Invited discussant Jarushka Naidoo, MBBCh, MHS, Professor of Medical Oncology and Consultant Medical Oncologist, Beaumont RCSI Cancer Centre, in Dublin, called the results of amivantamab-vmjw therapy in patients with EGFR exon 20 insertion–positive advanced non–small cell lung cancer (NSCLC) “promising and potentially practice-changing.” She said the CHRYSALIS study provides “valuable insights into potential therapeutic vulnerabilities and offers hope for improved patient outcomes.” She also noted the study is significant as the only investigation of a bispecific antibody in this population with advanced NSCLC.

Jarushka Naidoo, MBBCh, MHS

“The study demonstrates a durable benefit for nearly half of the patients, with manageable toxicities mainly driven by EGFR and MET inhibition,” said Dr. Naidoo. She also pointed out the potential therapeutic vulnerabilities in patients with co-occurring RAS/RAF/MEK alterations.

“These data demonstrate the first glimpses of biologic subsets of this type of lung cancer with specific potential therapeutic vulnerabilities that we will need to interrogate,” she continued. “Those patients who have co-occurring RAS/RAF/MEK alterations appear to have poor outcomes, which raises the question of whether combination therapies might be more effective in this specific population.”

Regarding the potential of targeted therapies for EGFR exon 20 insertions moving to the front line, Dr. Naidoo mentioned the upcoming late-phase studies that will address this question. “It will be interesting to see whether these targeted therapies, alone or in combination, can improve outcomes for patients with EGFR exon 20 insertion–positive NSCLC when used as first-line treatment.”

Finally, Dr. Naidoo emphasized the need for continued research to better understand the biology of these tumors, optimize treatment strategies, and uncover mechanisms of acquired resistance. 

DISCLOSURE: Dr. Naidoo reported financial relationships with Merck, AstraZeneca, Roche/Genentech, Pfizer, Takeda, Bayer, Daiichi Sankyo, Kaleido Biosciences, NGM Pharmaceuticals, Amgen, Regeneron, Elevation Oncology, AbbVie, Arcus Biosciences, Mirati, Bristol Myers Squibb, Medscape, OncLive, Research to Practice, and Touch Oncology.