Authors' objectives: Non-small cell lung cancer (NSCLC) is the most common lung cancer subtype and carries a poor prognosis, with 5-year survival around 4% in metastatic disease. EGFR mutations are the most clinically relevant driver alterations, present in roughly 11% of Austrian NSCLC cases. Two guideline-recommended first-line options for advanced NSCLC with common EGFR mutations (exon 19 deletions, exon 21 L858R) are amivantamab (intravenous or subcutaneous) plus lazertinib, and osimertinib plus platinum-based chemotherapy. This report assesses their comparative effectiveness, safety, and economic and organisational implications, including intravenous versus subcutaneous administration.

Authors' results and conclusions: Clinical results: As no head-to-head trial comparing the two regimens was available, three indirect treatment comparisons (ITCs) were identified, two of which were part of the NICE and CDA-AMC HTA reports. Given limitations of the indirect evidence, the underlying pivotal phase 3 trials MARIPOSA (amivantamab plus lazertinib) and FLAURA2 (osimertinib plus chemotherapy), each comparing the respective combination with osimertinib monotherapy, were also considered descriptively, alongside one supportive single-arm study. Both regimens showed significant overall survival (OS) and progression-free survival benefits over osimertinib monotherapy in their respective pivotal trials with high response rates (83–86%). Direct comparison remains uncertain: MARIPOSA's median OS (amivantamab plus lazertinib) had not yet been reached versus FLAURA2's mature median (osimertinib plus chemotherapy). The ITCs reached differing conclusions, reflecting differences in methodology and underlying trials, and neither HTA report considered the indirect evidence sufficiently to resolve efficacy uncertainty. Grade ≥3 adverse events were frequent with both regimens but differed qualitatively: skin toxicity and venous thromboembolism (VTE) with amivantamab plus lazertinib, myelosuppression with osimertinib plus chemotherapy. Quality-of-life data were absent from both trials. Subcutaneous amivantamab was non-inferior to intravenous administration for objective response, with fewer infusion-related reactions and VTE events and improved patient-reported outcomes. Conclusion: Available evidence suggests no clear efficacy advantage of either regimen over the other, though the absence of direct comparative data leaves true differences uncertain. Safety profiles differ qualitatively rather than in overall burden. In Austria, amivantamab plus lazertinib entails substantially higher costs and organisational demands, only partly mitigated by the subcutaneous formulation.

Authors' recommendations: Treatment decisions should consider costs, toxicity, organisational feasibility, and patient preferences. Registry data could help address remaining evidence gaps.

Authors' methods: A systematic search covered Medline, Embase, the Cochrane Library and the HTA Database (INAHTA), supplemented by hand searching, with independent dual screening and extraction. Risk of bias in randomised controlled trials was assessed using Cochrane RoB v.2. An Austrian budget impact analysis used ex-factory prices and hospital cost data. Organisational aspects were synthesised narratively from the literature and expert consultation.

Project Status: Completed

URL for project: https://aihta.at/en/annual-research-programmes/annual-research-programme-2026/amivantamab-plus-lazertinib-vs-osimertinib-plus-chemotherapy-in-the-first-line-treatment-of-advanced-non-small-cell-lung-cancer

Year Published: 2026

URL for published report: https://eprints.aihta.at/1622/1/HTA-Projektbericht_Nr.184.pdf

URL for additional information: https://eprints.aihta.at/1622/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Austria

Organisation Name: Austrian Institute for Health Technology Assessment

Contact Address: Josefstaedter Strasse 39, A-1080 Vienna, Austria

Contact Name: office@aihta.at

Contact Email: office@aihta.at