Based on results from the phase II SKIPPirr trial, the addition of 8 mg of dexamethasone to standard infusion-related reaction prophylaxis appeared to reduce the incidence of such events by approximately threefold in patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC) who were intravenously treated with the bispecific anti–EGFR-MET antibody amivantamab-vmjw. In the Journal of Thoracic Oncology, Spira et al stated that this technique may be readily implemented in clinical practice.
“Intravenous amivantamab has received regulatory approvals around the world in multiple indications for EGFR-mutated advanced NSCLC as monotherapy or in combination with chemotherapy or [the third-generation tyrosine kinase inhibitor] lazertinib,” the investigators commented. “[However], intravenous amivantamab is associated with a 67% infusion-related reaction rate.”
Study Details
Patients with EGFR-mutated (exon 19 deletion or exon 21 L858R) advanced NSCLC who experienced disease progression after treatment with osimertinib and platinum-based chemotherapy were eligible for enrollment. The entire study population received standard premedication with antihistamines, antipyretics, and 10 mg of intravenous dexamethasone, followed by 1,050 mg (1,400 mg if ≥ 80 kg) of intravenous amivantamab once weekly for 4 weeks and then every 2 weeks thereafter, in combination with 240 mg of oral lazertinib daily.
Four independent prophylactic approaches were evaluated using Simon’s two-stage design, with an expansion stage if a cohort passed both stages: 4 mg of oral dexamethasone twice daily on the day before the first day of the first cycle of treatment with amivantamab plus lazertinib (n = 6); 8 mg of oral dexamethasone twice daily for the 2 days before and on the morning of the first day of the first cycle (n = 41); 10 mg of oral montelukast once daily for the 4 days before and on the first day of the first cycle (n = 15); and a single dose of 25 mg of subcutaneous methotrexate any time between 7 and 3 days before the first day of the first cycle (n = 6).
The incidence of infusion-related reactions on the first day of the first cycle of treatment was evaluated as the primary endpoint.
Key Findings
The cohort that received 8 mg of dexamethasone was found to have passed the first two stages and thus proceeded to the expansion stage, during which 24 additional patients were treated. A total of 22.5% (n = 9 of 40) of patients experienced an infusion-related reaction on the first day of the first cycle of treatment; this represents an approximate threefold decrease vs historical data (67.4%). By the end of the third cycle, 24.4% (n = 10 of 41) of those who were treated with 8 mg of dexamethasone experienced an immune-related reaction; all infusion-related reactions were grade 1 or 2, except for one grade 3 toxicity reported on the first day of the second cycle. The safety and efficacy profiles of amivantamab plus lazertinib appeared to be consistent with those observed in previous reports.
The investigators concluded: “Timely adoption of the convenient dexamethasone 8 mg twice daily regimen to reduce infusion-related reactions and the prophylactic dermatologic adverse event management under evaluation in the COCOON study (ClinicalTrials.gov identifier NCT06120140) could have an immediate clinical impact by enhancing safety and tolerability of intravenous amivantamab while allowing patients to initiate and remain on therapy.”
Alexander I. Spira, MD, PhD, FACP, of Virginia Cancer Specialists, Fairfax, is the corresponding author of the Journal of Thoracic Oncology article.
Disclosure: The study was funded by Janssen Research & Development, LLC, a Johnson & Johnson company. For full disclosures of the study authors, visit jto.org.
