Larotrectinib versus Prior Therapies in Tropomyosin Receptor Kinase Fusion Cancer: An Intra-Patient Comparative Analysis
Randomized controlled basket trials investigating drugs targeting a rare molecular alteration are challenging. Using patients as their own control overcomes some of these challenges. Growth modulation index (GMI) is the ratio of progression-free survival (PFS) on the current therapy to time to progr...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/11/3246 |
| _version_ | 1797548876013502464 |
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| author | Antoine Italiano Shivani Nanda Andrew Briggs Jesus Garcia-Foncillas Ulrik Lassen Gilles Vassal Shivaani Kummar Cornelis M. van Tilburg David S. Hong Theodore W. Laetsch Karen Keating John A. Reeves Marc Fellous Barrett H. Childs Alexander Drilon David M. Hyman |
| author_facet | Antoine Italiano Shivani Nanda Andrew Briggs Jesus Garcia-Foncillas Ulrik Lassen Gilles Vassal Shivaani Kummar Cornelis M. van Tilburg David S. Hong Theodore W. Laetsch Karen Keating John A. Reeves Marc Fellous Barrett H. Childs Alexander Drilon David M. Hyman |
| author_sort | Antoine Italiano |
| collection | DOAJ |
| description | Randomized controlled basket trials investigating drugs targeting a rare molecular alteration are challenging. Using patients as their own control overcomes some of these challenges. Growth modulation index (GMI) is the ratio of progression-free survival (PFS) on the current therapy to time to progression (TTP) on the last prior line of therapy; GMI ≥ 1.33 is considered a threshold of meaningful clinical activity. In a retrospective, exploratory analysis among patients with advanced tropomyosin receptor kinase (TRK) fusion cancer treated with the selective TRK inhibitor larotrectinib who received ≥1 prior line of therapy for locally advanced/metastatic disease, we determined the proportion of patients with GMI ≥ 1.33; patients who had not progressed by data cut-off were censored for PFS. Among 72 eligible patients, median GMI was 2.68 (range 0.01–48.75). Forty-seven patients (65%) had GMI ≥ 1.33; 13/25 patients (52%) with GMI < 1.33 had not yet progressed on larotrectinib. Kaplan–Meier estimates showed a median GMI of 6.46. The probability of attaining GMI ≥ 1.33 was 0.75 (95% confidence interval (CI), 0.65–0.85). Median TTP on previous treatment was 3.0 months (95% CI, 2.6–4.4). Median PFS on larotrectinib was not estimable ((NE); 95% CI, NE; hazard ratio, 0.220 (95% CI, 0.146–0.332)). This analysis suggests larotrectinib improves PFS for patients with TRK fusion cancer compared with prior therapy. |
| first_indexed | 2024-03-10T15:07:00Z |
| format | Article |
| id | doaj.art-5dcfa005b9144647bcf75c9ad329930b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T15:07:00Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5dcfa005b9144647bcf75c9ad329930b2023-11-20T19:42:40ZengMDPI AGCancers2072-66942020-11-011211324610.3390/cancers12113246Larotrectinib versus Prior Therapies in Tropomyosin Receptor Kinase Fusion Cancer: An Intra-Patient Comparative AnalysisAntoine Italiano0Shivani Nanda1Andrew Briggs2Jesus Garcia-Foncillas3Ulrik Lassen4Gilles Vassal5Shivaani Kummar6Cornelis M. van Tilburg7David S. Hong8Theodore W. Laetsch9Karen Keating10John A. Reeves11Marc Fellous12Barrett H. Childs13Alexander Drilon14David M. Hyman15Early Phase Trials Unit, Institut Bergonie, 33000 Bordeaux, FranceBayer HealthCare Pharmaceuticals, Inc., Whippany, NJ 07981, USALondon School of Hygiene & Tropical Medicine, Bloomsbury, London WC1E 7HT, UKOncoHealth Institute, University Hospital Fundación Jiménez Díaz, 28040 Madrid, SpainDepartment of Oncology, Rigshospitalet, 2100 Copenhagen, DenmarkInstitut Gustave Roussy, 94800 Villejuif Cedex, FranceStanford Cancer Institute, Stanford University, Palo Alto, CA 94304, USAHopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyInvestigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pediatrics and Harold C, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center/Children’s Health, Dallas, TX 75390, USABayer HealthCare Pharmaceuticals, Inc., Whippany, NJ 07981, USABayer HealthCare Pharmaceuticals, Inc., Whippany, NJ 07981, USABayer HealthCare Pharmaceuticals, Inc., Whippany, NJ 07981, USABayer HealthCare Pharmaceuticals, Inc., Whippany, NJ 07981, USAMemorial Sloan Kettering Cancer Center, New York, NY 10065, USAMemorial Sloan Kettering Cancer Center, New York, NY 10065, USARandomized controlled basket trials investigating drugs targeting a rare molecular alteration are challenging. Using patients as their own control overcomes some of these challenges. Growth modulation index (GMI) is the ratio of progression-free survival (PFS) on the current therapy to time to progression (TTP) on the last prior line of therapy; GMI ≥ 1.33 is considered a threshold of meaningful clinical activity. In a retrospective, exploratory analysis among patients with advanced tropomyosin receptor kinase (TRK) fusion cancer treated with the selective TRK inhibitor larotrectinib who received ≥1 prior line of therapy for locally advanced/metastatic disease, we determined the proportion of patients with GMI ≥ 1.33; patients who had not progressed by data cut-off were censored for PFS. Among 72 eligible patients, median GMI was 2.68 (range 0.01–48.75). Forty-seven patients (65%) had GMI ≥ 1.33; 13/25 patients (52%) with GMI < 1.33 had not yet progressed on larotrectinib. Kaplan–Meier estimates showed a median GMI of 6.46. The probability of attaining GMI ≥ 1.33 was 0.75 (95% confidence interval (CI), 0.65–0.85). Median TTP on previous treatment was 3.0 months (95% CI, 2.6–4.4). Median PFS on larotrectinib was not estimable ((NE); 95% CI, NE; hazard ratio, 0.220 (95% CI, 0.146–0.332)). This analysis suggests larotrectinib improves PFS for patients with TRK fusion cancer compared with prior therapy.https://www.mdpi.com/2072-6694/12/11/3246growth modulation indexlarotrectinib<i>NTRK</i> gene fusiontropomyosin receptor kinaseTRK fusion cancer |
| spellingShingle | Antoine Italiano Shivani Nanda Andrew Briggs Jesus Garcia-Foncillas Ulrik Lassen Gilles Vassal Shivaani Kummar Cornelis M. van Tilburg David S. Hong Theodore W. Laetsch Karen Keating John A. Reeves Marc Fellous Barrett H. Childs Alexander Drilon David M. Hyman Larotrectinib versus Prior Therapies in Tropomyosin Receptor Kinase Fusion Cancer: An Intra-Patient Comparative Analysis Cancers growth modulation index larotrectinib <i>NTRK</i> gene fusion tropomyosin receptor kinase TRK fusion cancer |
| title | Larotrectinib versus Prior Therapies in Tropomyosin Receptor Kinase Fusion Cancer: An Intra-Patient Comparative Analysis |
| title_full | Larotrectinib versus Prior Therapies in Tropomyosin Receptor Kinase Fusion Cancer: An Intra-Patient Comparative Analysis |
| title_fullStr | Larotrectinib versus Prior Therapies in Tropomyosin Receptor Kinase Fusion Cancer: An Intra-Patient Comparative Analysis |
| title_full_unstemmed | Larotrectinib versus Prior Therapies in Tropomyosin Receptor Kinase Fusion Cancer: An Intra-Patient Comparative Analysis |
| title_short | Larotrectinib versus Prior Therapies in Tropomyosin Receptor Kinase Fusion Cancer: An Intra-Patient Comparative Analysis |
| title_sort | larotrectinib versus prior therapies in tropomyosin receptor kinase fusion cancer an intra patient comparative analysis |
| topic | growth modulation index larotrectinib <i>NTRK</i> gene fusion tropomyosin receptor kinase TRK fusion cancer |
| url | https://www.mdpi.com/2072-6694/12/11/3246 |
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