Subcutaneous amivantamab non-inferior and more convenient than intravenous amivantamab

Compared with intravenous amivantamab, subcutaneous amivantamab demonstrated a non-inferior efficacy while improving patient satisfaction in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) who progressed on or after osimertinib and chemotherapy in the PALOMA-3 trial.

Amivantamab is an EGFR-MET bispecific antibody approved for use in intravenous formulation. However, intravenous administration lasts more than 4 hours and comes with an infusion-related reaction (IRR) rate of 67% [1]. The phase 3 PALOMA-3 trial (NCT05388669) evaluated subcutaneous versus intravenous amivantamab in 418 patients with EGFR-mutated NSCLC who had progressed on or after osimertinib and platinum-based chemotherapy. Participants were 1:1 randomised to receive subcutaneous amivantamab (plus lazertinib) versus intravenous amivantamab (plus lazertinib). Dr Natasha Leighl (Princess Margaret Cancer Centre, Canada) presented the results [2].

The pharmacokinetic primary endpoints (C_trough at cycle 2, day 1; cycle 2 AUC_day1-15) were not different between the treatment arms, meeting non-inferiority criteria. Objective response rate was also non-inferior between subcutaneous and intravenous treatment.

Subcutaneous amivantamab administration was associated with numerically improved median duration of response (11.2 vs 8.3 months) and progression-free survival (6.1 vs 4.3 months; HR 0.84; 95% CI 0.64–1.10; P=0.20). The exploratory endpoint of overall survival was significantly improved in the subcutaneous arm (HR 0.62; 95% CI 0.42–0.92; P=0.02).

The incidence of IRR-related symptoms was significantly lower in the subcutaneous arm (13% vs 66%), as was the incidence of venous thromboembolism (9% vs 14%). The administration time of subcutaneous amivantamab was significantly shorter (less than 5 minutes vs 2–5 hours), whereas the frequency of patient-reported convenience was significantly higher (85% vs 52%).

Based on these results, Dr Leighl concluded that “subcutaneous amivantamab demonstrated non-inferior efficacy, lower rates of IRR, and more convenience for patients and providers compared with intravenous amivantamab.”

1. Park K, et al. Lung Cancer 2023;178:166-171.
2. Leighl NB, et al. Subcutaneous amivantamab vs intravenous amivantamab, both in combination with lazertinib, in refractory EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results, including overall survival (OS), from the global, phase 3, randomized controlled PALOMA-3 trial. Abstract LBA8505, ASCO Annual Meeting 2024, 31 May–4 June, Chicago, IL, USA.

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Posted on 18 July 202418 July 2024