“In patients with exon 20–mutated non–small cell lung cancer, PAPILLON established a new standard of care with amivantamab-vmjw and chemotherapy,” according to study discussant, Benjamin Besse, MD, PhD, Professor of Medical Oncology at Paris-Saclay University, Orsay, and Head of Clinical Research at Gustave Roussy Cancer Campus, Villejuif. Overall, the additive benefit of amivantamab to chemotherapy was clear, with a trend toward improvement in overall survival despite a high rate of crossover for the control arm.
![Benjamin Besse, MD, PhD](/media/14022906/68-besse.jpg)
Benjamin Besse, MD, PhD
Unfortunately, toxicity appeared to be additive and may be synergistic for some conditions,” Dr. Besse noted. Compared with previously reported rates for amivantamab as a single agent, increased rates were observed for rash, paronychia, stomatitis, diarrhea, and peripheral edema; 42% of patients experienced treatment interruptions and 15% had treatment discontinued because of adverse events. “Amivantamab is not a completely easy drug to give, and we have to manage patients aggressively. Infusion-site reactions were common with the first cycle, but with the subcutaneous form being developed, this should no longer be a problem,” he noted.
Finally, Dr. Besse questioned whether amivantamab needs to be given with chemotherapy, based on the efficacy shown as a single agent in the phase I CHRYSALIS study.1 In this trial of heavily pretreated patients, the response rate was 40%, median progression-free survival was 8.3 months, and median overall survival was 23 months. However, in subsequent follow-up, the outcomes were less impressive. “It was wise to combine amivantamab with chemotherapy,” he concluded.
“Can we do better? Yes, if we find a predictive factor,” Dr. Besse suggested. Exon 20 insertion location and absence of baseline RAS/RAF/MEK alterations might qualify as biomarkers of response, he added.
Meanwhile, amivantamab may fill a niche for this 1% to 3% of patients who have not had satisfactory responses with any other available or experimental agent. “Osimertinib is very potent against classical EGFR mutations—exons 19 and 21—but exon 20 is a different story,” Dr. Besse said.
DISCLOSURE: Dr. Besse reported personal financial relationships with AbbVie, Amgen, AstraZeneca, Chugai, Daiichi Sankyo, Ellipse Pharma, Eisai, GenMab, Genzyme, Hedera Dx, Inivata, Ipsen, Janssen, MSD, PharmaMar, Roche-Genentech, Sanofi, Socar Research, Tahio Oncology, and Turning.
REFERENCE
1. Park K, Haura EB, Leighl NB, et al: Amivantamab in EGFR exon 20 insertion-mutated non-small-cell lung cancer progressing on platinum chemotherapy: Initial results from the CHRYSALIS phase I study. J Clin Oncol 39:3391-3402, 2021.