Quality-Adjusted Time Without Symptoms or Toxicity Q-TWiST Estimates in Previously Treated HER2-Positive Biliary Tract Carcinoma (BTC) Using the Zanidatamab HERIZON-BTC-01 Study
Author(s)
Will Battershill, MSc1, Anthony Hatswell, PhD1, Kurt Taylor, PhD1, Javier Sabater, B.Pharm2, Sally Bowditch, BSc, MPH2, Junji Lin, PhD3, Phillip Garfin, MD, PhD4, Xiaotian Wu, MSc3, Wayne Su, MSc3, John Bridgewater, PhD5.
1Petauri Evidence Ltd, Nottingham, United Kingdom, 2Jazz Pharmaceuticals, Oxford, United Kingdom, 3Jazz Pharmaceuticals, Philadelphia, PA, USA, 4Jazz Pharmaceuticals, Palo Alto, CA, USA, 5University College London Cancer Institute, London, United Kingdom.
1Petauri Evidence Ltd, Nottingham, United Kingdom, 2Jazz Pharmaceuticals, Oxford, United Kingdom, 3Jazz Pharmaceuticals, Philadelphia, PA, USA, 4Jazz Pharmaceuticals, Palo Alto, CA, USA, 5University College London Cancer Institute, London, United Kingdom.
OBJECTIVES: BTCs are rare, diverse tumours often diagnosed at an advanced stage. Following relapse, patients have a poor prognosis and few treatment options. Zanidatamab demonstrated clinical benefit and manageable safety in treatment-refractory HER2-positive BTC in the phase 2 HERIZON-BTC-01 single-arm trial. The objective of this research was to perform a Q-TWiST analysis of zanidatamab to jointly evaluate survival time and quality of life. To the authors’ knowledge, based on a targeted literature review, this is the first Q-TWiST analysis in an uncontrolled BTC trial.
METHODS: Patient survival time was partitioned into three health states: time without symptoms of disease or significant toxicity (TWiST), time with treatment-related toxicity (TOX, defined as ≥1 grade ≥3 adverse event [AE]), and time following disease progression (REL). To calculate these, Kaplan-Meier analysis was performed and restricted mean survival time (RMST) was estimated for AE duration, overall survival (OS), and progression-free survival (PFS). The TOX RMST was adjusted by scaling to the proportion (40/87) of patients with observed TOX. TWiST duration was derived as PFS minus adjusted TOX. REL duration was derived as OS minus PFS. Q-TWiST was calculated using standard weights: 1 for TWiST, 0.5 for TOX and REL. Uncertainty was assessed using 1,000 bootstrap samples.
RESULTS: RMST was 16.57 months for OS, 9.90 months for PFS, and 0.60 months for adjusted TOX (1.32 months unadjusted). Mean health state durations following bootstrapping were 0.60 (95% confidence interval [CI]: 0.32, 0.98) for TOX, 9.18 (95% CI: 6.77, 11.73) for TWiST, and 6.77 (95% CI: 4.61, 9.13) for REL. The resulting Q-TWiST estimate for zanidatamab using HERIZON-BTC-01 trial data was 12.87 months (95% CI: 10.53, 15.17).
CONCLUSIONS: Considerably more PFS time was spent in the TWiST state than TOX state, highlighting zanidatamab’s manageable safety profile. Longer TWiST duration than REL suggests Q-TWiST was primarily driven by TWiST, reflecting notable symptom-free survival.
METHODS: Patient survival time was partitioned into three health states: time without symptoms of disease or significant toxicity (TWiST), time with treatment-related toxicity (TOX, defined as ≥1 grade ≥3 adverse event [AE]), and time following disease progression (REL). To calculate these, Kaplan-Meier analysis was performed and restricted mean survival time (RMST) was estimated for AE duration, overall survival (OS), and progression-free survival (PFS). The TOX RMST was adjusted by scaling to the proportion (40/87) of patients with observed TOX. TWiST duration was derived as PFS minus adjusted TOX. REL duration was derived as OS minus PFS. Q-TWiST was calculated using standard weights: 1 for TWiST, 0.5 for TOX and REL. Uncertainty was assessed using 1,000 bootstrap samples.
RESULTS: RMST was 16.57 months for OS, 9.90 months for PFS, and 0.60 months for adjusted TOX (1.32 months unadjusted). Mean health state durations following bootstrapping were 0.60 (95% confidence interval [CI]: 0.32, 0.98) for TOX, 9.18 (95% CI: 6.77, 11.73) for TWiST, and 6.77 (95% CI: 4.61, 9.13) for REL. The resulting Q-TWiST estimate for zanidatamab using HERIZON-BTC-01 trial data was 12.87 months (95% CI: 10.53, 15.17).
CONCLUSIONS: Considerably more PFS time was spent in the TWiST state than TOX state, highlighting zanidatamab’s manageable safety profile. Longer TWiST duration than REL suggests Q-TWiST was primarily driven by TWiST, reflecting notable symptom-free survival.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
PCR203
Topic
Patient-Centered Research
Topic Subcategory
Health State Utilities, Patient-reported Outcomes & Quality of Life Outcomes
Disease
Gastrointestinal Disorders, Oncology