APPs provide an in-depth look at amivantamab plus lazertinib for the treatment of patients with locally advanced or metastatic non–small cell lung cancer.
This drug combination has a wide range of toxicities requiring careful monitoring. Proactive skin care and minimizing exposure to sun should be emphasized. Providers should pay particular attention to the psychological effects of skin toxicity and provide resources and reassurance as needed.
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WHO IS THIS DRUG APPROVED FOR?
On August 20, 2024, the FDA approved amivantamab plus lazertinib as a first-line chemotherapy-free treatment of locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R substitution mutations.1 This is a category 1 recommendation for this indication in the National Comprehensive Cancer Network guidelines.2
WHAT EFFICACY DATA BACK IT UP?
This approval was based on the results of the phase 3 MARIPOSA trial (NCT04487080), which showed amivantamab and lazertinib, when compared with osimertinib for first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, reduced the risk of disease progression by 30% (23.7 months vs 16.6 months; HR 0.70; 95% CI, 0.58-0.85). Data showed a median duration of response that was 9 months longer than that with osimertinib (25.8 months vs 16.7 months).3
HOW IT WORKS
Amivantamab is a bispecific antibody that blocks EGFR and MET activity, degrades EGFR and MET, and activates immune cell responses.4
Lazertinib is a highly selective, brain-penetrating third-generation tyrosine kinase inhibitor that specifically targets EGFR.5
HOW IT’S ADMINISTERED
Amivantamab is administered intravenously. Careful attention must be paid to the rate of infusion, which is gradually increased over the first 4 weeks of treatment and
varies based on the dose.6
Amivantamab has a high incidence of infusion-related reaction (IRR) during the first infusion and therefore should be given via peripheral line on week 1 and week 2. Central line may be used for administration of all subsequent doses.6 We recommend patients be seated near the nurses’ station during week 1 and that the treating nurse be aware of the high likelihood of IRR. In addition, the nurse should have emergency medications ready and have access to the patient’s provider in case of reaction.
Premedication with antihistamines and antipyretics is required for all doses. Administer additional premedication with glucocorticoid on day 1 and 2 of week 1. Subsequent premedication with glucocorticoid is optional if there was no IRR during the prior administration.6
After prolonged dose interruption, include glucocorticoid premedication upon reinitiation.6
Lazertinib is an oral tablet and should not be crushed, split, or chewed. Strong and moderate CYP3A4 inducers should be avoided with this drug.6
THE RECOMMENDED DOSE
The dose of amivantamab is based on patient weight:
Less than 80 kg: 1050 mg
More than 80 kg: 1400 mg
The recommended dosage of lazertinib is 240 mg by mouth once daily with or without food. It should be administered in combination with amivantamab. Lazertinib should be taken prior to amivantamab when given on the same day.2
HOW TO MANAGE ASSOCIATED ADVERSE EVENTS (AES)
Serious AEs were reported in 49% of patients in the MARIPOSA trial. Proactive supportive care is critical to reduce the risk and severity of some AEs. Close monitoring and accurate Common Terminology Criteria for Adverse Events (CTCAE) grading of symptoms is essential to properly manage AEs. Refer to the package insert for detailed management guidelines.
WHAT TO INFORM PATIENTS ABOUT TO START TREATMENT
Prophylactic measures are critical to mitigate the incidence and severity of AEs.
It is important that patients understand the symptoms of IRR prior to starting therapy and when to report symptoms to their infusion therapy nurse.
Patients should avoid sun exposure and use sunscreen during treatment and for 2 months after discontinuation.
Patients should also be informed about the symptoms of VTE and ILD and be encouraged to promptly report any concerning signs.
Amivantamab and lazertinib can cause fetal harm. Both male and female patients of childbearing age should use effective contraception while receiving treatment and for 3 months after stopping amivantamab, as well as for 3 weeks after the last dose of lazertinib.5
REFERENCES
