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

García‐Foncillas, Jesús; Bokemeyer, Carsten; Italiano, Antoîne; Keating, Karen; Paracha, Noman; Fellous, Marc; Marian, Marisca; Fillbrunn, Mirko; Gao, Wei; Ayyagari, Rajeev; Lassen, Ulrik

doi:10.3390/cancers14071793

Cited by 12 publications

(5 citation statements)

References 25 publications

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“…Garcia-Foncillas et al ( 2022) reported that the MAIC demonstrated no statistically significant differences between larotrectinib and entrectinib for serious TRAEs or TRAEs leading to discontinuation. 86 As previously noted, firm conclusions should not be drawn from this MAIC regarding the comparative safety of entrectinib and larotrectinib due to important limitations with the analysis.…”

Section: Harmsmentioning

confidence: 89%

“…In the absence of direct or indirect evidence comparing entrectinib and larotrectinib in the submission, CADTH conducted a literature search to identify any relevant published indirect comparisons, and identified 1 MAIC that compared entrectinib and larotrectinib in adult patients with NTRK gene fusion-positive tumours. 86 Garcia-Foncillas et al ( 2022) reported that, compared with entrectinib, larotrectinib was associated with a statistically significantly greater duration of OS and DOR, with statistically significant differences for PFS or ORR. 86 However, due to major limitations associated with this study, firm conclusions for the efficacy and safety end points comparing entrectinib and larotrectinib are not recommended.…”

Section: Comparative Efficacymentioning

confidence: 99%

“…No limits were applied to the search. CADTH identified 1 MAIC that compared entrectinib and larotrectinib in adult patients with NTRK gene fusion-positive tumours 86.…”

mentioning

confidence: 99%

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Entrectinib (Rozlytrek)

CADTH¹

2023

cjht

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CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec. This review assesses Entrectinib (Rozlytrek) capsules, 100 mg and 200 mg, oral. Indication: For the treatment of adult patients who have unresectable, locally advanced or metastatic extracranial solid tumours (including brain metastases), that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation and no satisfactory treatment options.

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Section: Harmsmentioning

confidence: 89%

Section: Comparative Efficacymentioning

confidence: 99%

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Entrectinib (Rozlytrek)

CADTH¹

2023

cjht

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“…Two NTRK inhibitors, entrectinib and larotrectinib, received an agnostic approval from the FDA based on the results of the studies, which included a wide spectrum of NTRK-rearranged tumors [48,49]. Indirect comparisons of clinical data suggest that larotrectinib may be more efficacious than entrectinib in NTRK-driven malignancies [50][51][52]. Although NTRK1-3 rearrangements are frequently presented as an example of agnostic medicine, their actual utility is limited by some factors.…”

Section: Ntrk1-3 Rearrangementsmentioning

confidence: 99%

Agnostic Administration of Targeted Anticancer Drugs: Looking for a Balance between Hype and Caution

Aleksakhina,

Ivantsov,

Imyanitov

2024

IJMS

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Many tumors have well-defined vulnerabilities, thus potentially allowing highly specific and effective treatment. There is a spectrum of actionable genetic alterations which are shared across various tumor types and, therefore, can be targeted by a given drug irrespective of tumor histology. Several agnostic drug-target matches have already been approved for clinical use, e.g., immune therapy for tumors with microsatellite instability (MSI) and/or high tumor mutation burden (TMB), NTRK1-3 and RET inhibitors for cancers carrying rearrangements in these kinases, and dabrafenib plus trametinib for BRAF V600E mutated malignancies. Multiple lines of evidence suggest that this histology-independent approach is also reasonable for tumors carrying ALK and ROS1 translocations, biallelic BRCA1/2 inactivation and/or homologous recombination deficiency (HRD), strong HER2 amplification/overexpression coupled with the absence of other MAPK pathway-activating mutations, etc. On the other hand, some well-known targets are not agnostic: for example, PD-L1 expression is predictive for the efficacy of PD-L1/PD1 inhibitors only in some but not all cancer types. Unfortunately, the individual probability of finding a druggable target in a given tumor is relatively low, even with the use of comprehensive next-generation sequencing (NGS) assays. Nevertheless, the rapidly growing utilization of NGS will significantly increase the number of patients with highly unusual or exceptionally rare tumor-target combinations. Clinical trials may provide only a framework for treatment attitudes, while the decisions for individual patients usually require case-by-case consideration of the probability of deriving benefit from agnostic versus standard therapy, drug availability, associated costs, and other circumstances. The existing format of data dissemination may not be optimal for agnostic cancer medicine, as conventional scientific journals are understandably biased towards the publication of positive findings and usually discourage the submission of case reports. Despite all the limitations and concerns, histology-independent drug-target matching is certainly feasible and, therefore, will be increasingly utilized in the future.

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“…Clinical trials showed the significant advantage of larotrectinib administration in patients with TRK fusion-positive primary central nervous system (CNS) tumors. It demonstrated rapid and durable responses, a high disease control rate and a favorable safety profile [46,47].…”

Section: Larotrectinibmentioning

confidence: 99%

New therapeutic strategies based on molecularly targeted therapy in glioblastoma – a case report and review of the literature

Szklener

Anna

Kuryło

et al. 2022

Current Issues in Pharmacy and Medical Sciences

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Glioblastomas are the most common and most lethal forms of malignant primary brain tumor. We present a case report of a patient with III-grade glioma who achieved stable disease (SD) and clinical improvement after trametinib administration. We also report a review of the literature to Current Treatment Guidelines of Glioblastoma and new therapeutic strategies based on molecularly targeted therapy. Traditional treatments, including surgery, radiotherapy, and chemotherapy, have many limitations concerning the prognosis of patients with glioblastomas. Unfortunately, these tumors’recur after primary resection in the majority of cases. There is no standard therapy for recurrence of GBM. Targeted therapy offers a promising new treatment strategy. Regardless of those outstanding results much more can be done in the field of therapeutic options. Most urgent concerns include potent combining molecular targeted therapy with other types of treatments, selecting a group of patients for whom they turn out to be the most beneficial, and addressing adverse events of these molecules.

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

Cited by 12 publications

References 25 publications

Entrectinib (Rozlytrek)

Entrectinib (Rozlytrek)

Agnostic Administration of Targeted Anticancer Drugs: Looking for a Balance between Hype and Caution

New therapeutic strategies based on molecularly targeted therapy in glioblastoma – a case report and review of the literature

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