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Intracranial and systemic progression on amivantamab in platinum-treated epidermal growth factor receptor exon 20 insertion-mutated advanced non-small cell lung cancer
Leighl, N. B. Trigo, J. Park, K. Lee, S. H. Girard, N. Viteri, S. Garrido, P. Krebs, M. G. Thayu, M. Knoblauch, R. E.
Leighl, N. B.
Trigo, J.
Park, K.
Lee, S. H.
Girard, N.
Viteri, S.
Garrido, P.
Krebs, M. G.
Thayu, M.
Knoblauch, R. E.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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Date
2025
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Citation
Leighl NB, Trigo J, Park K, Lee SH, Girard N, Viteri S, et al. Intracranial and systemic progression on amivantamab in platinum-treated epidermal growth factor receptor exon 20 insertion-mutated advanced non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands). 2025 Jul;205:108579. PubMed PMID: 40446773. Epub 2025/05/31. eng.