Ahn, Myung-JuMyung-JuAhnDelmonte, AngeloAngeloDelmonteGhosh, SharmisthaSharmisthaGhoshHochmair, MaximilianMaximilianHochmairYang, Tsung-YingTsung-YingYangCHIH-HSIN YANGHan, Ji-YounJi-YounHanHansen, Karin HolmskovKarin HolmskovHansenWu, YanyuYanyuWuWan, YinYinWanLin, Huamao MarkHuamao MarkLinKretz, JulianJulianKretzHupf, BradleyBradleyHupfKurec, Ahmet MelihAhmet MelihKurecChurchill, Eric NEric NChurchillFram, Robert JRobert JFramCabasag, Citadel JungcoCitadel JungcoCabasagGoriya, VishalVishalGoriyaZhao, YuzheYuzheZhaoCampelo, Maria Rosario GarcíaMaria Rosario GarcíaCampelo2026-01-092026-01-092025-12https://scholars.lib.ntu.edu.tw/handle/123456789/735210This retrospective, chart-review study evaluated real-world outcomes post-frontline brigatinib in ALTA-1L.Patients from ALTA-1L were followed after brigatinib discontinuation. Outcomes evaluated for second-line (2L) treatment included real-world overall response rate (rwORR), time to treatment discontinuation (rwTTD), and progression-free survival (rwPFS).Forty of 48 patients received subsequent systemic anticancer therapies; 30 received 2L ALK tyrosine kinase inhibitors (TKIs), mostly lorlatinib (n = 16) or alectinib (n = 8), and 11 received 2L non-ALK TKI therapy (one with alectinib). rwORR was 33% with 2L ALK TKIs and 0% with 2L non-ALK TKI therapy. Median (95% confidence interval [CI]) 2L rwTTD was 34.7 months (4.6-not reached [NR]) for ALK TKIs (lorlatinib, 37.2 months [6.0-NR]; alectinib, NR [1.1-NR]; crizotinib, 2.8 months [2.0-NR]) and 4.4 months (1.4-6.0) for 2L non-ALK TKI therapy. Median (95% CI) 2L rwPFS was 16.1 months (4.4-NR) with ALK TKIs (lorlatinib, 25.6 months [3.8-NR]; alectinib, 16.1 months [1.1-NR]; crizotinib, 2.4 months [2.0-NR]) and 6.1 months (1.7-NR) with 2L non-ALK TKI therapy.Following brigatinib discontinuation, most patients initiated a second ALK TKI. Patients treated with 2L second- or third-generation ALK TKIs post-brigatinib experienced prolonged clinical benefit.clinicaltrials.gov identifier: NCT02737501.The ALTA-1L study looked at patients with + non-small cell lung cancer (NSCLC) that had spread beyond the lungs (metastatic) who had not yet been treated. The results showed that patients had a better chance of living longer or living without their disease becoming worse when they were treated with brigatinib, an ALK tyrosine kinase inhibitor (TKI), versus crizotinib, another ALK TKI. There is not much information on the best treatment for patients after brigatinib therapy. This real-world study evaluated additional treatments and outcomes in patients from the ALTA-1L study after they stopped treatment with brigatinib as first-line treatment of metastatic NSCLC.Among 40 patients who stopped brigatinib treatment in ALTA-1L and received additional treatment, 30 received another ALK TKI, most commonly lorlatinib and alectinib, and/or non–ALK TKI therapy. Patients who received a subsequent second- or third-generation ALK TKI had better outcomes than patients who received first-generation ALK TKI or non–ALK TKI therapy. Adverse events of special interest (AESIs) rates were lower with subsequent non–ALK TKI therapy than with subsequent ALK TKI therapy; AESIs occurred most frequently if the second ALK TKI was lorlatinib, but most AESIs were nonserious.Patients treated with brigatinib who stopped treatment and then received another second- or third-generation ALK TKI, such as lorlatinib, had longer-lasting clinical benefits than those who received subsequent first-generation ALK TKI or non–ALK TKI therapy.enLorlatinibalectinibcrizotinibnon–small cell lung carcinomatreatment sequencing[SDGs]SDG3journal article10.1080/14796694.2025.259252741410381