Cost-Effectiveness of First-Line Lorlatinib for ALK-Positive Advanced NSCLC in the UK
Author(s)
Daniel Ladino, Masters1, Victoria Brodbin, Masters2, Carina Marie Behr, MSc, PhD3, Ian Gould, PhD4, Hannah Le, PharmD5.
1Lumanity, Dublin, Ireland, 2Pfizer, Tadworth, United Kingdom, 3Lumanity, Utrecht, Netherlands, 4Lumanity, Asheville, NC, USA, 5Pfizer, Fairfax, VA, USA.
1Lumanity, Dublin, Ireland, 2Pfizer, Tadworth, United Kingdom, 3Lumanity, Utrecht, Netherlands, 4Lumanity, Asheville, NC, USA, 5Pfizer, Fairfax, VA, USA.
OBJECTIVES: We evaluated the cost-effectiveness of first-line (1L) lorlatinib versus alectinib, the most used second-generation ALK tyrosine kinase inhibitor (TKI) in untreated patients with ALK-positive advanced non-small-cell lung cancer using a UK National Health Service perspective.
METHODS: On TA909, a pseudo-state-transition using three health states - progression-free (PF), progressed disease (PD) and death - was used to overcome the limitations caused by short overall survival follow-up and the use of subsequent treatments in CROWN not available in the UK, as flagged by the National Institute for Health and Care and Excellence (NICE) committee. While reviewing TA909, the NICE committee requested an update in the model structure that linked the survival benefits and costs of second-line (2L) lorlatinib treatment until progression after 1L second-generation ALK TKIs. A four-health state model comprising PF, PD1, PD2 and death was developed, and incorporated all previous preferred assumptions. The transition probabilities for lorlatinib followed by chemotherapy were derived using the CROWN trial and the chemotherapy arm from TA628 (2L lorlatinib submission); and for alectinib followed by lorlatinib using the CROWN trial and the progression-free survival (PFS) hazard ratio from the network meta-analysis, Study 1027 (2L lorlatinib Phase IV trial) and Study 1001 EXP3B:5 (lorlatinib single-arm Phase II trial).
RESULTS: Without considering commercial discounts, the incremental cost-effectiveness ratio (ICER) was £42,483 per quality adjusted life year (QALY) versus alectinib. However, the scenario analysis showed the ICER was sensitive to alternative and plausible post-progression survival assumptions in both treatment arms.
CONCLUSIONS: The decision problem of comparing 1L lorlatinib followed by chemotherapy versus 1L alectinib followed by lorlatinib or chemotherapy is subject to an inherent high uncertainty caused by low progression rates in the CROWN lorlatinib arm and lack of evidence of 2L lorlatinib post-progression survival. Therefore, decision-making should consider all potential and plausible scenarios for which lorlatinib is cost-effective.
METHODS: On TA909, a pseudo-state-transition using three health states - progression-free (PF), progressed disease (PD) and death - was used to overcome the limitations caused by short overall survival follow-up and the use of subsequent treatments in CROWN not available in the UK, as flagged by the National Institute for Health and Care and Excellence (NICE) committee. While reviewing TA909, the NICE committee requested an update in the model structure that linked the survival benefits and costs of second-line (2L) lorlatinib treatment until progression after 1L second-generation ALK TKIs. A four-health state model comprising PF, PD1, PD2 and death was developed, and incorporated all previous preferred assumptions. The transition probabilities for lorlatinib followed by chemotherapy were derived using the CROWN trial and the chemotherapy arm from TA628 (2L lorlatinib submission); and for alectinib followed by lorlatinib using the CROWN trial and the progression-free survival (PFS) hazard ratio from the network meta-analysis, Study 1027 (2L lorlatinib Phase IV trial) and Study 1001 EXP3B:5 (lorlatinib single-arm Phase II trial).
RESULTS: Without considering commercial discounts, the incremental cost-effectiveness ratio (ICER) was £42,483 per quality adjusted life year (QALY) versus alectinib. However, the scenario analysis showed the ICER was sensitive to alternative and plausible post-progression survival assumptions in both treatment arms.
CONCLUSIONS: The decision problem of comparing 1L lorlatinib followed by chemotherapy versus 1L alectinib followed by lorlatinib or chemotherapy is subject to an inherent high uncertainty caused by low progression rates in the CROWN lorlatinib arm and lack of evidence of 2L lorlatinib post-progression survival. Therefore, decision-making should consider all potential and plausible scenarios for which lorlatinib is cost-effective.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
EE251
Topic
Clinical Outcomes, Economic Evaluation, Health Technology Assessment
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Oncology