The Butterfly Flies - Practice Changing Results of PAPILLON, First Line Chemotherapy and Amivantamab for the Treatment of NSCLC Patients with EGFR Exon 20 Insertions

Abstract

Epidermal growth factor receptor (EGFR) exon 20 insertions are a rare subtype of EGFR mutations that do not respond to EGFR tyrosine kinase inhibitors developed for sensitizing mutations. In 2021, two drugs, amivantamab and mobocertinib each received FDA accelerated approval for second line use after platinum based therapy. These drugs were then brought to first line setting clinical trials; PAPILLON and EXCLAIM2. PAPILLON, which compared amivantamab plus chemotherapy to chemotherapy was positive, whereas EXCLAIM2, which compared mobocertinib to chemotherapy was negative. The PAPILLON regimen received subsequent FDA approval. In this commentary, we review the details of PAPILLON and also discuss why the rival trial, EXCLAIM2, may have failed.

Keywords:

• epidermal growth factor receptor
• EGFR
• first line therapy
• targeted therapy
• bispecific antibody
• mobocertinib

Disclosure

Dr Misako Nagasaka reports personal fees from AstraZeneca, Daiichi Sankyo, Novartis, EMD Serono, Pfizer, Lilly, Genentech, Regeneron, BMS, Caris Life Sciences, Takeda, Janssen, Blueprint Medicine, Mirati; non-financial support from AnHeart Therapeutics, outside the submitted work. The authors report no other conflicts of interest in this work.