{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T11:00:34Z","timestamp":1790938834967,"version":"4.1.0"},"reference-count":38,"publisher":"Becaris Publishing Limited","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Comp. Eff. Res."],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>\n                    <jats:bold>Aim:<\/jats:bold>\n                    Lorlatinib and alectinib are next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) approved for the treatment of ALK-positive (ALK+) advanced\/metastatic non-small cell lung cancer (NSCLC) after demonstrating superior efficacy over crizotinib (first-generation ALK TKI) in the CROWN and ALEX trials, respectively. This analysis estimated the US population-level clinical impact of first-line (1L) lorlatinib versus alectinib treatment for ALK+ advanced\/metastatic NSCLC.\n                    <jats:bold>Materials &amp; methods:<\/jats:bold>\n                    We developed a decision-analytic model comparing lorlatinib versus alectinib use in 1L. We used a three-state partitioned survival model (pre-progression, post-progression and death) and tracked incidence of brain metastases (BMs). Lorlatinib-eligible population estimates were derived from published literature and market forecasts; treatment effectiveness for lorlatinib was derived from CROWN; alectinib comparative effectiveness was informed using a match-adjusted indirect comparison (CROWN vs ALEX). We assumed lorlatinib uptake of 38% in the base case; selected scenarios included different survival extrapolations, assuming 100% lorlatinib uptake and applying risk of BM post-discontinuation.\n                    <jats:bold>Results:<\/jats:bold>\n                    We estimated that 3096 patients in the US would be eligible for lorlatinib. Compared with 1L alectinib use only, our model projected that 1L lorlatinib treatment results in 1620\u20135170 and 1590\u20134880 more life-years and quality-adjusted life-years, respectively, over a 20-year time horizon across scenarios. Per-patient incidence of BM ranged from 0.14\u20130.18 and 0.21\u20130.40 for lorlatinib and alectinib, respectively, resulting in 68\u2013256 fewer BMs. Separately, for every 5\u201315 patients treated with 1L lorlatinib instead of 1L alectinib, one BM would be avoided.\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    This analysis projected that 1L lorlatinib treatment in the US could result in more LYs and quality-adjusted life-years and fewer BMs versus 1L alectinib in ALK+ advanced\/metastatic NSCLC.\n                  <\/jats:p>","DOI":"10.57264\/cer-2026-0096","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:24:17Z","timestamp":1788441857000},"source":"Crossref","is-referenced-by-count":0,"title":["US population-level model of clinical impact of lorlatinib treatment on ALK+ metastatic non-small cell lung cancer outcomes"],"prefix":"10.57264","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3468-8184","authenticated-orcid":false,"given":"Adam","family":"Kasle","sequence":"first","affiliation":[{"name":"Curta, Inc., Seattle, WA 98104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5269-2377","authenticated-orcid":false,"given":"Devin","family":"Abrahami","sequence":"additional","affiliation":[{"name":"HTA Value &amp; Evidence, Oncology, Pfizer Inc., New York, NY 10001, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Veenstra","sequence":"additional","affiliation":[{"name":"Curta, Inc., Seattle, WA 98104, USA"},{"name":"CHOICE Institute, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8723-2562","authenticated-orcid":false,"given":"Robert","family":"Morlock","sequence":"additional","affiliation":[{"name":"YourCareChoice, Ann Arbor, MI 48104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Pfizer Inc., New York, NY 10001, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Stansfield","sequence":"additional","affiliation":[{"name":"Pfizer Inc., New York, NY 10001, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8754-0565","authenticated-orcid":false,"given":"Raymond","family":"Mak","sequence":"additional","affiliation":[{"name":"Mass General Brigham, Boston, MA 02199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"36897","reference":[{"key":"e_1_3_8_2_2","unstructured":"American Cancer Society. 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EE69 Cost-utility analysis of lorlatinib for first-line treatment for ALK positive advanced non-small cell lung cancer in China. Value Health 26(12), S63 (2023).","journal-title":"Value Health"},{"issue":"4","key":"e_1_3_8_36_2","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s40258-023-00807-7","article-title":"Cost-effectiveness of lorlatinib in first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer in Sweden","volume":"21","author":"Naik J","year":"2023","unstructured":"Naik J, Beavers N, Nilsson FOL, Iadeluca L, Lowry C. Cost-effectiveness of lorlatinib in first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer in Sweden. Appl. Health Econ. Health Pol. 21(4), 661\u2013672 (2023).","journal-title":"Appl. Health Econ. Health Pol."},{"key":"e_1_3_8_37_2","doi-asserted-by":"crossref","first-page":"659","DOI":"10.2147\/CEOR.S415711","article-title":"Cost-effectiveness of lorlatinib for the treatment of adult patients with anaplastic lymphoma kinase positive advanced non-small cell lung cancer in Spain","volume":"15","author":"Presa M","year":"2023","unstructured":"Presa M, Vicente D, Calles A Cost-effectiveness of lorlatinib for the treatment of adult patients with anaplastic lymphoma kinase positive advanced non-small cell lung cancer in Spain. Clinicoecon. Outcomes Res. 15, 659\u2013671 (2023).","journal-title":"Clinicoecon. Outcomes Res."},{"key":"e_1_3_8_38_2","doi-asserted-by":"crossref","first-page":"985834","DOI":"10.3389\/fpubh.2022.985834","article-title":"Cost-effectiveness of ensartinib, crizotinib, ceritinib, alectinib, brigatinib and lorlatinib in patients with anaplastic lymphoma kinase-positive non-small cell lung cancer in China","volume":"10","author":"Luo X","year":"2022","unstructured":"Luo X, Zhou Z, Zeng X, Peng L, Liu Q. Cost-effectiveness of ensartinib, crizotinib, ceritinib, alectinib, brigatinib and lorlatinib in patients with anaplastic lymphoma kinase-positive non-small cell lung cancer in China. Front. Public Health 10, 985834 (2022).","journal-title":"Front. 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Insights Oncol."}],"container-title":["Journal of Comparative Effectiveness Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/becarispublishing.com\/doi\/pdf\/10.57264\/cer-2026-0096","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:42:56Z","timestamp":1790937776000},"score":1,"resource":{"primary":{"URL":"https:\/\/becarispublishing.com\/doi\/10.57264\/cer-2026-0096"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":38,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.57264\/cer-2026-0096"],"URL":"https:\/\/doi.org\/10.57264\/cer-2026-0096","relation":{},"ISSN":["2042-6305","2042-6313"],"issn-type":[{"value":"2042-6305","type":"print"},{"value":"2042-6313","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"article-number":"e260096"}}