Pneumologie 2019; 73(S 01)
DOI: 10.1055/s-0039-1678033
Posterbegehung (P03) – Sektion Pneumologische Onkologie
NSCLC metastasiert, molekulare Treiber
Georg Thieme Verlag KG Stuttgart · New York

ENCORE: Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small Cell Lung Cancer (NSCLC)

DSY Abdulla
1   On Behalf of All Authors; Center of Integrated Oncology, University Hospital Cologne
,
RC Doebele
2   University of Colorado, Aurora
,
MJ Ahn
3   Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul
,
S Siena
4   Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, and Department of Oncology and Hemato-Oncology, Università Degli Studi DI Milano, Milan
,
A Drilon
5   Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York
,
MG Krebs
6   Division of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester
,
CC Lin
7   Department of Oncology, National Taiwan University, Taipei
,
F de Braud
8   Department of Medical Oncology, Fondazione Irccs Istituto Nazionale Dei Tumori, and Department of Medical Oncology, University of Milan
,
T John
9   Department of Medical Oncology, Olivia Newton John Cancer Research Institute, Melbourne
,
DSW Tan
10   Division of Medical Oncology, National Cancer Centre
,
T Seto
11   Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka
,
R Dziadziusko
12   Department of Oncology and Radiotherapy, Medical University of Gdansk
,
HT Arkenau
13   Sarah Cannon Research Institute, London
,
F Barlesi
14   Aix Marseille University, Assistance Publique-Hôpitaux de Marseille
,
C Rolfo
15   Phase I–early Clinical Trials Unit, Oncology Department, Antwerp University Hospital, Antwerp
,
J Wolf
16   Center for Integrated Oncology Köln-Bonn, University Hospital of Cologne
,
E Chow-Maneval
17   Ignyta, Inc., San Diego
,
PS Multani
17   Ignyta, Inc., San Diego
,
N Cui
18   Genentech, South San Francisco
,
T Riehl
18   Genentech, South San Francisco
,
BC Cho
19   Division of Medical Oncology, Yonsei Cancer Center, Seoul
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Publikationsverlauf

Publikationsdatum:
19. Februar 2019 (online)

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Background Entrectinib is a central nervous system (CNS) active, potent, and selective inhibitor of ROS1, TRKA/B/C and ALK. Entrectinib is more potent against ROS1 than crizotinib, the only agent currently approved for treatment of ROS1 -positive NSCLC. Interim data demonstrated that entrectinib was tolerable and achieved high objective response rates (ORR) in patients with ROS1 -positive, ROS1 inhibitor-naive NSCLC, including patients with baseline CNS disease.

Methods Phase 1/2 studies of entrectinib (ALKA, STARTRK-1, STARTRK-2; EudraCT 2012 – 000 148 – 88; NCT02097810; NCT02568267) enrolled patients with locally advanced or metastatic solid tumors. The safety-evaluable population included patients who received ≥ 1 dose of entrectinib. The integrated efficacy analysis included ROS1-positive NSCLC patients. Safety was assessed by monitoring adverse events (AEs), laboratory tests, and physical examination. Performed tumor scans were submitted for BICR using RECISTv1.1. Primary endpoints were ORR and DOR by BICR. Key secondary objectives were PFS, OS and safety. Additional endpoints were intracranial ORR, intracranial DOR, and PFS in patients with baseline CNS disease.

Results There were 53 efficacy-evaluable patients with treatment-naïve, ROS1-positive NSCLC. BICR ORR was 77.4% (95% CI 63.8 – 87.7) with complete responses in three patients (5.7%); median BICR DOR was 24.6 months (95% CI 11.4 – 34.8). Per baseline CNS status (as determined by investigator), median BICR PFS was 26.3 months (95% CI 15.7 – 36.6) and 13.6 months (95% CI 4.5–NR) for patients without (n = 30) and with CNS disease (n = 23), respectively. Intracranial ORR was 55.0% (95% CI 31.5 – 76.9) and median intracranial DOR was 12.9 months (95% CI 5.6–not reached [NR]) in patients with baseline CNS disease (n = 20). In the overall safety-evaluable population (n = 355), most treatment-related AEs were grade 1 – 2. 27.3% of patients required dose reduction, few discontinued treatment (3.9%) due to treatment-related AEs.

Conclusion Entrectinib was tolerable with a manageable safety profile and showed clinically meaningful, deep and durable systemic responses in ROS1 -positive NSCLC. Clinically meaningful intracranial activity was also demonstrated in patients with baseline CNS disease.