Switching to SC Dosing and Considering PRO Data for Amivantamab in NSCLC

Chul Kim, MD, MPH, director of Thoracic Oncology at MedStar Georgetown University Hospital, and associate professor at Georgetown University, discussed safety and quality-of-life findings from the phase 3 PAPILLON trial (NCT04538664) assessing amivantamab-vmjw (Rybrevant) plus chemotherapy in EGFR exon 20 insertion mutation–positive non–small cell lung cancer (NSCLC) that he presented at the IASLC 2026 World Conference on Lung Cancer (WCLC).¹ Paronychia, rash, and infusion-related reactions were common with intravenous amivantamab in the PAPILLON trial.

Kim highlighted how prophylactic strategies studied in the phase 2 COCOON (NCT06120140) and SKIPPirr trials (NCT05663866), together with a shift toward subcutaneous amivantamab (Rybrevant Faspro) dosing, are changing the agent’s safety profile in practice.^2,3 He also explained why patient-reported outcomes, including delayed time to worsening of pain and dyspnea, matter clinically regardless of where survival data land statistically.

Transcript:

Paronychia, rash, and infusion-related reactions were common with intravenous amivantamab in PAPILLON. Now that the subcutaneous formulation is available, and with updated findings from phase 3 PALOMA-2 (NCT01740427) and phase 2b COPERNICUS (NCT06667076) also being presented at WCLC, how do you see the field moving away from the safety profile seen here?

Kim: PAPILLON was conducted prior to prophylactic strategies such as the COCOON and SKIPPirr trials. With COCOON, we’ve seen a big improvement in dermatologic complications, and the field has largely shifted toward use of subcutaneous amivantamab. In my own practice, when I use amivantamab, I favor the subcutaneous formulation over intravenous amivantamab because it reduces infusion-related reactions quite significantly. It’s my practice to use subcutaneous amivantamab even in the setting of the PAPILLON regimen, and many of my colleagues do the same. There’s also a benefit in chair time; subcutaneous administration is a lot shorter than intravenous. There are a lot of benefits to using subcutaneous amivantamab.

Your presentation also covered patient-reported outcomes. How much do those quality-of-life data matter to you clinically regardless of where outcomes like overall survival may land statistically?

It’s important to understand what patients experience during treatment. In this patient-reported outcome analysis, we used the EORTC QLQ-C30 instrument, which we use a lot, and what was shown was that time to worsening of symptoms was improved with amivantamab plus chemotherapy compared with chemotherapy alone. That was seen across multiple domains, including important symptoms like pain and dyspnea, which patients with lung cancer frequently experience. We see improvement in those domains, which is encouraging. It’s important to see the survival data, but we also have to understand what patients experience with the treatment. That’s an important aspect of trial outcomes reporting.

References

1. Kim C, Tang K-J, Cho BC, et al. First-line amivantamab-chemotherapy vs chemotherapy in EGFR exon 20 insertion-mutated non-small cell lung cancer: overall survival from PAPILLON. Presented at: 2026 World Conference on Lung Cancer; September 12-15, 2026; Seoul, South Korea. Abstract PL03.03.
2. Cho BC, Li W, Spira AI, et al. Enhanced versus standard dermatologic management with amivantamab-lazertinib in EGFR-mutated advanced NSCLC: the COCOON global randomized controlled trial. J Thorac Oncol. 2025;20(9):1517-1530. doi:10.1016/j.jtho.2025.07.117
3. Spira AI, Paz-Ares L, Han JY, et al. Preventing infusion-related reactions with intravenous amivantamab: results from SKIPPirr, a phase 2 study: a brief report. J Thorac Oncol. 2025;20(6):809-816. doi:10.1016/j.jtho.2025.01.018