FDA Approval Marks Amivantamab's Milestone in EGFR+ NSCLC


In this episode, Joshua K. Sabari, MD, discusses the FDA approval of amivantamab plus chemotherapy as a first-line treatment for patients with EGFR exon 20 insertion mutation-positive non-small cell lung cancer.

In the recent episode of Targeted Talks, Joshua K. Sabari, MD, assistant professor of medicine, thoracic medical oncology, Perlmutter Cancer Center NYU Langone Health, and director of High Reliability Organization Initiatives at the Perlmutter Cancer Center, discusses the significant FDA approval of amivantamab-vmjw (Rybrevant) in combination with carboplatin and pemetrexed as a first-line treatment for patients diagnosed with EGFR exon 20 insertion mutation-positive non-small cell lung cancer (NSCLC).

This approval stems from the results of the phase 3 PAPILLON study (NCT04538664), which demonstrated substantial improvements in progression-free survival (PFS).1 Patients receiving the combination therapy experienced a PFS of 11.4 months (95% CI, 9.8-13.7) compared with 6.7 months (95% CI, 5.6-7.3) for those treated solely with carboplatin and pemetrexed. The hazard ratio for PFS was 0.40, indicating a significant reduction in disease progression risk (P <.0001).

“As of now, amivantamab is the only therapy that has shown an improvement in progression-free survival, the only therapy that has shown an improvement in response rate in the frontline setting in a randomized trial, and it is the only FDA-approved…targeted therapy in the frontline setting,” Sabari explains.

The PAPILLON trial, which enrolled 308 patients with EGFR exon 20 insertion mutations, evaluated the efficacy of amivantamab with or without carboplatin and pemetrexed. The trial's primary end point was PFS, with overall survival (OS) as the key secondary endpoint. Other secondary endpoints included objective response rate, duration of response, PFS after first subsequent therapy, time to symptomatic progression, intracranial PFS, and incidence and severity of adverse events (AEs).

Eligible patients had locally advanced or metastatic NSCLC with primary EGFR exon 20 insertion activating mutation, an ECOG performance status of 0 or 1, and agreed to genetic characterization of tumor status. They were ineligible if they had untreated brain metastases, contraindications to carboplatin or pemetrexed, or a hypersensitivity to vitamin B12 or folic acid.

Further efficacy findings also showed OS data to be immature at the time of analysis, with 44% of prespecified deaths for the final analysis, showing no trend towards detriment.

Regarding safety, common AEs observed with the combination therapy included rash, nail toxicity, stomatitis, infusion-related reactions, fatigue, edema, constipation, decreased appetite, nausea, COVID-19, diarrhea, and vomiting.

Furthermore, the FDA granted traditional approval to amivantamab for the treatment of adult patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy.

This approval marks a significant advancement in the treatment landscape for EGFR exon 20 insertion mutation-positive NSCLC, providing new hope for patients facing this challenging disease.

“I think if you meet a patient with an EGFR exon 20 insertion mutation in 2024, the PAPILLON regimen of amivantamab plus chemotherapy is the standard of care option. Clearly, there are clinical trials looking to improve upon that for our patients,” Sabari says.

  1. FDA approvesamivantamab-vmjw for EGFR exon 20 insertion-mutated non-small cell lung cancer indications. News release. FDA. March 1, 2024. Accessed March 14, 2024. https://tinyurl.com/2p9v9632
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