Efficacy and Safety of Antibody-Drug Conjugates (ADCs) in Pretreated Locally Advanced/Metastatic (LA/m) Non-Small Cell Lung Cancer (NSCLC): A Systematic Literature Review (SLR)
Author(s)
Patricia Dorling, MS, PharmD, PhD1, Shalini Bagga, PhD2, Vaneet Kaur Khurana, MPH3, Prashant Soni, PhD4, Alifiya Rounak, PhD5, Ridhi Babel, PhD1, Tanya Keenan, MD1.
1Merck & Co, Rahway, NJ, USA, 2CHEORS powered by BioBridges, North Wales, PA, USA, 3CHEORS, Cambridge, ON, Canada, 4CHEORS, Delhi, India, 5CHEORS, North Wales, PA, USA.
1Merck & Co, Rahway, NJ, USA, 2CHEORS powered by BioBridges, North Wales, PA, USA, 3CHEORS, Cambridge, ON, Canada, 4CHEORS, Delhi, India, 5CHEORS, North Wales, PA, USA.
OBJECTIVES: ADCs represent a novel therapeutic class designed to deliver cytotoxic agents directly to cancer cells, with the goal of conferring greater clinical benefits and reduced systemic toxicity compared to conventional chemotherapy. This SLR assessed safety & efficacy of ADCs in LA/m NSCLC patients previously treated with systemic anti-cancer therapy.
METHODS: This SLR was conducted using Cochrane’s methodology. Searches performed in MEDLINE, Embase, Cochrane covering last 10 yrs, and supplemented with trial registries and conference proceedings.
RESULTS: 11 ADC trials in NSCLC patients were identified. Three PhII trials evaluated trastuzumab deruxtecan in patients with HER2 altered tumors (DESTINY-Lung01, DESTINY-Lung02 and DESTINY-Lung05) with objective response rate (ORR) ranging from 50-58%. Safety varied by dose - patients in 5.4mg/kg arm had fewer grade≥3 treatment related adverse events (TRAEs) (40-51%) vs 6.4mg/kg arm (53-60%), with AE-related discontinuations of 15-17% vs 26-27% respectively. Two PhII (TROPION-Lung05 and ICARUS-LUNG01) and one PhIII (TROPION-Lung01) trial evaluated datopotamab deruxtecan in patients with various genomic profiles. Median progression-free survival (mPFS) ranged from 3.5-4.4 months, ORR from 26-36%. Grade≥3 TRAEs were 26% in TROPION-Lung01, with discontinuation rate of 10% in TROPION-Lung05. Sacituzumab govitecan monotherapy (EVOKE-01, PhIII) numerically approved mPFS (4.1 vs 3.9 months) with fewer grade ≥3 TRAEs (52 vs 60%) and lower AE-related discontinuation (10 vs 17%) vs docetaxel. Trastuzumab emtansine (T-DM1) showed limited efficacy both as monotherapy in HER2 positive NSCLC and in combination with Osimertinib in EGFR-mutated NSCLC with HER2 overexpression. Across three PhII trials, mPFS with T-DM1 was 2-2.8 months, with 15% grade ≥3 TRAEs, and 4-15% discontinuation rate due to AEs.
CONCLUSIONS: ADCs demonstrated promising clinical activity in pretreated NSCLC, particularly in biomarker-selected populations, and showed manageable safety profiles. These findings support the growing role of ADCs in NSCLC treatment sequencing and may inform payer decisions regarding value, access, and future economic evaluations.
METHODS: This SLR was conducted using Cochrane’s methodology. Searches performed in MEDLINE, Embase, Cochrane covering last 10 yrs, and supplemented with trial registries and conference proceedings.
RESULTS: 11 ADC trials in NSCLC patients were identified. Three PhII trials evaluated trastuzumab deruxtecan in patients with HER2 altered tumors (DESTINY-Lung01, DESTINY-Lung02 and DESTINY-Lung05) with objective response rate (ORR) ranging from 50-58%. Safety varied by dose - patients in 5.4mg/kg arm had fewer grade≥3 treatment related adverse events (TRAEs) (40-51%) vs 6.4mg/kg arm (53-60%), with AE-related discontinuations of 15-17% vs 26-27% respectively. Two PhII (TROPION-Lung05 and ICARUS-LUNG01) and one PhIII (TROPION-Lung01) trial evaluated datopotamab deruxtecan in patients with various genomic profiles. Median progression-free survival (mPFS) ranged from 3.5-4.4 months, ORR from 26-36%. Grade≥3 TRAEs were 26% in TROPION-Lung01, with discontinuation rate of 10% in TROPION-Lung05. Sacituzumab govitecan monotherapy (EVOKE-01, PhIII) numerically approved mPFS (4.1 vs 3.9 months) with fewer grade ≥3 TRAEs (52 vs 60%) and lower AE-related discontinuation (10 vs 17%) vs docetaxel. Trastuzumab emtansine (T-DM1) showed limited efficacy both as monotherapy in HER2 positive NSCLC and in combination with Osimertinib in EGFR-mutated NSCLC with HER2 overexpression. Across three PhII trials, mPFS with T-DM1 was 2-2.8 months, with 15% grade ≥3 TRAEs, and 4-15% discontinuation rate due to AEs.
CONCLUSIONS: ADCs demonstrated promising clinical activity in pretreated NSCLC, particularly in biomarker-selected populations, and showed manageable safety profiles. These findings support the growing role of ADCs in NSCLC treatment sequencing and may inform payer decisions regarding value, access, and future economic evaluations.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO90
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Oncology