ETA2022 Oral Presentations Oral Session 3: Advanced Thyroid Cancer (5 abstracts)
Entrectinib in patients with ntrk fusion-positive (ntrk-fp) thyroid cancer: Updated data from startrk-2
Daniel W Bowles 1 , Lyudmila Bazhenova 2 , Ségolène Hescot 3 , Gunnar Folprecht 4 , Haruko Daga 5 , Erminia Massarelli 6 , Anthony P Conley 7 , Livia Lamartina 8 , Jessica Lin 9 , Eugene Ahn 10 , Stuart Osborne 11 , Sebastian Heinzmann 11 & Daniel Carrizosa 12
1Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, Co, United States; 2Moores Cancer Center, Department of Medicine, University of California San Diego, San Diego, Ca, USA, San Diego, Ca, United States; 3Department of Drug Development and Innovation (D3i), Institut Curie, Paris & Saint-Cloud, France; 4Medical Department, University Hospital Carl Gustav Carus, Dresden, Germany; 5Department of Medical Oncology, Osaka City General Hospital, Osaka, Japan; 6Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, Ca, United States; 7Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States; 8Gustave Roussy, Département D’imagerie Médicale, Service de Médecine Nucléaire et Cancérologie Endocrinienne, Villejuif, France; 9Department of Medicine, Massachusetts General Hospital Cancer Center, Boston, MA, United States; 10Cancer Treatment Centers of America, Chicago, Il, United States; 11F. Hoffmann-La Roche Limited, Basel, Switzerland; 12Department of Hematology/Oncology, Levine Cancer Institute, Charlotte, Nc, United States
Objectives: NTRK gene fusions are oncogenic drivers in many solid tumours, including thyroid cancers. In the phase 2 study STARTRK-2 (NCT02568267), entrectinib (a CNS-active tropomyosin receptor kinase [TRK] inhibitor) demonstrated efficacy in patients with NTRK-fp thyroid cancer (objective response rate [ORR]: 40%; clinical cut-off: 31 Oct 2018; n=5). We report updated data from a larger cohort with longer follow-up.
Methods: Adult patients with TRK-inhibitor naïve, locally advanced/metastatic NTRK-fp thyroid cancer, with or without baseline CNS metastases, were enrolled. Tumour responses were assessed by blinded independent central review (BICR) per RECIST v1.1 at Week 4 and every 8 weeks thereafter. Primary endpoints: ORR and duration of response (DoR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), intracranial (IC) efficacy and safety. Enrolment cut-off: 31 July 2019; clinical cut-off: 31 August 2020.
Results: The efficacy-evaluable population included 13 patients with ≥1 year of follow-up: 10 (77%) had papillary and three (23%) had other types of thyroid cancers. Median age was 55.0 years (range: 26–78); 7 patients (54%) had received ≥2 prior lines of therapy; and 7 patients (54%) had investigator-assessed baseline CNS metastases. Median survival follow-up was 36.1 months. Responses for all patients and patients with papillary NTRK-fp thyroid cancer are shown in the Table. Median DoR, PFS and OS for all patients were 13.2 months (95% CI: 7.9–NE), 19.9 months (95% CI: 6.5–33.8) and 19.9 months (95% CI: 14.5–NE), respectively. In patients with BICR-assessed baseline CNS metastases (n=6), IC-ORR was 50% (3/6; 95% CI: 11.8–88.2) and median IC-PFS was 15.0 months (95% CI: 6.3–NE). In the safety-evaluable population (n=16; all treated patients), 10 patients (63%) had a Grade ≥3 treatment-related adverse event (TRAE). There were two deaths (13%) due to TRAEs. TRAEs leading to dose reduction, interruption and discontinuation occurred in 31%, 38% and 19% of patients, respectively.
| NTRK-fp thyroid cancer | ||
| All patients (n=13) | Papillary thyroid cancer (n=10) | |
| ORR, n (%) 95% CI | 7 (54) 25.1–80.8 | 5 (50) 18.7–81.3 |
| Complete response (CR) | 1 (8) | 1 (10) |
| Partial response | 6 (46) | 4 (40) |
| Stable disease | 2 (15) | 2 (20) |
| Progressive disease (PD) | 1 (8) | 1 (10) |
| Non-CR/non-PD | 1 (8) | 0 |
| Missing/unevaluable | 2 (15) | 2 (20) |
Conclusions: In this updated analysis with more than twice the number of patients previously reported, ORR was numerically higher compared with the prior analysis and entrectinib demonstrated durable systemic and IC responses. No new safety signals were identified.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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