Larotrectinib Treatment for Patients With TRK Fusion-Positive Salivary Gland Cancers

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; David S. Hong; Nicoletta Brega; Alexander Drilon

doi:10.1093/oncolo/oyac080

Larotrectinib Treatment for Patients With TRK Fusion-Positive Salivary Gland Cancers

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, David S. Hong, Nicoletta Brega, Alexander Drilon

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

20 Scopus citations

Abstract

BACKGROUND: Larotrectinib is a first-in-class, highly selective, and central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for the treatment of adult and pediatric patients with TRK fusion cancer. We report the efficacy and safety of larotrectinib in patients with TRK fusion-positive salivary gland cancers.

PATIENTS AND METHODS: Patients with TRK fusion-positive salivary gland cancer treated with larotrectinib were identified from two clinical trials (NCT02122913 and NCT02576431). Patients received larotrectinib 100 mg twice daily (BID) except for one patient who received 150 mg BID in the phase I trial. The primary endpoint was objective response rate (ORR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1.

RESULTS: At the data cut-off (July 20, 2020), 24 patients with TRK fusion-positive salivary gland cancer had been treated. The most common histologies were secretory carcinoma (54%), adenocarcinoma (25%), and mucoepidermoid carcinoma (13%). All 24 patients had an ETV6-NTRK3 gene fusion. The ORR was 92% (95% confidence interval, 73-99). Best overall response was complete response in three (13%) patients, partial response in 19 (79%), and progressive disease in two (8%). The rate of progression-free survival at 24 months was 78% (median follow-up 30.9 months). Most treatment-related adverse events (AEs) were grade 1-2, and no patients discontinued treatment due to AEs.

CONCLUSION: Larotrectinib demonstrated robust and durable efficacy in patients with TRK fusion-positive salivary gland tumors of various histologies, and a favorable safety profile. These findings support NTRK gene fusion testing in patients with advanced salivary gland cancers.

CLINICALTRIALS.GOV NUMBERS: NCT02122913 and NCT02576431.

Original language	English
Pages (from-to)	e779-e788
Journal	Oncologist
Volume	29
Issue number	6
DOIs	https://doi.org/10.1093/oncolo/oyac080
State	Published - Jun 2024

Keywords

NTRK
TRK
gene fusion
larotrectinib
salivary gland tumors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/oncolo/oyac080

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Le, X., Baik, C., Bauman, J., Gilbert, J., Brose, M. S., Grilley-Olson, J. E., Patil, T., McDermott, R., Raez, L. E., Johnson, J. M., Shen, L., Tahara, M., Ho, A. L., Norenberg, R., Dima, L., Hong, D. S., Brega, N., & Drilon, A. (2024). Larotrectinib Treatment for Patients With TRK Fusion-Positive Salivary Gland Cancers. Oncologist, 29(6), e779-e788. https://doi.org/10.1093/oncolo/oyac080

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title = "Larotrectinib Treatment for Patients With TRK Fusion-Positive Salivary Gland Cancers",

abstract = "BACKGROUND: Larotrectinib is a first-in-class, highly selective, and central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for the treatment of adult and pediatric patients with TRK fusion cancer. We report the efficacy and safety of larotrectinib in patients with TRK fusion-positive salivary gland cancers.PATIENTS AND METHODS: Patients with TRK fusion-positive salivary gland cancer treated with larotrectinib were identified from two clinical trials (NCT02122913 and NCT02576431). Patients received larotrectinib 100 mg twice daily (BID) except for one patient who received 150 mg BID in the phase I trial. The primary endpoint was objective response rate (ORR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS: At the data cut-off (July 20, 2020), 24 patients with TRK fusion-positive salivary gland cancer had been treated. The most common histologies were secretory carcinoma (54%), adenocarcinoma (25%), and mucoepidermoid carcinoma (13%). All 24 patients had an ETV6-NTRK3 gene fusion. The ORR was 92% (95% confidence interval, 73-99). Best overall response was complete response in three (13%) patients, partial response in 19 (79%), and progressive disease in two (8%). The rate of progression-free survival at 24 months was 78% (median follow-up 30.9 months). Most treatment-related adverse events (AEs) were grade 1-2, and no patients discontinued treatment due to AEs.CONCLUSION: Larotrectinib demonstrated robust and durable efficacy in patients with TRK fusion-positive salivary gland tumors of various histologies, and a favorable safety profile. These findings support NTRK gene fusion testing in patients with advanced salivary gland cancers.CLINICALTRIALS.GOV NUMBERS: NCT02122913 and NCT02576431.",

keywords = "NTRK, TRK, gene fusion, larotrectinib, salivary gland tumors",

author = "Xiuning Le and Christina Baik and Jessica Bauman and Jill Gilbert and Brose, {Marcia S.} and Grilley-Olson, {Juneko E.} and Tejas Patil and Ray McDermott and Raez, {Luis E.} and Johnson, {Jennifer M.} and Lin Shen and Makoto Tahara and Ho, {Alan L.} and Ricarda Norenberg and Laura Dima and Hong, {David S.} and Nicoletta Brega and Alexander Drilon",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2022.",

year = "2024",

month = jun,

doi = "10.1093/oncolo/oyac080",

language = "English",

volume = "29",

pages = "e779--e788",

journal = "Oncologist",

issn = "1083-7159",

publisher = "Oxford University Press",

number = "6",

}

Le, X, Baik, C, Bauman, J, Gilbert, J, Brose, MS, Grilley-Olson, JE, Patil, T, McDermott, R, Raez, LE, Johnson, JM, Shen, L, Tahara, M, Ho, AL, Norenberg, R, Dima, L, Hong, DS, Brega, N & Drilon, A 2024, 'Larotrectinib Treatment for Patients With TRK Fusion-Positive Salivary Gland Cancers', Oncologist, vol. 29, no. 6, pp. e779-e788. https://doi.org/10.1093/oncolo/oyac080

TY - JOUR

T1 - Larotrectinib Treatment for Patients With TRK Fusion-Positive Salivary Gland Cancers

AU - Le, Xiuning

AU - Baik, Christina

AU - Bauman, Jessica

AU - Gilbert, Jill

AU - Brose, Marcia S.

AU - Grilley-Olson, Juneko E.

AU - Patil, Tejas

AU - McDermott, Ray

AU - Raez, Luis E.

AU - Johnson, Jennifer M.

AU - Shen, Lin

AU - Tahara, Makoto

AU - Ho, Alan L.

AU - Norenberg, Ricarda

AU - Dima, Laura

AU - Hong, David S.

AU - Brega, Nicoletta

AU - Drilon, Alexander

PY - 2024/6

Y1 - 2024/6

N2 - BACKGROUND: Larotrectinib is a first-in-class, highly selective, and central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for the treatment of adult and pediatric patients with TRK fusion cancer. We report the efficacy and safety of larotrectinib in patients with TRK fusion-positive salivary gland cancers.PATIENTS AND METHODS: Patients with TRK fusion-positive salivary gland cancer treated with larotrectinib were identified from two clinical trials (NCT02122913 and NCT02576431). Patients received larotrectinib 100 mg twice daily (BID) except for one patient who received 150 mg BID in the phase I trial. The primary endpoint was objective response rate (ORR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS: At the data cut-off (July 20, 2020), 24 patients with TRK fusion-positive salivary gland cancer had been treated. The most common histologies were secretory carcinoma (54%), adenocarcinoma (25%), and mucoepidermoid carcinoma (13%). All 24 patients had an ETV6-NTRK3 gene fusion. The ORR was 92% (95% confidence interval, 73-99). Best overall response was complete response in three (13%) patients, partial response in 19 (79%), and progressive disease in two (8%). The rate of progression-free survival at 24 months was 78% (median follow-up 30.9 months). Most treatment-related adverse events (AEs) were grade 1-2, and no patients discontinued treatment due to AEs.CONCLUSION: Larotrectinib demonstrated robust and durable efficacy in patients with TRK fusion-positive salivary gland tumors of various histologies, and a favorable safety profile. These findings support NTRK gene fusion testing in patients with advanced salivary gland cancers.CLINICALTRIALS.GOV NUMBERS: NCT02122913 and NCT02576431.

AB - BACKGROUND: Larotrectinib is a first-in-class, highly selective, and central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for the treatment of adult and pediatric patients with TRK fusion cancer. We report the efficacy and safety of larotrectinib in patients with TRK fusion-positive salivary gland cancers.PATIENTS AND METHODS: Patients with TRK fusion-positive salivary gland cancer treated with larotrectinib were identified from two clinical trials (NCT02122913 and NCT02576431). Patients received larotrectinib 100 mg twice daily (BID) except for one patient who received 150 mg BID in the phase I trial. The primary endpoint was objective response rate (ORR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS: At the data cut-off (July 20, 2020), 24 patients with TRK fusion-positive salivary gland cancer had been treated. The most common histologies were secretory carcinoma (54%), adenocarcinoma (25%), and mucoepidermoid carcinoma (13%). All 24 patients had an ETV6-NTRK3 gene fusion. The ORR was 92% (95% confidence interval, 73-99). Best overall response was complete response in three (13%) patients, partial response in 19 (79%), and progressive disease in two (8%). The rate of progression-free survival at 24 months was 78% (median follow-up 30.9 months). Most treatment-related adverse events (AEs) were grade 1-2, and no patients discontinued treatment due to AEs.CONCLUSION: Larotrectinib demonstrated robust and durable efficacy in patients with TRK fusion-positive salivary gland tumors of various histologies, and a favorable safety profile. These findings support NTRK gene fusion testing in patients with advanced salivary gland cancers.CLINICALTRIALS.GOV NUMBERS: NCT02122913 and NCT02576431.

KW - NTRK

KW - TRK

KW - gene fusion

KW - larotrectinib

KW - salivary gland tumors

UR - http://www.scopus.com/inward/record.url?scp=85194266736&partnerID=8YFLogxK

U2 - 10.1093/oncolo/oyac080

DO - 10.1093/oncolo/oyac080

M3 - Article

C2 - 35536733

AN - SCOPUS:85194266736

SN - 1083-7159

VL - 29

SP - e779-e788

JO - Oncologist

JF - Oncologist

IS - 6

ER -

Larotrectinib Treatment for Patients With TRK Fusion-Positive Salivary Gland Cancers

Abstract

Keywords

UN SDGs

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