Transforming approaches to treating TRK fusion cancer: historical comparison of larotrectinib and histology-specific therapies

Pollack, Megan; Keating, Karen; Wissinger, Erika; Jackson, Louis; Sarnes, Evelyn; Cuffel, Brian J.

doi:10.1080/03007995.2020.1847057

Cited by 6 publications

(2 citation statements)

References 137 publications

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“…Pharmaceutical research will at first be helped by the new precise molecular disease definitions and diagnostics for patient inclusion, which de-risk drug discovery considerably 71,72 . The earliest example and application of a mechanistic redefinition of disease and mechanistic drug approval are pembrolizumab (Keytruda ® ) and larotrectinib (Vitrakvi ® ), two cancer drugs based on gene variants rather than an organbased or histological tumour definition 73,74 .…”

Section: Implications For Clinical Practice Research and Drug Discoverymentioning

confidence: 99%

Why the way we define diseases prevents innovation and precision medicine

Mamdouh

Anastasi

Hassan

et al. 2023

Preprint

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Noncommunicable diseases (NCDs) have become globally abundant, yet the therapeutics we use for them are imprecise. In parallel, identifying new treatments has become more costly than ever due to the ever-aggravating efficacy crisis drug discovery faces. What unites these failures is our ontological classification of diseases, primarily based on descriptive terms. To achieve precision diagnosis and precision therapy in clinical practice, NCDs need to be redefined and subdivided based on their causal molecular mechanisms. However, the inconsistency and incompatibility of the current disease classification systems hinder data integration and analysis towards the characterization of such mechanisms. Here, we explain flaws in the current disease definitions and the dispersion among existing ontologies with the aim of establishing a mechanism-based classification of diseases hence, precision medicine.

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Section: Implications For Clinical Practice Research and Drug Discoverymentioning

confidence: 99%

Why the way we define diseases prevents innovation and precision medicine

Mamdouh

Anastasi

Hassan

et al. 2023

Preprint

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“…Previously, treatment options for TRK cancers were limited to chemotherapy, biologic therapy, or immunotherapy [ 7 ]. The development of targeted agents has dramatically improved the treatment landscape for patients harboring NTRK gene fusions [ 3 , 8 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Indirect Treatment Comparison of Larotrectinib versus Entrectinib in Treating Patients with TRK Gene Fusion Cancers

García‐Foncillas

Bokemeyer

Italiano

et al. 2022

Cancers

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Information regarding the comparative efficacy of first-generation receptor tyrosine kinase inhibitors is limited. This matching-adjusted indirect comparison (MAIC) evaluated differences in efficacy and safety across larotrectinib and entrectinib trials. Data from clinical trials for larotrectinib (LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431)) and entrectinib (ALKA-372-001 (EudraCT 2012-000148-88), STARTRK-1 (NCT02097810), and STARTRK-2 (NCT02568267)) were used. Adults (≥18 years) across trials were matched on available baseline characteristics. Outcomes evaluated included overall response rate (ORR), complete response (CR) rate, duration of response (DoR), overall survival (OS), progression-free survival (PFS), any serious treatment-related adverse events of grade ≥ 3 (TRAEs), and TRAEs leading to treatment discontinuation. The MAIC included 74 patients from entrectinib trials and 117 and 147 patients for the larotrectinib efficacy and safety populations, respectively. Post-matching, larotrectinib was associated with a significantly longer median duration of OS than entrectinib (p < 0.05) and a numerically longer median PFS (p = 0.07). ORR was similar for both agents (p = 0.63). The CR rate was higher (p < 0.05) and the DoR was longer for larotrectinib (p < 0.05). Safety outcomes were comparable and low for both treatments. Results were consistent in sensitivity analyses. These findings suggest favorable efficacy for larotrectinib and comparable safety profiles versus entrectinib in treating tropomyosin receptor kinase fusion cancer.

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Definition of “Tissue-Based Biomarker,” its Place in Medicine, and Molecular Pathology

Sağol

Sarıoğlu

2022

Biomarkers in Carcinoma of Unknown Primary

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Transforming approaches to treating TRK fusion cancer: historical comparison of larotrectinib and histology-specific therapies

Abstract: Data availability statement: Review article; no data/results provided in this publication.

Cited by 6 publications

References 137 publications

Why the way we define diseases prevents innovation and precision medicine

Why the way we define diseases prevents innovation and precision medicine

Indirect Treatment Comparison of Larotrectinib versus Entrectinib in Treating Patients with TRK Gene Fusion Cancers

Definition of “Tissue-Based Biomarker,” its Place in Medicine, and Molecular Pathology

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