JL1031E: Risk and Management of Intracranial Progression on Amivantamab in Epidermal Growth Factor Receptor (EGFR) Exon 20 insertion (ex20ins)-mutated Non-small Cell Lung Cancer (NSCLC)

Background:
Amivantamab, an EGFR-MET bispecific antibody, is approved for the treatment of advanced EGFR ex20ins NSCLC patients (pts) that have progressed on platinum-based chemotherapy. In this exploratory analysis, we investigated the patterns of progression on amivantamab therapy among pts in this population.

Methods:
The CHRYSALIS study (NCT02609776) enrolled pts with advanced NSCLC and allowed the inclusion of pts with treated brain metastases. Baseline brain MRI was required at screening in the dose expansion phase; however, postbaseline surveillance MRIs were performed according to local practice and not required per protocol. Sites of target, non-target, and new lesion progression were reported. This analysis includes 114 post-platinum pts with EGFR ex20ins NSCLC who received amivantamab on or before Jun 4, 2020 (110 from dose expansion).

Results:
At the Mar 30, 2021 data cutoff (median follow-up of 12.5 months [range, 0.2–30.5]), RECIST-defined PD was described in 72 of 114 pts (63%), 25 of whom continued amivantamab post progression for a median of 4.2 additional months (range, 1.0–12.5). Baseline brain metastases were reported in 38 of 114 pts. 13 pts (11.4%) had intracranial disease as sole site of progression, 4 had intra- and extracranial progression, and 55 had extracranial progression (most common in lung, bone, lymph node, and liver). 8 of 13 pts with intracranial-only progression had a history of brain metastases at baseline. The median time to progression for pts with intracranial-only progression was 4.5 months (range, 1.4–16.6), as compared with 5.5 months (range, 0.6–24.1) for those pts with systemic progression.

6 of 13 pts with intracranial-only progression underwent stereotactic radiosurgery (SRS) while continuing amivantamab. Adverse events temporally associated with SRS were nausea (10 days after SRS) and fatigue, reported in 1 pt each. For these 6 pts, the median duration of amivantamab treatment after progression was 4.0 months (range, 2.3–6.0).

Conclusions:
Intracranial-only progression on amivantamab therapy occurred in 11.4% of pts. Treatment of brain progression with SRS while continuing amivantamab appears feasible and tolerable.