Efficacy and Safety of Larotrectinib in Patients With Tropomyosin Receptor Kinase Fusion–Positive Lung Cancers

Alexander Drilon; Daniel S.W. Tan; Ulrik N. Lassen; Serge Leyvraz; Yongmei Liu; Jyoti D. Patel; Lee Rosen; Benjamin Solomon; Ricarda Norenberg; Laura Dima; Nicoletta Brega; Lin Shen; Victor Moreno; Shivaani Kummar; Jessica J. Lin

doi:10.1200/PO.21.00418

Efficacy and Safety of Larotrectinib in Patients With Tropomyosin Receptor Kinase Fusion–Positive Lung Cancers

Alexander Drilon^*, Daniel S.W. Tan, Ulrik N. Lassen, Serge Leyvraz, Yongmei Liu, Jyoti D. Patel, Lee Rosen, Benjamin Solomon, Ricarda Norenberg, Laura Dima, Nicoletta Brega, Lin Shen, Victor Moreno, Shivaani Kummar, Jessica J. Lin

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

Abstract

PURPOSE Larotrectinib is a highly selective and CNS-active tropomyosin receptor kinase (TRK) inhibitor that has demonstrated efficacy across TRK fusion–positive cancers, regardless of the tumor type. The aim of this study was to assess the efficacy and safety of larotrectinib in patients with TRK fusion–positive lung cancers. MATERIALS AND METHODS Data from two global, multicenter, registrational clinical trials of patients treated with larotrectinib were analyzed: a phase II adult and young adult basket trial (NCT02576431) and a phase I adult trial (NCT02122913). The primary end point was objective response rate (ORR). RESULTS By July 20, 2020, 20 patients with TRK fusion–positive lung cancer had been treated. The ORR by investigator assessment among 15 evaluable patients was 73% (95% CI, 45 to 92); one (7%) patient had a complete response, 10 (67%) had a partial response, three (20%) had stable disease, and one (7%) had progressive disease as best response. The median duration of response, progression-free survival, and overall survival were 33.9 months (95% CI, 5.6 to 33.9), 35.4 months (95% CI, 5.3 to 35.4), and 40.7 months (95% CI, 17.2 to not estimable), respectively. Among patients with baseline CNS metastases, the ORR was 63% (95% CI, 25 to 91). Adverse events were mainly grade 1 or 2. CONCLUSION Larotrectinib is highly active with rapid and durable responses, extended survival benefit, and a favorable long-term safety profile in patients with advanced lung cancer harboring NTRK gene fusions, including those with CNS metastases. These findings support routine testing for NTRK fusions in patients with lung cancer.

Original language	English (US)
Article number	e2100418
Journal	JCO Precision Oncology
Volume	6
DOIs	https://doi.org/10.1200/PO.21.00418
State	Published - 2022

Funding

The authors would like to thank the patients, their families, and all investigators involved in this study. Medical writing support was provided by Francesca Murphy, and editorial support was provided by George Chappell, MSc, both of Scion, London, UK, supported by Bayer according to Good Publication Practice guidelines (https://www.acpjournals.org/ doi/10.7326/M15-0288). The sponsor was involved in the study design, collection, analysis, and interpretation of data, as well as data checking of information provided in the manuscript. However, ultimate responsibility for opinions, conclusions, and data interpretation lies with the authors. Supported by Bayer Healthcare and Loxo Oncology, Inc, a wholly owned subsidiary of Eli Lilly and Company. AD was supported in part by Cancer Center and RO1 grants from the National Institutes of Health (P30 CA008748, RO1 CA226864) and Nonna’s Garden. DT was supported in part by grants from the National Medical Research Council (NMRC; Singapore; NMRC/OFLCG/002-2018; NMRC/CSA/010/2019).

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Oncology
Cancer Research

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Drilon, A., Tan, D. S. W., Lassen, U. N., Leyvraz, S., Liu, Y., Patel, J. D., Rosen, L., Solomon, B., Norenberg, R., Dima, L., Brega, N., Shen, L., Moreno, V., Kummar, S., & Lin, J. J. (2022). Efficacy and Safety of Larotrectinib in Patients With Tropomyosin Receptor Kinase Fusion–Positive Lung Cancers. JCO Precision Oncology, 6, Article e2100418. https://doi.org/10.1200/PO.21.00418

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title = "Efficacy and Safety of Larotrectinib in Patients With Tropomyosin Receptor Kinase Fusion–Positive Lung Cancers",

abstract = "PURPOSE Larotrectinib is a highly selective and CNS-active tropomyosin receptor kinase (TRK) inhibitor that has demonstrated efficacy across TRK fusion–positive cancers, regardless of the tumor type. The aim of this study was to assess the efficacy and safety of larotrectinib in patients with TRK fusion–positive lung cancers. MATERIALS AND METHODS Data from two global, multicenter, registrational clinical trials of patients treated with larotrectinib were analyzed: a phase II adult and young adult basket trial (NCT02576431) and a phase I adult trial (NCT02122913). The primary end point was objective response rate (ORR). RESULTS By July 20, 2020, 20 patients with TRK fusion–positive lung cancer had been treated. The ORR by investigator assessment among 15 evaluable patients was 73% (95% CI, 45 to 92); one (7%) patient had a complete response, 10 (67%) had a partial response, three (20%) had stable disease, and one (7%) had progressive disease as best response. The median duration of response, progression-free survival, and overall survival were 33.9 months (95% CI, 5.6 to 33.9), 35.4 months (95% CI, 5.3 to 35.4), and 40.7 months (95% CI, 17.2 to not estimable), respectively. Among patients with baseline CNS metastases, the ORR was 63% (95% CI, 25 to 91). Adverse events were mainly grade 1 or 2. CONCLUSION Larotrectinib is highly active with rapid and durable responses, extended survival benefit, and a favorable long-term safety profile in patients with advanced lung cancer harboring NTRK gene fusions, including those with CNS metastases. These findings support routine testing for NTRK fusions in patients with lung cancer.",

author = "Alexander Drilon and Tan, {Daniel S.W.} and Lassen, {Ulrik N.} and Serge Leyvraz and Yongmei Liu and Patel, {Jyoti D.} and Lee Rosen and Benjamin Solomon and Ricarda Norenberg and Laura Dima and Nicoletta Brega and Lin Shen and Victor Moreno and Shivaani Kummar and Lin, {Jessica J.}",

note = "Publisher Copyright: {\textcopyright} 2022 by American Society of Clinical Oncology",

year = "2022",

doi = "10.1200/PO.21.00418",

language = "English (US)",

volume = "6",

journal = "JCO Precision Oncology",

issn = "2473-4284",

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TY - JOUR

T1 - Efficacy and Safety of Larotrectinib in Patients With Tropomyosin Receptor Kinase Fusion–Positive Lung Cancers

AU - Drilon, Alexander

AU - Tan, Daniel S.W.

AU - Lassen, Ulrik N.

AU - Leyvraz, Serge

AU - Liu, Yongmei

AU - Patel, Jyoti D.

AU - Rosen, Lee

AU - Solomon, Benjamin

AU - Norenberg, Ricarda

AU - Dima, Laura

AU - Brega, Nicoletta

AU - Shen, Lin

AU - Moreno, Victor

AU - Kummar, Shivaani

AU - Lin, Jessica J.

PY - 2022

Y1 - 2022

N2 - PURPOSE Larotrectinib is a highly selective and CNS-active tropomyosin receptor kinase (TRK) inhibitor that has demonstrated efficacy across TRK fusion–positive cancers, regardless of the tumor type. The aim of this study was to assess the efficacy and safety of larotrectinib in patients with TRK fusion–positive lung cancers. MATERIALS AND METHODS Data from two global, multicenter, registrational clinical trials of patients treated with larotrectinib were analyzed: a phase II adult and young adult basket trial (NCT02576431) and a phase I adult trial (NCT02122913). The primary end point was objective response rate (ORR). RESULTS By July 20, 2020, 20 patients with TRK fusion–positive lung cancer had been treated. The ORR by investigator assessment among 15 evaluable patients was 73% (95% CI, 45 to 92); one (7%) patient had a complete response, 10 (67%) had a partial response, three (20%) had stable disease, and one (7%) had progressive disease as best response. The median duration of response, progression-free survival, and overall survival were 33.9 months (95% CI, 5.6 to 33.9), 35.4 months (95% CI, 5.3 to 35.4), and 40.7 months (95% CI, 17.2 to not estimable), respectively. Among patients with baseline CNS metastases, the ORR was 63% (95% CI, 25 to 91). Adverse events were mainly grade 1 or 2. CONCLUSION Larotrectinib is highly active with rapid and durable responses, extended survival benefit, and a favorable long-term safety profile in patients with advanced lung cancer harboring NTRK gene fusions, including those with CNS metastases. These findings support routine testing for NTRK fusions in patients with lung cancer.

AB - PURPOSE Larotrectinib is a highly selective and CNS-active tropomyosin receptor kinase (TRK) inhibitor that has demonstrated efficacy across TRK fusion–positive cancers, regardless of the tumor type. The aim of this study was to assess the efficacy and safety of larotrectinib in patients with TRK fusion–positive lung cancers. MATERIALS AND METHODS Data from two global, multicenter, registrational clinical trials of patients treated with larotrectinib were analyzed: a phase II adult and young adult basket trial (NCT02576431) and a phase I adult trial (NCT02122913). The primary end point was objective response rate (ORR). RESULTS By July 20, 2020, 20 patients with TRK fusion–positive lung cancer had been treated. The ORR by investigator assessment among 15 evaluable patients was 73% (95% CI, 45 to 92); one (7%) patient had a complete response, 10 (67%) had a partial response, three (20%) had stable disease, and one (7%) had progressive disease as best response. The median duration of response, progression-free survival, and overall survival were 33.9 months (95% CI, 5.6 to 33.9), 35.4 months (95% CI, 5.3 to 35.4), and 40.7 months (95% CI, 17.2 to not estimable), respectively. Among patients with baseline CNS metastases, the ORR was 63% (95% CI, 25 to 91). Adverse events were mainly grade 1 or 2. CONCLUSION Larotrectinib is highly active with rapid and durable responses, extended survival benefit, and a favorable long-term safety profile in patients with advanced lung cancer harboring NTRK gene fusions, including those with CNS metastases. These findings support routine testing for NTRK fusions in patients with lung cancer.

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Efficacy and Safety of Larotrectinib in Patients With Tropomyosin Receptor Kinase Fusion–Positive Lung Cancers

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