Dexamethasone Prophylaxis Reduces IRRs in Amivantamab Treatment
Pretreatment with dexamethasone significantly reduced infusion-related reactions in patients receiving amivantamab for advanced lung cancer, according to findings from the SKIPPirr study.
Lung with cancer cells: © catalin - stock.adobe.com
The phase 2 SKIPPirr study (NCT05663866) has shown that pretreatment with dexamethasone significantly reduces infusion-related reactions (IRRs) in patients receiving intravenous (IV) amivantamab-vmjw (Rybrevant) for the treatment of advanced non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or L858R substitution mutations.1
These findings were presented at the 2024 World Conference on Lung Cancer.
A total of 40 patients were included in the study, and the primary end point of incidence of infusion-related reactions (IRRs) at day 1 of cycle 1 was met, with prophylaxis with dexamethasone at a dose of 8 mg taken for 2 days prior to the first infusion. The all-grade IRR rate for IV amivantamab was 22.5%, demonstrating a 3-fold reduction in the incidence of IRRs vs standard management of IRRs with IV amivantamab, which had an all-grade IRR rate of 67.4%.
For safety, all IRRs were grade 1 or 2. No patients needed to be hospitalized due to IRRs, and no grade 3 or higher IRR events were reported. Further, the safety profile ofamivantamab and lazertinib (Lazcluze) with prophylactic dexamethasone at the start of treatment was consistent with previous studies, and the most frequently seen IRR-related symptoms observed in the study included nausea (8%), dyspnea (5%), and hypotension (5%).
“Steroids at an 8 mg dosing decreased the incidence of infusion-related reactions,” said Alex Spira, MD, PhD, FACP, medical oncologist at Virginia Cancer Specialists and US Oncology, in an interview with Targeted OncologyTM. “I think everybody who is getting amivantamab should get it pretreatment, as long as they are getting the IV version. Once the subcutaneous version comes about, it will be clearly relevant.”
Alex Spira, MD, PhD, FACP
"These data offer important insights that may help improve the patient experience with intravenous amivantamab treatment," Gilberto Lopes, MD, associate director of global oncology at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, and presenting author, said in a press release. "This study shows us that an easily accessible approach of an increased dose regimen of dexamethasone as a pretreatment prophylaxis can potentially help lower IRRs. It is encouraging to see a 3-fold decrease in IRRs, when comparing the rates in SKIPPirr to historical data."
About the SKIPPirr Study
The phase 2, open-label SKIPPirr study is assessing the combination of amivantamab with lazertinib in patients with EGFR-mutated advanced NSCLC. These patients must have disease progression on osimertinib (Tagrisso) and platinum-based chemotherapy.2
A Simon's 2-stage design was utilized in the study to examine various preventive treatments across 4 groups:
- Group 1 received oral dexamethasone 4 mg taken twice daily on the day before treatment for a total of 2 doses.
- Group 2 was given dexamethasone 8 mg taken orally twice daily on the 2 days leading up to treatment and the morning of infusion for a total of 5 doses.
- Group 3 was given oral montelukast (Singulair) 10 mg, which began 4 days before treatment and continued through the day of treatment for a total of 5 doses.
- Group 4 was given a single dose of methotrexate 25 mg, which was administered as a subcutaneous injection between days –7 and –3 before the treatment.
Enrollment was open to patients with advanced or metastatic NSCLC who had an ECOG performance status of 0 or 1, progressed on or after prior treatment with osimertinib and platinum-based chemotherapy, and had an EGFR mutation. Prior use of first- or second- generation EGFR tyrosine kinase inhibitors was allowed if it was given before treatment with osimertinib.
Secondary end points of the study include incidence of adverse effects of IRRs, percentage of patients with IRRs, duration of infusion time, overall response rate, and duration of response.
REFERENCES:
Dexamethasone reduces infusion-related reactions in patients with EGFR-mutated non-small cell lung cancer treated with intravenous RYBREVANT® (amivantamab-vmjw). News release. Johnson & Johnson. September 10, 2024. Accessed September 11, 2024. https://tinyurl.com/bdh9w2kj
Premedication to reduce amivantamab associated infusion related reactions. ClinicalTrials.gov. Updated August 14, 2024. Accessed September 11, 2024. https://clinicaltrials.gov/study/NCT05663866
