“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

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.