ISPOR 2025
Tuesday, May 13 - Friday, May 16
Taletrectinib vs Entrectinib in ROS1-Positive (ROS1+) Non-Small Cell Lung Cancer (NSCLC): A Matching-Adjusted Indirect Comparison (MAIC)
Author(s)
Misako Nagasaka, MD, PhD1, Geoffrey Liu, MSc, MD2, Nathan A. Pennell, PhD, MD3, Maurice Pérol, MD4, Wenfeng Chen, MD5, Lyudmila Bazhenova, MD6, Caicun Zhou, MD7;
1University of California Irvine School of Medicine and Chao Family Comprehensive Cancer Center, Orange, CA, USA, 2Princess Margaret Cancer Centre, Temerty School of Medicine, University of Toronto, Toronto, ON, Canada, 3Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA, 4Léon Bérard Cancer Center, Lyon, France, 5Nuvation Bio, New York, NY, USA, 6University of California San Diego Moores Cancer Center, San Diego, CA, USA, 7Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China
1University of California Irvine School of Medicine and Chao Family Comprehensive Cancer Center, Orange, CA, USA, 2Princess Margaret Cancer Centre, Temerty School of Medicine, University of Toronto, Toronto, ON, Canada, 3Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA, 4Léon Bérard Cancer Center, Lyon, France, 5Nuvation Bio, New York, NY, USA, 6University of California San Diego Moores Cancer Center, San Diego, CA, USA, 7Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China
Presentation Documents
OBJECTIVES: We compared taletrectinib, a highly potent, next-generation, selective central nervous system (CNS)-active ROS1-positive (ROS1+) tyrosine kinase inhibitor (TKI), with entrectinib, a TKI with perceived CNS activity. In the absence of head-to-head trials, our analysis utilized a matching-adjusted indirect comparison (MAIC) to focus on TKI-naive patients with ROS1+ non-small cell lung cancer (NSCLC).
METHODS: Pooled patient data for taletrectinib were obtained from the TRUST-I (NCT04395677) and TRUST-II (NCT04919811) studies, with a data cutoff of June 2024. These patients were matched to patients receiving entrectinib in the ALKA-372-001 (EudraCT 2012-000148-88), STARTRK-1 (NCT02097810), and STARTRK-2 (NCT02568267) studies on gender, ECOG status, smoking history, histological classification, baseline CNS disease, and number of previous systemic therapies. Objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using adjusted Cox regression models.
RESULTS: The covariates were balanced between the taletrectinib and entrectinib groups after matching. The ORR was significantly higher for taletrectinib (N=89; 87.6% [95% CI: 79.0%-93.7%]) than for entrectinib (N=161; 67.1% [95% CI: 59.2%-74.3%]) as the 95% CIs did not overlap. The HRs for DOR demonstrated a significant improvement in the likelihood of maintaining a response with taletrectinib vs entrectinib (0.35 [95% CI: 0.208-0.598]). Patients treated with taletrectinib experienced a significant 58% reduction in the rate of disease progression vs those treated with entrectinib (HR for PFS: 0.42 [95% CI: 0.274-0.649]).
CONCLUSIONS: Taletrectinib showed significantly improved outcomes vs entrectinib in TKI-naive patients with ROS1+ NSCLC in the cross-trial MAIC analysis, including higher ORR and substantially reduced rate of progression. Additional analyses with more mature DOR and PFS data, along with a comparative analysis of safety outcomes, will provide a comprehensive benefit-risk assessment.
METHODS: Pooled patient data for taletrectinib were obtained from the TRUST-I (NCT04395677) and TRUST-II (NCT04919811) studies, with a data cutoff of June 2024. These patients were matched to patients receiving entrectinib in the ALKA-372-001 (EudraCT 2012-000148-88), STARTRK-1 (NCT02097810), and STARTRK-2 (NCT02568267) studies on gender, ECOG status, smoking history, histological classification, baseline CNS disease, and number of previous systemic therapies. Objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using adjusted Cox regression models.
RESULTS: The covariates were balanced between the taletrectinib and entrectinib groups after matching. The ORR was significantly higher for taletrectinib (N=89; 87.6% [95% CI: 79.0%-93.7%]) than for entrectinib (N=161; 67.1% [95% CI: 59.2%-74.3%]) as the 95% CIs did not overlap. The HRs for DOR demonstrated a significant improvement in the likelihood of maintaining a response with taletrectinib vs entrectinib (0.35 [95% CI: 0.208-0.598]). Patients treated with taletrectinib experienced a significant 58% reduction in the rate of disease progression vs those treated with entrectinib (HR for PFS: 0.42 [95% CI: 0.274-0.649]).
CONCLUSIONS: Taletrectinib showed significantly improved outcomes vs entrectinib in TKI-naive patients with ROS1+ NSCLC in the cross-trial MAIC analysis, including higher ORR and substantially reduced rate of progression. Additional analyses with more mature DOR and PFS data, along with a comparative analysis of safety outcomes, will provide a comprehensive benefit-risk assessment.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO151
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment, Comparative Effectiveness or Efficacy
Disease
SDC: Oncology