Clinical Efficacy and Safety of Targeted Therapies for HER2 Mutant Advanced or Metastatic Non-Small Cell Lung Cancer: A Systematic Literature Review
Author(s)
Federico Manevy, MSc1, Pawana Sharma, MSc2, Noman Paracha, MSc1, kostas papadakis, MBA1, Vadim Bernard-Gauthier, PhD3, Ritu Gupta, MSc4, Xuan Wang, MD. MSc5.
1Bayer Consumer Care AG, Basel, Switzerland, 2ICON plc, Birmingham, United Kingdom, 3Bayer Canadian Holdings Inc., Toronto, ON, Canada, 4ICON plc, Delhi, India, 5ICON plc, Stockholm, Sweden.
1Bayer Consumer Care AG, Basel, Switzerland, 2ICON plc, Birmingham, United Kingdom, 3Bayer Canadian Holdings Inc., Toronto, ON, Canada, 4ICON plc, Delhi, India, 5ICON plc, Stockholm, Sweden.
OBJECTIVES: HER2 mutations occur in 2-4% of non-small cell lung cancer (NSCLC) cases, particularly adenocarcinomas. Emerging evidence suggests patients with HER2-mutant NSCLC may respond less favorably to anti-cancer therapies. This review summarizes clinical outcomes reported for treatments in advanced or metastatic HER2-mutant NSCLC.
METHODS: MEDLINE, EMBASE, Cochrane CENTRAL, and CDSR were searched on September 5, 2024, for clinical trials reporting efficacy, safety, and quality of life (QoL) in HER2-mutant advanced NSCLC. No limits were placed on date or geographic region. Additional sources included clinical trial registries (from 2023 onward) and conference abstracts from 2023-2024 (ASCO, ESMO, IASLC, and ELCC). (PROSPERO registration: CRD42024591639.)
RESULTS: A total of 58 publications (41 trials) were included. Most (n=35) were single-arm; three were multi-arm; and three were multicohort, evaluating different doses of the same treatment. Seven were phase I, two phase I/II, and 29 phase II - of which 20 prioritized objective response rate (ORR) as the primary endpoint. Nineteen trials reported HER2-mutant results as a subset of broader NSCLC populations. Only two trials - both on pyrotinib - used progression-free survival (PFS) as the primary outcome and included HER2-mutated and/or HER2-amplified metastatic NSCLC. Among studies reporting race, most enrolled predominantly East Asian patients, with 12 conducted exclusively in East Asia. Most trials evaluated HER2 tyrosine kinase inhibitors (TKIs; n=19), followed by antibody-drug conjugates (ADCs; n=9). Due to substantial heterogeneity in study design and patient characteristics, outcomes varied widely: PFS ranged from 2.76 (95% CI: 1.87-4.60) to 15.4 months (95% CI: 8.3-not estimable); overall survival (OS) 8.1 to 19 months; ORR 0% to 74%; and disease control rate (DCR) 38% to 100%. Only two trials reported QoL outcomes.
CONCLUSIONS: HER2-targeted therapies in advanced NSCLC have shown potential for rapid and durable responses in HER2-mutant populations, though efficacy varies considerably and comparative evidence remains limited.
METHODS: MEDLINE, EMBASE, Cochrane CENTRAL, and CDSR were searched on September 5, 2024, for clinical trials reporting efficacy, safety, and quality of life (QoL) in HER2-mutant advanced NSCLC. No limits were placed on date or geographic region. Additional sources included clinical trial registries (from 2023 onward) and conference abstracts from 2023-2024 (ASCO, ESMO, IASLC, and ELCC). (PROSPERO registration: CRD42024591639.)
RESULTS: A total of 58 publications (41 trials) were included. Most (n=35) were single-arm; three were multi-arm; and three were multicohort, evaluating different doses of the same treatment. Seven were phase I, two phase I/II, and 29 phase II - of which 20 prioritized objective response rate (ORR) as the primary endpoint. Nineteen trials reported HER2-mutant results as a subset of broader NSCLC populations. Only two trials - both on pyrotinib - used progression-free survival (PFS) as the primary outcome and included HER2-mutated and/or HER2-amplified metastatic NSCLC. Among studies reporting race, most enrolled predominantly East Asian patients, with 12 conducted exclusively in East Asia. Most trials evaluated HER2 tyrosine kinase inhibitors (TKIs; n=19), followed by antibody-drug conjugates (ADCs; n=9). Due to substantial heterogeneity in study design and patient characteristics, outcomes varied widely: PFS ranged from 2.76 (95% CI: 1.87-4.60) to 15.4 months (95% CI: 8.3-not estimable); overall survival (OS) 8.1 to 19 months; ORR 0% to 74%; and disease control rate (DCR) 38% to 100%. Only two trials reported QoL outcomes.
CONCLUSIONS: HER2-targeted therapies in advanced NSCLC have shown potential for rapid and durable responses in HER2-mutant populations, though efficacy varies considerably and comparative evidence remains limited.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO45
Topic
Clinical Outcomes
Disease
Oncology