Trial reportTargeted oncology2020
Brain Penetration of Lorlatinib: Cumulative Incidences of CNS and Non-CNS Progression with Lorlatinib in Patients with Previously Treated ALK-Positive Non-Small-Cell Lung Cancer.
Trial report in Targeted oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01970865 (PHASE 1/2 STUDY OF PF-06463922), which is not on this map. Cited by 59 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 1/2 study of pf-06463922 (an alk/ros1 tyrosine kinase inhibitor) in patients with advanced non-small cell lung cancer harboring specific molecular alterations
Who cites it
59 citing papers in PubMed, 116 citations in OpenAlex.
- NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations.Cancer discovery · 2024Trial
- Phase II Study of Lorlatinib in Patients With Anaplastic Lymphoma Kinase-Positive Lung Cancer and CNS-Specific Relapse.JCO precision oncology · 2022Trial
- Rescuing a refractory Leiomyosarcoma: ALK-DCTN1 fusion as a gateway to long-term control with Ceritinib.Gynecologic oncology reports · 2026Article
- Antibody-drug conjugates in breast cancer brain and leptomeningeal metastases: mechanistic insights and therapeutic progress.Cancer metastasis reviews · 2026Review
- Pathophysiology and treatment of leptomeningeal metastases in lung cancer.Translational lung cancer research · 2026Review
- Role of signaling pathways in lung cancer development and advances in targeted therapies (Review).Oncology letters · 2025Review
- Lorlatinib and neurocognitive adverse events: characterization, risk factors, and the potentially mitigative role of social support.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Article
- Neurological adverse events of ROS1 inhibitors for non-small cell lung cancer: data from the FDA adverse event reporting system.Frontiers in neurology · 2025Article
- Case Report: Extended survival in KRAS-G12V NSCLC with leptomeningeal metastasis through integrated intrathecal chemotherapy and systemic therapies.Frontiers in pharmacology · 2025Article
- Cyp3a4-Mediated in vitro Metabolism and in vivo Disposition of Lorlatinib in Rats.Drug design, development and therapy · 2025Article
- ALK-positive histiocytosis with central nervous system involvement successfully treated with alectinib: a rare case report.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Leptomeningeal metastases from solid tumors: A Society for Neuro-Oncology and American Society of Clinical Oncology consensus review on clinical management and future directions.Neuro-oncology · 2024Review
- Preclinical evaluation of targeted therapies for central nervous system metastases.Disease models & mechanisms · 2024Review
- Neurocognitive Adverse Events Related to Lorlatinib in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.Cancers · 2024Article
- Efficacy and Safety of Dose-Escalated Alectinib in Patients With Metastatic ALK-Positive NSCLC and Central Nervous System Relapse on Standard-Dose Alectinib.JTO clinical and research reports · 2024Article
- Treatment sequencing after failure to alectinib in patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer.Cancer science · 2024Article
- Article
- ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Applications of cerebrospinal fluid circulating tumor cells and circulating tumor-derived DNA in diagnosis, prognosis, and personalized treatment of CNS metastases.Frontiers in oncology · 2024Review
- Enteral lorlatinib after immune hyperprogression as a treatment option for anaplastic lymphoma kinase‑positive non‑small cell lung cancer: A case report.Oncology letters · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLorlatinib is a potent, third-generation ALK/ROS1 tyrosine kinase inhibitor (TKI) designed to penetrate the blood-brain barrier.
objectiveWe report the cumulative incidence of central nervous system (CNS) and non-CNS progression with lorlatinib in patients with ALK-positive non-small-cell lung cancer (NSCLC) previously treated with ALK TKIs. PATIENTS AND
methodsIn an ongoing phase II study (NCT01970865), 198 patients with ALK-positive NSCLC with ≥ 1 prior ALK TKI were enrolled into expansion cohorts (EXP) based on treatment history. Patients received lorlatinib 100 mg once daily. Patients were analyzed for progressive disease, categorized as CNS or non-CNS progression, by independent central review. Cumulative incidence probabilities were calculated adopting a competing risks approach.
resultsFifty-nine patients received crizotinib as their only prior ALK TKI (EXP2-3A); cumulative incidence rates (CIRs) of CNS and non-CNS progression were both 22% at 12 months in patients with baseline CNS metastases (n = 37), and CIR of non-CNS progression at 12 months was higher versus that for CNS progression in patients without baseline CNS metastases [43% vs. 9% (n = 22)]. In patients who received ≥ 1 prior second-generation ALK TKI [EXP3B-5 (n = 139)], CIR of non-CNS progression at 12 months was higher versus that for CNS progression in patients both with and without baseline CNS metastases (35% vs. 23% (n = 94) and 55% vs. 12% (n = 45), respectively).
conclusionsLorlatinib showed substantial intracranial activity in patients with pretreated ALK-positive NSCLC, with or without baseline CNS metastases, whose disease progressed on crizotinib or second-generation ALK TKIs. CLINICALTRIALS. GOV IDENTIFIER: NCT01970865.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.