Larotrectinib efficacy and safety in TRK fusion cancer: An expanded clinical dataset showing consistency in an age and tumor agnostic approach

Tan, Daniel Shao-Weng; Lassen, Ulrik; Albert, Catherine M.; Kummar, S.; Tilburg, Cornelis van; Dubois, S.G.; Geoerger, Birgit; Mascarenhas, Leo; Federman, Noah; Basu-Mallick, Atrayee; Doz, François; Berlin, J.; Oh, Do Youn; Bielack, Stefan; McDermott, R.L.; Cruickshank, Scott; Ku, N.C.; Cox, Michael C.; Drilon, A.; Hong, D.S.

doi:10.1093/annonc/mdy430

Cited by 7 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Larotrectinib is a highly selective inhibitor of tropomyosin receptor kinase (TRK) A, B, and C ( Table 1 ), and is approved by FDA and EMA for the treatment of all solid cancers that harbor NTRK fusions, both in adult and in pediatric patients. The results of two phase 1 trials and of one phase 2 trial were all together reported in a primary analysis [ 95 ] and then in an additional paper with 67 supplemental patients [ 96 ]. Supplemental analysis included 109 patients with solid tumors, comprising 19% of TC.…”

Section: Current Available Systemic Therapies For the Treatment Ofmentioning

confidence: 99%

Thyroid Cancers: From Surgery to Current and Future Systemic Therapies through Their Molecular Identities

Lorusso

Cappagli

Valerio

et al. 2021

IJMS

View full text Add to dashboard Cite

Differentiated thyroid cancers (DTC) are commonly and successfully treated with total thyroidectomy plus/minus radioiodine therapy (RAI). Medullary thyroid cancer (MTC) is only treated with surgery but only intrathyroidal tumors are cured. The worst prognosis is for anaplastic (ATC) and poorly differentiated thyroid cancer (PDTC). Whenever a local or metastatic advanced disease is present, other treatments are required, varying from local to systemic therapies. In the last decade, the efficacy of the targeted therapies and, in particular, tyrosine kinase inhibitors (TKIs) has been demonstrated. They can prolong the disease progression-free survival and represent the most important therapeutic option for the treatment of advanced and progressive thyroid cancer. Currently, lenvatinib and sorafenib are the approved drugs for the treatment of RAI-refractory DTC and PDTC while advanced MTC can be treated with either cabozantinib or vandetanib. Dabrafenib plus trametinib is the only approved treatment by FDA for BRAFV600E mutated ATC. A new generation of TKIs, specifically for single altered oncogenes, is under evaluation in phase 2 and 3 clinical trials. The aim of this review was to provide an overview of the current and future treatments of thyroid cancer with regards to the advanced and progressive cases that require systemic therapies that are becoming more and more targeted on the molecular identity of the tumor.

show abstract

Section: Current Available Systemic Therapies For the Treatment Ofmentioning

confidence: 99%

Thyroid Cancers: From Surgery to Current and Future Systemic Therapies through Their Molecular Identities

Lorusso

Cappagli

Valerio

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Remarkably, 84% of the responding patients and 73% of all patients remained on larotrectinib or underwent surgery with curative intent. Strikingly, larotrectinib demonstrated clinical benefit regardless of tumour type, NTRK gene, fusion partner or age of the patient (Tan et al ., ). Both of these approvals inaugurate a new area, with multiple new agents, such as RET inhibitors, following this new path (Garber, ; Subbiah et al ., ).…”

Section: Precision Medicine Trials For Cancermentioning

confidence: 99%

New clinical trial designs in the era of precision medicine

et al. 2019

View full text Add to dashboard Cite

Cancer treatment has made significant strides towards the promise of personalized medicine. Recent scientific advances have shown that there are numerous genetic deregulations that are common in multiple cancer types, raising the possibility of developing drugs targeting those deregulations irrespective of the tumour type. Precision Cancer Medicine (PCM) was born out of accumulated evidence matching targeted agents with these tumour molecular deregulations. At the same time, the therapeutic armamentarium is rapidly increasing and the number of new drugs (including immune‐oncology agents) entering drug development continues to rise. These factors, added to strong collaboration with regulatory agencies, which have approved novel agents based on data obtained from phase 1/2 trials, have led to unprecedented evolution in the design of early‐stage clinical trials. Currently, we have seen rapid phase 1 dose‐escalation trials followed by remarkably large expansion cohorts, and are witnessing the emergence of new trials, such as adaptive studies with basket and umbrella designs aimed at optimizing the biomarker–drug co‐development process. Alongside the growing complexity of these clinical trials, new frameworks for stronger and faster collaboration between all stakeholders in drug development, including academic institutions and frameworks, clinicians, pharma companies and regulatory agencies, have been established. In this review article, we describe the main challenges and opportunities that these new trial designs may provide for a more efficient drug development process, which may ultimately help ensure that PCM becomes a reality for patients.

show abstract

“…All cases were evaluated by sequencing (NGS) or FISH. 60 , 61 For the cut-off period for data of July 2018, the ORR was 81% (95% CI 72–88) with complete and partial responses in 17% and 63% of patients, respectively. This was for an updated analysis of 109 pediatric and adult patients evaluable after a median monitoring of 17.6 months.…”

Section: Larotrectinib As An Example Of Precision Oncology Practicementioning

confidence: 99%

“…In the combination of primary data (55 patients), the median was not reached for DoR. 61 Figure 8 summarizes the response indexes in the study sequence of larotrectinib versus the threshold for other conventional therapies before the advent of the tyrosine kinase inhibitor. In the same way, Figure 9 discriminates individual response distribution in the integrated set of patients (diverse neoplasias, n = 109).…”

Section: Larotrectinib As An Example Of Precision Oncology Practicementioning

confidence: 99%

See 1 more Smart Citation

Precision medicine and its implementation in patients with NTRK fusion genes: perspective from developing countries

Zorrilla

Arrieta

Ruíz-Patiño

et al. 2020

Ther Adv Respir Dis

View full text Add to dashboard Cite

Precision oncology is the field that places emphasis on the diagnosis and treatment of tumors that harbor specific genomic alterations susceptible to inhibition or modulation. Although most alterations are only present in a minority of patients, a substantial effect on survival can be observed in this subgroup. Mass genome sequencing has led to the identification of a specific driver in the translocations of the tropomyosin receptor kinase family (NTRK) in a subset of rare tumors both in children and in adults, and to the development and investigation of Larotrectinib. This medication was granted approval by the US Food and Drug Administration for NTRK-positive tumors, regardless of histology or age group, as such, larotrectinib was the first in its kind to be approved under the premise that molecular pattern is more important than histology in terms of therapeutic approach. It yielded significant results in disease control with good tolerability across a wide range of diseases including rare pediatric tumors, salivary gland tumors, gliomas, soft-tissue sarcomas, and thyroid carcinomas. In addition, and by taking different approaches in clinical trial design and conducting allocation based on biomarkers, the effects of target therapies can be isolated and quantified. Moreover, and considering developing nations and resource-limited settings, precision oncology could offer a tool to reduce cancer-related disability and hospital costs. In addition, developing nations also present patients with rare tumors that lack a chance of treatment, outside of clinical trials. This, in turn, offers the possibility for international collaboration, and contributes to employment, education, and health service provisions. The reviews of this paper are available via the supplemental material section.

show abstract

Larotrectinib efficacy and safety in TRK fusion cancer: An expanded clinical dataset showing consistency in an age and tumor agnostic approach

Cited by 7 publications

References 0 publications

Thyroid Cancers: From Surgery to Current and Future Systemic Therapies through Their Molecular Identities

Thyroid Cancers: From Surgery to Current and Future Systemic Therapies through Their Molecular Identities

New clinical trial designs in the era of precision medicine

Precision medicine and its implementation in patients with NTRK fusion genes: perspective from developing countries

Contact Info

Product

Resources

About