Leighl Natasha B, Trigo Jose, Park Keunchil, Lee Se-Hoon, Girard Nicolas, Viteri Santiago, Garrido Pilar, Krebs Matthew G, Thayu Meena, Knoblauch Roland E, Xie John, Bauml Joshua M, Schnepp Robert W, Londhe Anil, Xia Yichuan, Mahadevia Parthiv J, Cho Byoung Chul
Princess Margaret Cancer Centre, Toronto, Canada.
Hospital Universitario Virgen de la Victoria y Regional, IBIMA, Málaga, Spain.
Lung Cancer. 2025 Jul;205:108579. doi: 10.1016/j.lungcan.2025.108579. Epub 2025 May 10.
Amivantamab, an epidermal growth factor receptor (EGFR)-MET bispecific antibody, is approved as monotherapy and as combination therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring various EGFR mutations in first-line and refractory settings. Sites of progressive disease on amivantamab monotherapy are not well understood and could be instructive for treatment management.
CHRYSALIS (NCT02609776) enrolled participants with NSCLC, including those with treated brain metastases. Brain magnetic resonance imaging was required at screening but performed per local practice after enrollment (conducted postbaseline every 6 [±1] weeks after Cycle 1 Day 1). Sites of target, non-target, and new lesion progression were reported. This analysis includes 114 participants with EGFR exon 20 insertion (Ex20ins) NSCLC after disease progression on platinum-based chemotherapy who received amivantamab monotherapy on or before June 4, 2020.
As of March 30, 2021, the median follow-up was 12.5 months (range, 0.2-30.5). Among 114 participants, the objective response rate by blinded independent central review was 43 %; median duration of response was 10.8 months, and median progression-free survival was 6.7 months. RECIST-defined progressive disease occurred in 72/114 participants (63 %); 25/72 (35 %) continued amivantamab after progression (4.2 median additional months; range, 1.0-12.5). The most common first sites of progression were the lungs/pleura (29 %), followed by bone (21 %), brain (15 %), and lymph node (12 %). Thirteen participants (11 %) had intracranial-only first progression. Six of these 13 participants underwent stereotactic radiosurgery (SRS) while continuing amivantamab. The median duration of amivantamab treatment post-progression in these 6 participants was 4.0 months (range, 2.3-6.0). SRS was well tolerated, with 2 adverse events reported (nausea and fatigue, n = 1 each).
Amivantamab monotherapy in post-platinum Ex20ins NSCLC demonstrated meaningful antitumor activity in participants, and intracranial-only progression was infrequent. Treatment of brain progression with SRS while continuing amivantamab appears feasible and tolerable.
阿米万他单抗是一种表皮生长因子受体（EGFR）-间质上皮转化因子（MET）双特异性抗体，被批准作为单药疗法以及联合疗法，用于一线治疗和难治性情况下患有各种EGFR突变的晚期非小细胞肺癌（NSCLC）患者。阿米万他单抗单药治疗时疾病进展的部位尚未完全明确，可能对治疗管理具有指导意义。
CHRYSALIS（NCT02609776）研究纳入了NSCLC患者，包括那些已接受治疗的脑转移患者。筛查时需要进行脑磁共振成像，但入组后根据当地实际情况进行（在第1周期第1天之后每6[±1]周进行一次基线后检查）。报告了靶病灶、非靶病灶和新病灶进展的部位。该分析纳入了114例在铂类化疗后疾病进展的EGFR外显子20插入（Ex20ins）NSCLC患者，这些患者在2020年6月4日或之前接受了阿米万他单抗单药治疗。
截至2021年3月30日，中位随访时间为12.5个月（范围0.2 - 30.5个月）。在114例患者中，经盲法独立中央审查的客观缓解率为43%；中位缓解持续时间为10.8个月，中位无进展生存期为6.7个月。根据实体瘤疗效评价标准（RECIST）定义的疾病进展发生在72/114例患者中（63%）；25/72例（35%）患者在疾病进展后继续使用阿米万他单抗（中位额外使用4.2个月；范围1.0 - 12.5个月）。最常见的首个进展部位是肺/胸膜（29%），其次是骨（21%）、脑（15%）和淋巴结（12%）。13例患者（11%）首次进展仅发生在颅内。这13例患者中有6例在继续使用阿米万他单抗的同时接受了立体定向放射外科治疗（SRS）。这6例患者进展后使用阿米万他单抗的中位治疗持续时间为4.0个月（范围2.3 - 6.0个月）。SRS耐受性良好，报告了2例不良事件（恶心和疲劳，各1例）。
铂类治疗后Ex20ins NSCLC患者接受阿米万他单抗单药治疗显示出有意义的抗肿瘤活性，且仅颅内进展不常见。在继续使用阿米万他单抗的同时用SRS治疗脑转移似乎可行且耐受性良好。
