Subcutaneous regimen did not produce any new safety signals.
Subcutaneous amivantamab-vmjw administered once every 4 weeks plus daily lazertinib could be an equally effective and more convenient treatment for EGFR-mutant non-small cell lung cancer as the FDA-approved IV regimen.
Data from the PALOMA-2 trial -- presented at International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer -- showed patients who received the subcutaneous therapy had similar outcomes as those who were treated with IV amivantamab-vmjw (Rybrevant, Janssen) every 2 weeks plus lazertinib (Lazcluze, Janssen) in the phase 3 MARIPOSA trial.
"For a first-line treatment where we hope patients are on targeted therapy for months or years, the 50% reduction in visits to the infusion center makes a big difference," Susan C. Scott, MD, assistant professor of oncology at Johns Hopkins University School of Medicine and thoracic medical oncologist at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center at Sibley Memorial Hospital, told Healio.
Healio previously reported on the MARIPOSA trial, which showed patients with EGFR-mutated advanced NSCLC derived a 25% OS benefit from first-line IV amivantamab-vmjw every 2 weeks plus lazertinib compared with osimertinib (Tagrisso, AstraZeneca).
Patients who received amivantamab-vmjw plus lazertinib had an objective response rate of 86%, according to study background.
The FDA approved the regimen in August 2024.
Scott and colleagues evaluated subcutaneous amivantamab-vmjw plus lazertinib in the PALOMA-2 trial.
They previously reported on two other cohorts that received first-line subcutaneous amivantamab-vmjw every 2 weeks plus lazertinib and had a similar response rate to those who received the IV regimen.
A separate cohort of 77 patients (median age, 63 years; range, 31-80; 68% women; 62% Asian) with treatment-naive locally advanced or metastatic EGFR-mutated NSCLC received subcutaneous amivantamab-vmjw every 4 weeks plus lazertinib.
The regimen included 1,600 mg amivantamab-vmjw in the first 4 weeks and 3,520 mg in subsequent 28-day cycles, as well as 240 mg lazertinib daily.
Investigator-assessed ORR served as the primary endpoint. Independent central review (ICR)-assessed ORR, duration of response, time to response, clinical benefit rate, PFS, OS, safety and pharmacokinetics served as secondary endpoints.
Participants had an investigator-assessed ORR of 82% (95% CI, 71%-90%) and ICR-assessed ORR of 87% (95% CI, 77%-94%).
They had a confirmed investigator-assessed ORR of 79% (95% CI, 69%-88%) and ICR-assessed ORR of 83% (95% CI, 73%-91%).Patients had a median time to response of 8.1 weeks (7-16.5). The median duration of response could not be estimated.
Median PFS and OS could not be estimated, either.
"The subcutaneous amivantamab formulation every 4 weeks yields similar results to the
intravenous formulation every 2 weeks and the subcutaneous formulation every 2 weeks, which is what we expected," Scott told Healio.
The most common treatment-related adverse events included paronychia (73%), hypoalbuminemia (64%), rash (58%), dermatitis acneiform (40%) and stomatitis (38%).
The most common grade 3 or worse treatment-related adverse events included rash (12%), dermatitis acneiform (8%), hypoalbuminemia (5%) and paronychia (5%).
In all, 8% of participants discontinued treatment due to adverse events.
Most patients (87%) received prophylactic anticoagulation.
Venous thromboembolism (VTE) occurred in 13% of participants. However, researchers did not observe any grade 3 or worse VTE events, and no one stopped treatment, reduced dose or died from VTE.
"No new safety signals were identified," Scott said during her presentation.
"There are now three approved options for first-line treatment of EGFR-mutant lung cancer, and further studies are needed to help providers and patients choose the best regimen for each patient," she told Healio. "The approaches are quite different, and it's not likely to be a one-size-fits-all solution.
"The PALOMA-3 study demonstrated improved survival and decreased VTE risk with subcutaneous amivantamab compared to intravenous amivantamab in later lines of treatment," Scott added. "Better defining long-term outcomes for subcutaneous amivantamab with lazertinib in the frontline will be important as we consider different options with our patients."