The phase 2 PALOMA-2 trial (NCT05498428) evaluated subcutaneous amivantamab (Rybrevant Faspro) plus lazertinib (Lazcluze) in patients with treatment-naive, EGFR-mutated advanced non-small cell lung cancer (NSCLC). Updated data presented at the IASLC 2026 World Conference on Lung Cancer (WCLC) showed a 3-year overall survival rate of 70% across cohorts 1, 5, and 6 of the study.1 By comparison, the phase 3 MARIPOSA trial (NCT04487080) reported a 3-year overall survival rate of 60% with intravenous amivantamab plus lazertinib vs 51% with osimertinib (Tagrisso) alone (HR, 0.75; 95% CI, 0.61-0.92; P = .005).2
Misako Nagasaka, MD, PhD, an associate clinical professor in the Division of Hematology/Oncology at the University of California, Irvine (UCI), who presented the PALOMA-2 data at WCLC, spoke with CancerNetwork® about how clinicians should interpret this cross-trial comparison without overselling the difference between the subcutaneous and intravenous regimens.
Editor’s Note: Nagasaka declares that her personal opinions/thoughts are hers and not those of UCI Health, UC Regents, and any other related entities.
Transcript:
CancerNetwork: Findings from PALOMA-2 compare favorably with historical OS outcomes from MARIPOSA. How should clinicians interpret cross-trial, non-randomized comparisons like that without overselling the difference between subcutaneous and intravenous amivantamab?
Nagasaka: Cross-trial comparisons are always going to be challenging, especially with PALOMA-2, [as] we do not have a control group. But we know from PALOMA-3 [NCT05388669], which was a study where patients who had already progressed on osimertinib and chemotherapy were randomly [assigned] to receive either subcutaneous amivantamab plus lazertinib or intravenous amivantamab plus lazertinib, that in that setting we saw a better safety profile with amivantamab given subcutaneously, and also signs of improved efficacy outcomes based on hazard ratios from that study.3
Right now, as the data mature, it’s certainly looking promising; we’re seeing an overall survival [rate] at 3 years, with PALOMA-2, of 70%, whereas that number was 60% with MARIPOSA, the intravenous amivantamab regimen. I think we’re seeing consistent messages from these trials that amivantamab given subcutaneously appears to have a better tolerability profile, a better safety profile, and even though we’re giving it less frequently than intravenously, that is not giving any detrimental effects to efficacy outcomes. If anything, the outcomes may look better compared with the intravenous formulation, and I think that’s really promising. It gives us comfort to be able to really pursue the subcutaneous amivantamab route because that is much safer and convenient for patients.
References
- Nagasaka M, Dias JM, Tan J-L, et al. First-line subcutaneous amivantamab plus lazertinib in EGFR-mutated advanced NSCLC: updated results from the PALOMA-2 study. Presented at: 2026 World Conference on Lung Cancer; September 12-15, 2026; Seoul, South Korea. Abstract PT2.03.06.
- Yang JC, Lu S, Hayashi H, et al. Overall survival with amivantamab-lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med. 2025;393(17):1681-1693. doi:10.1056/NEJMoa2503001
- Leighl NB, Akamatsu H, Lim SM, et al. Subcutaneous versus intravenous amivantamab, both in combination with lazertinib, in refractory EGFR-mutated non-small cell lung cancer: primary results from the phase III PALOMA-3 study. J Clin Oncol. 2024;42(30):3593-3605. doi:10.1200/JCO.24.01001
