For a family sitting across from an oncologist after a lung cancer diagnosis, the first question is usually the plainest one: what are the options? In August 2024, the answer got a little longer for some patients.
OncoDaily dates the FDA approval to August 19, 2024. The agency cleared lazertinib, sold as Lazcluze, to be used together with amivantamab-vmjw (Rybrevant), both made by Janssen Biotech. The pair is meant as first treatment for adults whose non-small cell lung cancer is locally advanced or has spread, and whose tumors carry certain EGFR changes: exon 19 deletions or exon 21 L858R substitutions, found with an FDA-approved test. OncLive, which puts the decision on August 20, notes that patients with the L858R change often respond less well to the current third-generation drugs of this type.
What the trial showed
The approval rests on the phase 3 MARIPOSA trial, which compared the combination with osimertinib (Tagrisso), now a standard first-line pill. Each arm had 429 patients. Those on the combination went a median of 23.7 months before their disease progressed, against 16.6 months on osimertinib. Oncology Nursing News described the combination as cutting the risk of progression or death by 30%.
Survival is less settled. OncLive reported that at a median follow-up of 31.1 months, median overall survival had not yet been reached with the combination, versus 37.3 months with osimertinib. The hazard ratio was 0.77. One oncologist, Amol Akhade, was blunt on LinkedIn: this regimen is reported to be more toxic, he wrote, with no observed overall survival benefit yet. The question he posed was whether doctors would change their practice. For many, he suggested, the answer may be no, though some selected cases could be different.
Joshua Sabari of NYU Langone, speaking to OncLive, took a more hopeful view. He called it “the first therapeutic option that broadly targets EGFR mutations.” He added that upwards of 20% to 25% of people with non-small cell lung cancer have an activating EGFR mutation, so the group who might benefit is not small.
The human side of the side effects
None of this comes free. The most common reactions, seen in at least 20% of patients on the combination, were rash, nail toxicity, infusion-related reactions to amivantamab, musculoskeletal pain, swelling, mouth sores, blood clots in the veins, tingling or numbness, fatigue, diarrhea, constipation, COVID-19 infection, bleeding, dry skin, poor appetite, itching, nausea and eye problems.
That is a long list, and for families it means a real adjustment. Sabari said the infusion reactions and skin problems tied to amivantamab need better management. Ishwaria Subbiah of the Sarah Cannon Research Institute welcomed the approval and said it was time to get a supportive-care symptom plan ready for patients.
Anyone weighing this treatment should ask their oncologist how the benefits and the side effects apply to their own tumor and health.
Sources
- What oncologists say about the new approval of Lazertinib and amivantamab for advanced NSCLC – OncoDaily
- Oncology Drugs Approved by the FDA in August 2024 | Oncology Nursing News
- FDA Approval of Amivantamab Plus Lazertinib Builds Upon Success of First-Line TKIs (OncLive)
