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Intracranial and systemic progression on amivantamab in platinum-treated epidermal growth factor receptor exon 20
Natasha B Leighl1, Jose Trigo2, Keunchil Park3
1Princess Margaret Cancer Centre, Toronto, Canada.
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.
Insights
Amivantamab shows antitumor activity in advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertions. Intracranial progression was uncommon, and combining amivantamab with stereotactic radiosurgery (SRS) for brain metastases was feasible.
Area of Science:
- Oncology
- Medical Science
Background:
- Amivantamab is an EGFR-MET bispecific antibody approved for advanced non-small cell lung cancer (NSCLC) with various EGFR mutations.
- Understanding disease progression sites with amivantamab is crucial for treatment management.
Purpose of the Study:
- To analyze sites of disease progression in patients with EGFR exon 20 insertion (Ex20ins) NSCLC treated with amivantamab monotherapy.
- To evaluate the feasibility and tolerability of continuing amivantamab with stereotactic radiosurgery (SRS) for intracranial progression.
Main Methods:
- Analysis of 114 participants with Ex20ins NSCLC from the CHRYSALIS trial who received amivantamab monotherapy after platinum-based chemotherapy.
- Assessment of objective response rate, duration of response, progression-free survival, and sites of progression.
- Evaluation of treatment continuation with amivantamab and SRS for participants with intracranial progression.
Main Results:
- Amivantamab monotherapy demonstrated a 43% objective response rate and a 6.7-month median progression-free survival.
- The most common sites of first progression were lungs/pleura (29%), bone (21%), and brain (15%).
- Intracranial-only progression occurred in 11% of participants; 6 participants continued amivantamab with SRS, reporting good tolerability.
Conclusions:
- Amivantamab monotherapy exhibits significant antitumor activity in post-platinum Ex20ins NSCLC.
- Intracranial progression is infrequent, and concurrent treatment with amivantamab and SRS is a feasible and tolerable option for managing brain metastases.
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