ArticleJournal of the National Comprehensive Cancer Network : JNCCN2025
Efficacy and Safety of Continuing Next-Generation ALK TKIs With Chemotherapy for Advanced ALK-Positive NSCLC: A Multicenter Retrospective Study.
Article in Journal of the National Comprehensive Cancer Network : JNCCN, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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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.
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Who cites it
2 citing papers in PubMed.
- Review
- Clinical Activity of RET TKI Plus Chemotherapy After Progression on a RET TKI in aJTO clinical and research reports · 2026Article
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Authors and funding
26 authors.
Funding
Abstract
backgroundNext-generation ALK tyrosine kinase inhibitors (TKIs; eg, alectinib, brigatinib, ceritinib, ensartinib, lorlatinib) are established first-line therapies for patients with ALK fusion-positive (ALK+) advanced/metastatic non-small cell lung cancer (NSCLC). Chemotherapy-with platinum/pemetrexed (PT/Pem) as the preferred regimen-is considered standard next-line therapy. However, limited data exist on outcomes of continuing next-generation ALK TKIs with subsequent PT/Pem after progression on TKI monotherapy. PATIENTS AND
methodsThis multicentered, retrospective study included patients with ALK+ metastatic NSCLC who received PT/Pem alone or with alectinib or lorlatinib (PT/Pem/TKI) after progression on next-generation ALK TKIs. Endpoints included progression-free survival (PFS), overall survival (OS), 12-month cumulative incidence of intracranial progression, and treatment-related adverse events (trAEs).
resultsWe identified 156 patients, of whom 86 received PT/Pem and 70 received PT/Pem/TKI (alectinib: n=23; lorlatinib: n=47). Median PFS was numerically longer with PT/Pem/TKI versus PT/Pem (6.0 vs 3.5 months; hazard ratio [HR], 0.75; P=.11). In 78 patients treated with the current paradigm of first-line next-generation ALK TKIs, PT/Pem/TKI was associated with longer median PFS (6.6 vs 3.5 months; HR, 0.58; P=.042) and longer median OS (16.4 vs 11.4 months; HR, 0.55; P=.041) than PT/Pem alone. Among patients evaluable for intracranial outcomes (n=98), treatment with PT/Pem/TKI was associated with a significantly lower cumulative incidence of intracranial progression compared with PT/Pem alone (18.7% vs 34.0% at 12 months; HR, 0.33; P=.009). In the safety cohort (n=116), grade ≥3 trAEs occurred in 19 of 62 (30.6%) patients treated with PT/Pem, 5 of 18 (27.8%) patients treated with PT/Pem/alectinib, and 18 of 36 (50.0%) patients treated with PT/Pem/lorlatinib. There were no unanticipated safety signals in patients treated with PT/Pem plus alectinib or lorlatinib.
conclusionsAmong patients who received next-generation ALK TKIs as first-line therapy, continuation of next-generation ALK TKI with PT/Pem led to longer PFS and OS than PT/Pem alone, with no unanticipated toxicities. The modest efficacy of PT/Pem-based regimens overall underscores the need for more effective therapies for TKI-refractory ALK+ NSCLC.
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