Larotrectinib versus prior therapies in tropomyosin receptor kinase fusion cancer: An intra-patient comparative analysis Journal Article
| Authors: | Italiano, A.; Nanda, S.; Briggs, A.; Garcia-Foncillas, J.; Lassen, U.; Vassal, G.; Kummar, S.; van Tilburg, C. M.; Hong, D. S.; Laetsch, T. W.; Keating, K.; Reeves, J. A.; Fellous, M.; Childs, B. H.; Drilon, A.; Hyman, D. M. |
| Article Title: | Larotrectinib versus prior therapies in tropomyosin receptor kinase fusion cancer: An intra-patient comparative analysis |
| Abstract: | 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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. |
| Keywords: | osteosarcoma; adolescent; adult; child; controlled study; preschool child; young adult; unclassified drug; major clinical study; advanced cancer; pancreas cancer; gastrointestinal stromal tumor; melanoma; metastasis; progression free survival; breast cancer; lung cancer; retrospective study; diagnostic value; colon cancer; gene fusion; soft tissue sarcoma; bile duct carcinoma; thyroid cancer; salivary gland cancer; appendix cancer; clinical outcome; oncological parameters; tropomyosin; human; male; female; article; growth modulation index; larotrectinib; tropomyosin receptor kinase; tumor-related gene; trk fusion cancer; ntrk gene fusion; ntrk gene |
| Journal Title: | Cancers |
| Volume: | 12 |
| Issue: | 11 |
| ISSN: | 2072-6694 |
| Publisher: | MDPI |
| Date Published: | 2020-11-01 |
| Start Page: | 3246 |
| Language: | English |
| DOI: | 10.3390/cancers12113246 |
| PROVIDER: | scopus |
| PMCID: | PMC7692104 |
| PUBMED: | 33158040 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2020 -- Source: Scopus |
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