 data showed the safety and antitumor activity of amivantamab plus carboplatin-pemetrexed (chemotherapy). Additional data on this combination therapy are needed.
In this phase 3, international, randomized trial, we assigned in a 1:1 ratio patients with advanced NSCLC with exon 20 insertions who had not received previous systemic therapy to receive intravenous amivantamab plus chemotherapy (amivantamab-chemotherapy) or chemotherapy alone. The primary outcome was progression-free survival according to blinded independent central review. Patients in the chemotherapy group who had disease progression were allowed to cross over to receive amivantamab monotherapy.
A total of 308 patients underwent randomization (153 to receive amivantamab-chemotherapy and 155 to receive chemotherapy alone). Progression-free survival was significantly longer in the amivantamab-chemotherapy group than in the chemotherapy group (median, 11.4 months and 6.7 months, respectively; hazard ratio for disease progression or death, 0.40; 95% confidence interval [CI], 0.30 to 0.53; P<0.001). At 18 months, progression-free survival was reported in 31% of the patients in the amivantamab-chemotherapy group and in 3% in the chemotherapy group; a complete or partial response at data cutoff was reported in 73% and 47%, respectively (rate ratio, 1.50; 95% CI, 1.32 to 1.68; P<0.001). In the interim overall survival analysis (33% maturity), the hazard ratio for death for amivantamab-chemotherapy as compared with chemotherapy was 0.67 (95% CI, 0.42 to 1.09; P = 0.11). The predominant adverse events associated with amivantamab-chemotherapy were reversible hematologic and EGFR-related toxic effects; 7% of patients discontinued amivantamab owing to adverse reactions.
The use of amivantamab-chemotherapy resulted in superior efficacy as compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC with exon 20 insertions. (Funded by Janssen Research and Development; PAPILLON ClinicalTrials.gov number, NCT04538664.).
阿维鲁单抗已被批准用于治疗在铂类化疗期间或之后疾病进展的表皮生长因子受体（EGFR）外显子 20 插入的晚期非小细胞肺癌（NSCLC）患者。1 期数据显示了阿维鲁单抗联合卡铂-培美曲塞（化疗）的安全性和抗肿瘤活性。需要更多关于这种联合治疗的数据。
在这项国际、3 期、随机试验中，我们按照 1:1 的比例将未经系统治疗的晚期 NSCLC 患者与 EGFR 外显子 20 插入患者随机分配，接受静脉注射阿维鲁单抗联合化疗（阿维鲁单抗-化疗）或单独化疗。主要终点是盲法独立中心评估的无进展生存期。化疗组中疾病进展的患者允许交叉接受阿维鲁单抗单药治疗。
共有 308 名患者接受了随机分组（153 名接受阿维鲁单抗-化疗，155 名接受单独化疗）。阿维鲁单抗-化疗组的无进展生存期明显长于化疗组（中位无进展生存期分别为 11.4 个月和 6.7 个月；疾病进展或死亡的风险比为 0.40；95%置信区间 [CI]，0.30 至 0.53；P<0.001）。在 18 个月时，阿维鲁单抗-化疗组有 31%的患者无进展生存，化疗组有 3%的患者无进展生存；数据截止时报告完全或部分缓解的分别为 73%和 47%（缓解率比为 1.50；95%CI，1.32 至 1.68；P<0.001）。在中期总体生存分析（33%成熟度）中，与化疗相比，阿维鲁单抗-化疗的死亡风险比为 0.67（95%CI，0.42 至 1.09；P=0.11）。与阿维鲁单抗-化疗相关的主要不良事件是可逆的血液学和 EGFR 相关毒性；由于不良反应，7%的患者停止使用阿维鲁单抗。
与单独化疗相比，阿维鲁单抗-化疗作为 EGFR 外显子 20 插入晚期 NSCLC 患者的一线治疗，疗效更优。（由 Janssen Research and Development 资助；PAPILLON ClinicalTrials.gov 编号，NCT04538664）。
