ELCC 2025: Amivantamab Plus Lazertinib Effective in EGFR-Mutated NSCLC Versus Standard of Care

In an interview with Pharmacy Times®, Nicolas Girard, MD, professor of respiratory medicine and thoracic oncology at the Claude Bernard University in Lyon, France, and senior attending physician in the thoracic oncology service of the Hospices Civils de Lyon, explains the significance of results from the phase 3 MARIPOSA trial, which demonstrated the benefit of a amivantamab (Rybrevant; Johnson & Johnson)-lazertinib (Lazcluze; Johnson & Johnson) combination versus the historical standard of care osimertinib (Tagrisso; AstraZeneca) in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). The combination led to improvements in both progression-free survival and overall survival as a first-line treatment, according to Girard, though it was accompanied by an increased rate of dermatologic adverse events.

Girard explains how oncology treatment providers and specialty pharmacists can interpret these results and adhere to guidelines that include recommendations for amivantamab-lazertinib treatment to optimize patient care for this disease.

Pharmacy Times: Can you elaborate on the clinical significance of these findings for patients with EGFR-mutated non-small cell lung cancer (NSCLC)?

Nicolas Girard, MD: MARIPOSA demonstrates the benefit of amivantamab (Rybrevant; Johnson & Johnson)-lazertinib (Lazcluze; Johnson & Johnson) versus the historical standard of care, which is osimertinib (Tagrisso; AstraZeneca), not only in terms of progression-free survival (PFS), but also in terms of overall survival (OS). We expect more than 12 months median OS difference between osimertinib and amivantamab plus lazertinib. This is a reduction by 25% in the risk of death when using amivantamab plus lazertinib versus ssimertinib. It shows that we can improve the duration of first-line treatment. Amivantamab plus lazertinib also significantly prolongs PFS versus osimertinib to an OS benefit, so patients will live longer and disease-free thanks to this combination that is delivered in the first-line setting. We have this prolonged effect of amivantamab plus lazertinib that clearly changes the natural history of the disease.

Pharmacy Times: What specific dermatologic adverse events (AEs) are associated with this treatment, and how does the preventative regimen mitigate these effects?

Nicolas Girard, MD: With amivantamab plus lazertinib, we have a higher rate of dermatologic AEs that include rash, paronychia, pruritus on the scalp, and erythema. These AEs are known to be associated with epidermal growth factor receptor (EGFR)-signaling pathway inhibition. The COCOON trial aimed to assess whether a prophylactic dermatologic regimen could reduce the incidence of those dermatological adverse events. In COCOON, we have this prophylactic regimen with doxycycline and a ceramides-based moisturizer on the body and face. We also had clindamycin lotion on the scalp and chlorhexidine for the nails. It was compared to the standard of care, which is often restricted to reactive treatment with steroids or antibiotics. COCOON showed that with prophylaxis, we can reduce by 50% the incidence of those grade 2 or higher AEs, from 77% of the patients with a standard management to 39% of the patients with the COCOON prophylaxis. It clearly changes the way the patients are experiencing the treatment and increases the quality of life of patients. We also have a reduction in the risk of dose modification or discontinuation of amivantamab plus lazertinib with the COCOON regimen.

Pharmacy Times: Given the superior overall survival results versus osimertinib, how might this combination therapy influence current first-line treatment guidelines for EGFR-mutated NSCLC?​

Nicolas Girard, MD: It's changing the game. It's clearly a new standard of care. It is the only treatment that is increasing OS versus osimertinib, so obviously, we expect a majority of patients to receive amivantamab plus lazertinib in the first-line setting. It is part of the guidelines; the European Society for Medical Oncology clinical practice guidelines and National Comprehensive Cancer Network guidelines have included the MARIPOSA regimen based on the PFS data. Now that we have the OS data, it's obviously increasing the magnitude of benefit.

Pharmacy Times: Could you discuss the potential mechanisms by which amivantamab and lazertinib work synergistically to achieve improved outcomes compared with the standard of care?

Nicolas Girard, MD: Through the dual targeting of the EGFR protein, with amivantamab targeting the extracellular part and lazertinib inhibiting the kinase inhibitor inside the cytoplasm. We have a deep inhibition of the EGFR-signaling pathway, deeper than what we have with tyrosine kinase inhibitors alone. We also have some immune-mediated effects with antibody-dependent cellular toxicity (ADCC) and trogocytosis, probably increasing the inhibition of the EGFR signaling pathway in those patients. What we saw from the resistance mechanisms after MARIPOSA is that we are clearly changing the biology and the biological history of the disease with the combination versus osimertinib.

Pharmacy Times: Considering the evolving landscape of targeted therapies in oncology, what role do you foresee for pharmacists in managing and counseling patients undergoing treatment with the amivantamab and lazertinib combination?

Nicolas Girard, MD: Obviously, it's a new combination. It's the first time, to my knowledge, in toxic oncology, a combination of an intravenous drug plus an oral drug. It is a very new setting for the management of those patients, including the delivery of amivantamab at the hospital and at the day hospital, and also delivering lazertinib, which is part of the combination that the patient will have to take orally every day. It's also very important to manage the observance of the oral drug, making sure that you have an early identification of the AEs as well. It is quite a new setting for the delivery of those drugs. What we also expect, and it was approved in Europe, is that amivantamab will soon become available as a subcutaneous formulation, which will also facilitate the administration. It could be a way to an at-home administration method, which would lead the MARIPOSA regimen to be feasible outside the hospital, which is obviously something that will even more improve the quality of life of patients.