ArticleJTO clinical and research reports2024
ALKTERNATE: A Pilot Study Alternating Lorlatinib With Crizotinib in ALK-Positive NSCLC With Prior ALK Inhibitor Resistance.
Article in JTO clinical and research reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors.
Funding
Abstract
Introduction: ALK-positive lung cancers represent a molecularly diverse disease. With drug exposure, driving selection pressure, and resistance pathways, disease relapse will emerge. There is compelling rationale to investigate novel treatment strategies, informed by dynamic circulating tumor DNA (ctDNA) monitoring. Methods: The single-arm, pilot study ALKTERNATE investigated fixed alternating cycles of lorlatinib intercalated with crizotinib in individuals resistant to second-generation ALK inhibitors. Dynamic ctDNA explored the correlation with disease response and disease recurrence and defined disease resistance. The primary outcome was time-to-treatment failure, a composite of tolerability, feasibility, and efficacy. Secondary outcomes included standard survival measures, toxicity, pharmacokinetic analysis, and patient-reported outcomes. Tertiary outcomes were proteogenomic analyses of tissue and plasma. Results: A total of 15 individuals were enrolled; three encountered primary resistance to lorlatinib induction. There were 12 participants who received alternating therapy, and this approach revealed safety, feasibility, and effectiveness. Patient-reported outcomes were maintained or improved on therapy, and toxicity was consistent with previous reports. The pharmacokinetic measures were similar to the single-arm drug experience. Median time-to-treatment failure was 10 months; overall survival was 23 months. ctDNA profiles indicated inferior survival in those with preexistent TP53 mutations and those without clear or cleared ctDNA at trial induction. The study defined a vastly heterogeneous population with an abundance of ALK coexisting with non-ALK resistance variants. Conclusions: ALKTERNATE revealed feasibility with a novel alternating ALK inhibitor strategy in ALK-positive NSCLC. Results support progressing inquiry into this approach and propose a flexible design with drug(s) selected and alternating time frames, informed by real-time plasma profiling. Moving this concept to treatment naive may also optimize impact.
Indexed as
Identifiers
What Socratic 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 Socratic graph.