Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials

Doebele, Robert C.; Drilon, Alexander; Paz‐Ares, Luis; Siena, Salvatore; Shaw, Alice T.; Farago, Anna F.; Blakely, Collin M.; Seto, Takashi; Cho, Byoung Chul; Tosi, Diego; Besse, Benjamin; Chawla, Sant P.; Bazhenova, Lyudmila; Krauss, John C.; Chae, Young Kwang; Barve, Minal; Garrido‐Laguna, Ignacio; Liu, Stephen V.; Conkling, Paul; John, Thomas; Fakih, Marwan; Sigal, Darren; Loong, Herbert H.; Buchschacher, Gary L.; Garrido, Pilar; Nieva, Jorgé; Steuer, Conor E.; Overbeck, Tobias R.; Bowles, Daniel W.; Fox, Elizabeth; Riehl, Todd; Chow-Maneval, Edna; Simmons, Brian; Cui, Na; Johnson, Ann; Eng, Susan; Wilson, Timothy R.; Demetri, George D.

doi:10.1016/s1470-2045(19)30691-6

Cited by 1,285 publications

(1,066 citation statements)

References 29 publications

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“…In fact, the possibility of further implementing commercially available panels by spiking-in probes for genetic targets not included in the standard version of the assay allows to expand its detection capability. Indeed, beside PAX3, due to the recent therapeutic successes of NTRK fusions targeting drugs in solid tumors (7,8), we are in the process of customizing the AMP-FPS panel by including primers for NTRK1 and NTRK2 (currently only NTRK3 is covered by the AMP-FPS assay).…”

Section: Discussionmentioning

confidence: 99%

“…In the case of a positive result, beside the genes involved in the fusion, the inclusion in the pathology report of details about the fusion variant detected, including reading frame of the chimeric transcript (in frame/out of frame) and exons involved might be useful. This is of particular importance if the fusion protein is potentially actionable and the retention of specific domains in the chimeric protein is crucial for drug sensitivity, as in the case of NTRK fusions (7)(8)(9).…”

Section: Discussionmentioning

confidence: 99%

“…For example, certain rearrangements, such as those involving ALK in inflammatory myofibroblastic tumors or COL1A1-PDGFB in dermatofibrosarcoma protuberans, are predictive of the response to tyrosine kinase inhibitors (5,6). Moreover, the detection of NTRK fusions in a broad range of malignancies, including sarcomas, has gaining much attention due to the recent demonstration of therapeutic efficacy of a new class of tyrosine kinase inhibitors in NTRK rearranged tumors (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

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Next-Generation Sequencing Approaches for the Identification of Pathognomonic Fusion Transcripts in Sarcomas: The Experience of the Italian ACC Sarcoma Working Group

et al. 2020

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This work describes the setup of a shared platform among the laboratories of the Alleanza Contro il Cancro (ACC) Italian Research Network for the identification of fusion transcripts in sarcomas by using Next Generation Sequencing (NGS). Different NGS approaches, including anchored multiplex PCR and hybrid capture-based panels, were employed to profile a large set of sarcomas of different histotypes. The analysis confirmed the reliability of NGS RNA-based approaches in detecting sarcoma-specific rearrangements. Overall, the anchored multiplex PCR assay proved to be a fast and easy-to-analyze approach for routine diagnostics laboratories.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Next-Generation Sequencing Approaches for the Identification of Pathognomonic Fusion Transcripts in Sarcomas: The Experience of the Italian ACC Sarcoma Working Group

et al. 2020

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“…Larotrectinib and entrectinib are first-generation TRK inhibitors and have demonstrated rapid and durable responses and favorable safety profiles in patients with TRK fusion-positive cancers. Even if only few cases of CCA are included in a current basket trial evaluating Entrectinib, preliminary results are encouraging [68]. Therefore, Entrectinib is now under evaluation clinical trials in patients harboring ROS1 ALK fusions (NCT02568267) or TRKA (NCT02568267).…”

Section: Ros1 and Neurotrophic Tyrosine Kinase Receptor (Trka)mentioning

confidence: 99%

New and Emerging Systemic Therapeutic Options for Advanced Cholangiocarcinoma

Massironi

Pilla

Elvevi

et al. 2020

Cells

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Cholangiocarcinoma (CCA) represents a disease entity that comprises a heterogeneous group of biliary malignant neoplasms, with variable clinical presentation and severity. It may be classified according to its anatomical location and distinguished in intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA), each subtype implying distinct epidemiology, biology, prognosis, and strategy for clinical management. Its incidence has increased globally over the past few decades, and its mortality rate remains high due to both its biological aggressiveness and resistance to medical therapy. Surgery is the only potentially curative treatment and is the standard approach for resectable CCA; however, more than half of the patients have locally advanced or metastatic disease at presentation. For patients with unresectable CCA, the available systemic therapies are of limited effectiveness. However, the advances of the comprehension of the complex molecular landscape of CCA and its tumor microenvironment could provide new keys to better understand the pathogenesis, the mechanisms of resistance and ultimately to identify promising new therapeutic targets. Recently, clinical trials targeting isocitrate dehydrogenase (IDH)-1 mutations and fibroblast growth factor receptor (FGFR)-2 fusions, as well as immunotherapy showed promising results. All these new and emerging therapeutic options are herein discussed.

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“…Entrectinib is an oral tyrosine kinase inhibitor that inhibits ROS1, TRK, and ALK. At the European Society for Medical Oncology (ESMO) 2018 Congress, results from a pooled analysis of three studies in patients with NTRK fusions, STARTRK-2, STARTRK-1, and ALKA-372-001 studies, were presented [34]. The response rate among 54 patients with soft tissue sarcoma, non-small cell lung cancer, secretory carcinoma of the salivary gland, and other tumors was 57.4%.…”

Section: Trk Inhibitorsmentioning

confidence: 99%

Japan society of clinical oncology/Japanese society of medical oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese society of pediatric hematology/oncology

et al. 2020

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Background The development of novel antitumor agents and accompanying biomarkers has improved survival across several tumor types. Previously, we published provisional clinical opinion for the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair tumors. Recently, efficacy of tropomyosin receptor kinase inhibitors against neurotrophic receptor tyrosine kinase (NTRK) fusion gene-positive advanced solid tumors have been established as the second tumor-agnostic treatment, making it necessary to develop the guideline prioritized for these patients. Methods Clinical questions regarding medical care were formulated for patients with NTRK-positive advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by Japan Society of Clinical Oncology (JSCO) and Japanese Society of Medical Oncology (JSMO) voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and Japanese Society of Pediatric Hematology/Oncology, and the public comments among all Societies' members was done. Results The current guideline describes 3 clinical questions and 15 recommendations for whom, when, and how NTRK fusion should be tested, and what is recommended for patients with NTRK fusion-positive advanced solid tumors. Conclusion In the NTRK guideline, the committee proposed 15 recommendations for performing NTRK testing properly to select patients who are likely to benefit from tropomyosin receptor kinase inhibitors.

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Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials

Cited by 1,285 publications

References 29 publications

Next-Generation Sequencing Approaches for the Identification of Pathognomonic Fusion Transcripts in Sarcomas: The Experience of the Italian ACC Sarcoma Working Group

Next-Generation Sequencing Approaches for the Identification of Pathognomonic Fusion Transcripts in Sarcomas: The Experience of the Italian ACC Sarcoma Working Group

New and Emerging Systemic Therapeutic Options for Advanced Cholangiocarcinoma

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