US Population-Level Clinical Impact of Lorlatinib Treatment on ALK+ Metastatic Non-Small Cell Lung Cancer Outcomes
Author(s)
Adam Kasle, BA1, Devin Abrahami, PhD2, David Veenstra, PharmD, PhD1, Robert Morlock, PhD3, Krishnan Ramaswamy, PhD2, Priya Ramachandran, PharmD, MBA2, Lindsay Stansfield, PharmD, BCOP, BCPS2, Sean D. Sullivan, PhD4, Raymond Mak, MD5.
1Curta, Seattle, WA, USA, 2Pfizer, New York, NY, USA, 3Acumen Health Research Institute, White Lake, MI, USA, 4University of Washington, Seattle, WA, USA, 5Mass General Brigham, Boston, MA, USA.
1Curta, Seattle, WA, USA, 2Pfizer, New York, NY, USA, 3Acumen Health Research Institute, White Lake, MI, USA, 4University of Washington, Seattle, WA, USA, 5Mass General Brigham, Boston, MA, USA.
OBJECTIVES: Lorlatinib demonstrated significantly and substantially prolonged progression-free survival (PFS) over crizotinib for patients with previously untreated advanced ALK-positive non-small cell lung cancer (NSCLC) in the Phase 3 CROWN study. In the 5-year update, median PFS had not yet been reached, with 60% and 92% of patients progression-free and without intracranial progression in the lorlatinib arm, respectively, compared to 8% and 21% in the crizotinib arm. Based on the updated CROWN analysis, we estimated the population-level clinical impact of lorlatinib vs alectinib.
METHODS: We developed a decision-analytic model comparing a scenario with lorlatinib use in first-line vs a scenario without lorlatinib in first-line. We used three-state partitioned survival model (pre-progression, post-progression, and death) to project clinical outcomes. Lorlatinib-eligible population estimates were derived from published literature and market research; treatment effectiveness for lorlatinib was derived from CROWN data, while comparative effectiveness for alectinib was informed using a match-adjusted indirect comparison based on the ALEX study. Intracranial progression was modeled as an intercurrent event to capture the incidence of brain metastases (BM) for patients on first-line treatment. Key scenarios included using different PFS extrapolations, assuming 100% lorlatinib uptake and applying risk of BM post-discontinuation.
RESULTS: We estimated that a cohort of 3,100 patients in the US would be eligible for lorlatinib in 2025. Compared to no lorlatinib use, lorlatinib treatment resulted in 1,620-5,170 and 1,590-4,880 more life-years (LYs) and quality-adjusted life-years (QALYs), respectively over a 20-year time horizon across scenarios. Per-patient incidence of BM ranged from 0.14-0.18 and 0.21-0.40 for lorlatinib and alectinib, respectively, resulting in 68-256 BMs avoided. Separately, 5-14 patients were needed to be treated to avoid a BM.
CONCLUSIONS: Lorlatinib treatment results in fewer BMs, and more LYs and QALYs vs alectinib in first-line advanced ALK-positive NSCLC, suggesting there is substantial clinical value in lorlatinib treatment in this population.
METHODS: We developed a decision-analytic model comparing a scenario with lorlatinib use in first-line vs a scenario without lorlatinib in first-line. We used three-state partitioned survival model (pre-progression, post-progression, and death) to project clinical outcomes. Lorlatinib-eligible population estimates were derived from published literature and market research; treatment effectiveness for lorlatinib was derived from CROWN data, while comparative effectiveness for alectinib was informed using a match-adjusted indirect comparison based on the ALEX study. Intracranial progression was modeled as an intercurrent event to capture the incidence of brain metastases (BM) for patients on first-line treatment. Key scenarios included using different PFS extrapolations, assuming 100% lorlatinib uptake and applying risk of BM post-discontinuation.
RESULTS: We estimated that a cohort of 3,100 patients in the US would be eligible for lorlatinib in 2025. Compared to no lorlatinib use, lorlatinib treatment resulted in 1,620-5,170 and 1,590-4,880 more life-years (LYs) and quality-adjusted life-years (QALYs), respectively over a 20-year time horizon across scenarios. Per-patient incidence of BM ranged from 0.14-0.18 and 0.21-0.40 for lorlatinib and alectinib, respectively, resulting in 68-256 BMs avoided. Separately, 5-14 patients were needed to be treated to avoid a BM.
CONCLUSIONS: Lorlatinib treatment results in fewer BMs, and more LYs and QALYs vs alectinib in first-line advanced ALK-positive NSCLC, suggesting there is substantial clinical value in lorlatinib treatment in this population.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO258
Topic
Clinical Outcomes, Economic Evaluation, Epidemiology & Public Health
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Oncology