2378 - Evaluating Outcomes in NSCLC Patients Receiving Amivantamab and Intracranial Radiation
Presenter(s)
N. Howard1, A. L. Schwer2, S. Szeja3, Y. Liu4, P. Lee2, T. M. Williams5, D. Nguyen6, J. Malhotra7, A. Rock4, R. Muddasani4, M. Lee4, L. Antrim4, R. Salgia4, C. J. Ladbury5, and A. Amini5; 1Western University of Health Sciences, College of Osteopathic Medicine of the Pacific, Pomona, CA, United States, 2Department of Radiation Oncology, Orange County Lennar Foundation Cancer Hospital, Irvine, CA, 3Department of Radiation Oncology, City of Hope National Medical Center, Upland, CA, 4City of Hope, Duarte, CA, 5Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, 6Department of Medical Oncology & Therapeutics Research, Orange County Lennar Foundation Cancer Hospital, Irvine, CA, 7City of Hope, Irvine, CA
Purpose/Objective(s): Amivantamab is an approved epidermal growth factor (EGFR) MET bispecific antibody for non-small cell lung (NSCLC) patients with certain EGFR mutations. There is currently limited data evaluating the safety, efficacy, and durability of combining amivantamab with radiation. Here we report a series of patients who received both radiation and amivantamab, evaluating toxicities and outcomes while on therapy.
Materials/Methods: Consecutive patients treated with amivantamab and radiation (within 6 months of an amivantamab infusion) at a single institution from 2022 through 2024 were included. Toxicity was reported based on the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Overall survival was examined using the Kaplan-Meier method. Univariate survival analysis was performed with the log-rank test with Cox proportional hazards regression used to estimate hazard ratios (HR).
Results: A total of 17 patients received either intracranial or extracranial radiation while on their bispecific. Six patients received amivantamab concurrent with radiation while 6 and 5 patients received radiation prior to or after their course of amivantamab, respectively. Nine patients received intracranial radiation (6: stereotactic radiosurgery; 3 whole brain/craniospinal radiation). Extracranial sites included bone (n=6), lung (n=1), and lymph nodes (n=1). Median age was 66 yrs (27-83 yrs). Median follow up was 9 months (range, 1-21 months). A slight majority were female (53%), of Asian descent (59%), and with EGFR exon 20 insertion mutation (53%). Median duration of amivantamab was 9 months (1-21 months). Median survival from the start of amivantamab was 10 months (95% CI 7.6-12.6) with Asian race being most significantly associated with survival (HR 0.495; p=0.019). Five patients (29%) progressed intracranially; 10 patients (59%) progressed extracranially. The most common site of radiation while on amivantamab was the brain (53%), followed by bone (35%). Median time to intracranial and extracranial progression was 7.1 (3-33 months) and 7.6 months (1-24 months) respectively. Three patients experienced grade 3 drug-related pneumonitis; 2 of these patients were on prior therapy and none had prior thoracic radiation. No additional grade = 3 toxicities were reported including radiation brain necrosis.
Conclusion: Combination amivantamab and radiation appeared safe both intracranially and extracranially with no reports of intracranial radiation necrosis. Further large-scale studies are warranted to assess the safety and efficacy of combining novel bispecific antibodies with radiation, particularly in the oligometastatic and oligoprogressive settings, to improve progression-free survival and overall survival.