Article
Oncology
Francois Doz, Cornelis M. van Tilburg, Birgit Geoerger, Martin Hojgaard, Ingrid Ora, Valentina Boni, Michael Capra, Julia Chisholm, Hyun Cheol Chung, Steven G. DuBois, Soledad Gallego-Melcon, Nicolas U. Gerber, Hiroaki Goto, Juneko E. Grilley-Olson, Jordan R. Hansford, David S. Hong, Antoine Italiano, Hyoung Jin Kang, Karsten Nysom, Anne Thorwarth, Joanna Stefanowicz, Makoto Tahara, David S. Ziegler, Igor T. Gavrilovic, Ricarda Norenberg, Laura Dima, Esther De la Cuesta, Theodore W. Laetsch, Alexander Drilon, Sebastien Perreault
Summary: In patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated rapid and durable responses, high disease control rate, and a favorable safety profile.
Article
Endocrinology & Metabolism
Steven G. Waguespack, Alexander Drilon, Jessica J. Lin, Marcia S. Brose, Ray McDermott, Mohammed Almubarak, Jessica Bauman, Michela Casanova, Anuradha Krishnamurthy, Shivaani Kummar, Serge Leyvraz, Do-Youn Oh, Keunchil Park, Davendra Sohal, Eric Sherman, Ricarda Norenberg, Josh D. Silvertown, Nicoletta Brega, David S. Hong, Maria E. Cabanillas
Summary: This study evaluated the efficacy and safety of Larotrectinib in patients with TRK fusion-positive thyroid carcinoma. The results showed that Larotrectinib demonstrated rapid and durable disease control and a favorable safety profile in these patients, making it a potential treatment option for advanced thyroid carcinoma.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Oncology
James C. H. Yang, Marcia S. Brose, Gilberto Castro, Edward S. Kim, Ulrik N. Lassen, Serge Leyvraz, Alberto Pappo, Fernando Lopez-Rios, John A. Reeves, Marc Fellous, Frederique Penault-Llorca, Erin R. Rudzinski, Ghazaleh Tabatabai, Gilles Vassal, Alexander Drilon, Jonathan Trent
Summary: This article introduces the background and research objectives of Larotrectinib as a drug for the treatment of TRK fusion solid tumors. The study will observe the safety and effectiveness of Larotrectinib in different populations, including adult and pediatric patients, and describe the treatment patterns of Larotrectinib in real-world practice.
Article
Oncology
Xiuning Le, Christina Baik, Jessica Bauman, Jill Gilbert, Marcia S. Brose, Juneko E. Grilley-Olson, Tejas Patil, Ray McDermott, Luis E. Raez, Jennifer M. Johnson, Lin Shen, Makoto Tahara, Alan L. Ho, Ricarda Norenberg, Laura Dima, Nicoletta Brega, Alexander Drilon, David S. Hong
Summary: This article investigates the efficacy and safety of larotrectinib in patients with TRK fusion-positive salivary gland cancers. The results demonstrate that larotrectinib has robust and durable efficacy in treating different histologies of salivary gland tumors, with minimal side effects. These findings emphasize the importance of testing salivary gland cancer for NTRK gene fusions.
Article
Oncology
Shivaani Kummar, Lin Shen, David S. Hong, Ray McDermott, Vicki L. Keedy, Michela Casanova, George D. Demetri, Afshin Dowlati, Soledad Gallego Melcon, Ulrik N. Lassen, Serge Leyvraz, Tianshu Liu, Victor Moreno, Jyoti Patel, Tejas Patil, Atrayee Basu Mallick, Nuno Sousa, Makoto Tahara, David S. Ziegler, Ricarda Norenberg, Pierre Arvis, Nicoletta Brega, Alexander Drilon, Daniel S. W. Tan
Summary: Larotrectinib showed good efficacy and safety in adult patients with TRK fusion sarcomas, with extended survival benefit and durable objective response rate.
Article
Oncology
Jesus Garcia-Foncillas, Carsten Bokemeyer, Antoine Italiano, Karen Keating, Noman Paracha, Marc Fellous, Marisca Marian, Mirko Fillbrunn, Wei Gao, Rajeev Ayyagari, Ulrik Lassen
Summary: This study compared the efficacy and safety of larotrectinib and entrectinib in the treatment of TRK fusion-positive cancer. The results showed that larotrectinib had a higher overall survival, longer duration of response, and higher complete response rates compared to entrectinib, with similar overall response and safety rates.
Review
Pharmacology & Pharmacy
Nathan D. Seligson, Todd C. Knepper, Susanne Ragg, Christine M. Walko
Summary: Targeted therapies have revolutionized cancer treatment, with recent biomarker-driven, tissue-agnostic clinical trials marking a significant shift towards precision medicine. However, only a few tissue-agnostic indications have been approved by the FDA so far, highlighting challenges such as complex cancer biology, clinical trial design, and resistance mechanisms that future therapies targeting tissue-agnostic indications will need to overcome.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Meteorology & Atmospheric Sciences
Chunlin Jin, Yong Xue, Xingxing Jiang, Liang Zhao, Tao Yuan, Yuxin Sun, Shuhui Wu, Xiangkai Wang
Summary: This paper re-evaluates the uncertainty of global XCO2 pixels using satellite observations and TCCON data, and improves the spatial and temporal resolution of the satellite data through software processing to reduce errors. Finally, a high-precision global XCO2 dataset is generated.
ATMOSPHERIC RESEARCH
(2022)
Article
Genetics & Heredity
Joshua D. Silvertown, Connie Lisle, Laura Semenuk, Colleen Knapp, Jillann Jaynes, Doreen Berg, Nabodita Kaul, Josianne Lachapelle, Leslie Richardson, Marsha Speevak, Haya Sarras, David M. Berman, Ronald Carter, Harriet Feilotter, Timothy Feltis
Summary: This study investigated the prevalence of NTRK fusions in Canadian patients and provided guidance for NTRK testing paradigms. The results showed that NTRK fusions were present in 0.71% of patients, and clinically actionable incidental findings were also detected. The testing algorithm played an important role in screening patient samples.
MOLECULAR DIAGNOSIS & THERAPY
(2023)
Article
Oncology
D. Gwyn Bebb, Shantanu Banerji, Normand Blais, Patrice Desmeules, Sharlene Gill, Andrea Grin, Harriet Feilotter, Aaron R. Hansen, Martin Hyrcza, Monika Krzyzanowska, Barbara Melosky, Jonathan Noujaim, Bibiana Purgina, Dean Ruether, Christine E. Simmons, Denis Soulieres, Emina Emilia Torlakovic, Ming-Sound Tsao
Summary: TRK inhibitors larotrectinib and entrectinib have been recently approved in Canada for treating solid tumors with NTRK gene fusions. These gene fusions are found at low frequency in most tumor types, and at higher frequency in rare tumors. The inhibitors have shown impressive efficacy and tolerability in clinical trials. Canada has developed a consensus on testing and treatment for NTRK gene fusions.
Editorial Material
Oncology
Erin R. Rudzinski, Alexander Drilon, Amy Moore, Susan Spinosa, Michaela Willi, Theodore W. Laetsch
Summary: This summary highlights a study on the different tests used to detect TRK fusion cancer in participants of clinical trials for larotrectinib. The study provides guidance for healthcare professionals and insights on the importance of testing different cancer types.
Review
Chemistry, Medicinal
Sun-Young Han
Summary: Recently approved Trk inhibitors, larotrectinib and entrectinib, have shown promising results for Trk fusion-positive cancer patients, using a tissue-agnostic development approach to expedite the drug development process. The on-target effects of Trk inhibitors on the central nervous system pose challenges, but a next generation sequencing-based companion diagnostic has been approved for detecting various types of Trk fusions. Through the adoption of tissue-agnostic approach, the development of Trk inhibitors has been accelerated.
Article
Health Care Sciences & Services
Josh J. Carlson, Antoine Italiano, Marcia S. Brose, Noah Federman, Ulrik Lassen, Shivaani Kummar, Sean D. Sullivan
Summary: Larotrectinib and entrectinib are both TRK inhibitors indicated for cancers with NTRK gene fusions, but there is a lack of direct comparative studies between the two. Historical and intrapatient comparisons suggest that TRK inhibitors may be more effective than existing treatments, with limited data indicating a potential advantage for larotrectinib in terms of clinical response and survival.
AMERICAN JOURNAL OF MANAGED CARE
(2022)
Article
Oncology
Lily Deland, Simon Keane, Thomas Olsson Bontell, Helene Sjogren, Henrik Fagman, Ingrid ora, Esther de la Cuesta, Magnus Tisell, Jonas A. Nilsson, Katarina Ejeskar, Magnus Sabel, Frida Abel
Summary: An 11-year-old girl with inoperable tumor in the optic chiasm/hypothalamus, classified as BRAF-negative pilocytic astrocytoma, was found to have a rare GKAP1-NTRK2 fusion gene through comprehensive molecular screening. Treatment with TRK-inhibitor resulted in tumor growth arrest, stable condition, and significant improvement in quality of life. This case highlights the importance of molecular screening for precision therapy in pediatric low-grade gliomas.
CANCER BIOLOGY & THERAPY
(2021)
Review
Oncology
Theodore W. Laetsch, David S. Hong
Summary: Chromosomal rearrangements of NTRK1-3 resulting in gene fusions have been validated as oncogenic drivers in human cancers. Two TRK inhibitors have been approved for treating patients with solid tumors harboring NTRK gene fusions, highlighting the importance of detecting these fusions and understanding the pharmacological properties of TRK inhibitors.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
J. J. Lin, A. Muzikansky, E. Kennedy, H. Kuberski, L. L. Stober, A. C. Wanat, C. G. Azzoli, I Lennes, L. Sequist, I Dagogo-Jack, A. T. Shaw, J. F. Gainor
Summary: This study aimed to evaluate the safety and efficacy of combining alectinib with bevacizumab in patients with advanced ALK-rearranged non-small-cell lung cancer, and the results showed that this combination therapy had good tolerability and efficacy.
Meeting Abstract
Oncology
V. Moreno, J. J. Lin, D. S. W. Tan, U. N. Lassen, S. Leyvraz, Y. Liu, J. Patel, L. Rosen, B. Solomon, M. Rudolph, R. Norenberg, A. Schulz, M. Fellous, N. Brega, L. Shen, S. Kummar, A. Drilon
ANNALS OF ONCOLOGY
(2022)
Correction
Oncology
George D. Demetri, Filippo De Braud, Alexander Drilon, Salvatore Siena, Manish R. Patel, Byoung Chul Cho, Stephen Liu, Myung-Ju Ahn, Chao-Hua Chiu, Jessica J. Lin, Koichi Goto, Jeeyun Lee, Lyudmila Bazhenova, Thomas John, Marwan Fakih, Sant P. Chawla, Rafal Dziadziuszko, Takashi Seto, Sebastian Heinzmann, Bethany Pitcher, David Chen, Timothy R. Wilson, Christian Rolfo
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Jessica J. J. Lin, Justin F. F. Gainor
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Ibiayi Dagogo-Jack, Antonello Abbattista, John F. Murphy, Stan Krulewicz, Andrew Do, Jennifer Peterson, Jessica J. Lin, Justin F. Gainor, Rossella Messina, Elizabeth A. Krueger, Holger Thurm, Beow Y. Yeap
Summary: This study analyzed the safety profile of lorlatinib and identified several factors associated with developing neurocognitive adverse events (NAEs), including brain metastases, brain radiation, psychiatric illness, and the use of neurotropic medications.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Letter
Oncology
Or Kalchiem-Dekel, Christine M. Bestvina, Justin F. Gainor, Alexander Drilon, Jessica J. Lin
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Oncology
Alexander Drilon, Joshua C. Horan, Anupong Tangpeerachaikul, Benjamin Besse, Sai-Hong Ignatius Ou, Shirish M. Gadgeel, D. Ross Camidge, Anthonie J. van der Wekken, Linh Nguyen-Phuong, Adam Acker, Clare Keddy, Katelyn S. Nicholson, Satoshi Yoda, Scot Mente, Yuting Sun, John R. Soglia, Nancy E. Kohl, James R. Porter, Matthew D. Shair, Viola Zhu, Monika A. Davare, Aaron N. Hata, Henry E. Pelish, Jessica J. Lin
Editorial Material
Critical Care Medicine
Jessica J. Lin, Justin F. Gainor
LANCET RESPIRATORY MEDICINE
(2023)
Article
Oncology
Joao V. Alessi, Arielle Elkrief, Biagio Ricciuti, Xinan Wang, Alessio Cortellini, Victor R. Vaz, Giuseppe Lamberti, Rosa L. Frias, Deepti Venkatraman, Claudia A. M. Fulgenzi, Federica Pecci, Gonzalo Recondo, Alessandro Di Federico, Adriana Barrichello, Hyesun Park, Mizuki Nishino, Grace M. Hambelton, Jacklynn V. Egger, Marc Ladanyi, Subba Digumarthy, Bruce E. Johnson, David C. Christiani, Xihong Lin, Justin F. Gainor, Jessica J. Lin, David J. Pinato, Adam J. Schoenfeld, Mark M. Awad
Summary: The efficacy of chemoimmunotherapy (CIT) in advanced NSCLC is associated with factors such as performance status, neutrophil-to-lymphocyte ratio, PD-L1 expression, and tumor mutational burden.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Review
Oncology
Jaime L. Schneider, Jessica J. Lin, Alice T. Shaw
Summary: Shaw and colleagues discuss the oncogenic roles of ALK in lung cancer, targeting approaches and the mechanisms underlying acquired resistance to ALK-directed therapy. Anaplastic lymphoma kinase (ALK) is a potent oncogenic driver in lung cancer. ALK tyrosine kinase inhibitors yield significant benefit in patients with ALK fusion-positive (ALK(+)) lung cancers; yet the durability of response is limited by drug resistance. Elucidation of on-target resistance mechanisms has facilitated the development of next-generation ALK inhibitors, but overcoming ALK-independent resistance mechanisms remains a challenge. In this Review, we discuss the molecular underpinnings of acquired resistance to ALK-directed therapy and highlight new treatment approaches aimed at inducing long-term remission in ALK(+) disease.
Meeting Abstract
Oncology
M. Hoejgaard, A. Drilon, J. J. Lin, S. Kummar, D. S. W. Tan, J. Patel, S. Leyvraz, V. Moreno Garcia, L. S. Rosen, B. Solomon, J. Yachnin, Y. Liu, M-S. Dai, R. Norenberg, D-I. Burcoveanu, L. Yun, G. Beckmann, C. E. Mussi, L. Shen
JOURNAL OF THORACIC ONCOLOGY
(2023)
Meeting Abstract
Oncology
M. L. Johnson, S-H. I. Ou, E. Felip, C. Baik, B. Besse, J. Mazieres, D. R. Camidge, S. Gadgeel, A. Drilon, Y. Y. Elamin, G. Liu, J. E. Reuss, T. Kehrig, H. E. Pelish, V. Zhu, J. J. Lin
JOURNAL OF THORACIC ONCOLOGY
(2023)
Meeting Abstract
Oncology
Carolyn Muller, Marya F. Chaney, Justine Vanessa Cohen, Tina Garyantes, Jessica Jiyeong Lin, Patricia LoRusso, Alain C. Mita, Monica M. Mita, Christopher Natale, Marlana M. Orloff, Kyriakos P. Papadopoulos, Sapna Pradyuman Patel, Jordi Rodon Ahnert
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Or Kalchiem-Dekel, Christina J. Falcon, Christine M. Bestvina, Dazhi Liu, Lauren A. Kaplanis, Clare Wilhelm, Jordan Eichholz, Guilherme Harada, Lori J. Wirth, Robert P. Lee, David Kadosh, Robin B. Mendelsohn, Jessica Donington, Justin F. Gainor, Alexander E. Drilon, Jessica Jiyeong Lin
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Maciej Jerzy Krzakowski, Shun Lu, Sophie Cousin, Egbert F. Smit, Christoph Springfeld, Koichi Goto, Pilar Garrido, Christine H. Chung, Jessica Jiyeong Lin, Victoria J. Bray, Bethany Pitcher, Harald Zeuner, Siddhartha Patel, Walter Bordogna, Hans Gelderblom
JOURNAL OF CLINICAL ONCOLOGY
(2022)
