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.
N1 - Funding Information:
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.
Funding Information:
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).
Publisher Copyright:
© 2022 by American Society of Clinical Oncology
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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U2 - 10.1200/PO.21.00418
DO - 10.1200/PO.21.00418
M3 - Article
C2 - 35085007
AN - SCOPUS:85124197787
VL - 6
JO - JCO Precision Oncology
JF - JCO Precision Oncology
SN - 2473-4284
M1 - e2100418
ER -
