Abstract 5243
Background
Randomized controlled trials are not feasible for rare cancer populations particularly when the investigational drug targets a molecular alteration shared by several tumor types with different natural histories. Innovative approaches that incorporate patients as their own control can be utilized in this setting. Growth Modulation Index (GMI) is the ratio of time to progression (TTP) with nth line of therapy (TTPn) to the most recent prior line of therapy (TTPn-1), and a GMI ≥1.33 has been proposed as a marker of meaningful clinical activity. We report here the GMI for patients (pts) diagnosed with TRK fusion cancer and treated with larotrectinib, a selective TRK inhibitor.
Methods
TRK fusion cancer pts enrolled in 3 clinical trials (NCT02122913, NCT02637687, NCT02576431) who have been on treatment for at least 6 months (or discontinued early) and had at least one prior line of systemic therapy in metastatic setting were eligible. GMI was calculated as a ratio of progression-free survival (PFS) with larotrectinib (PFSLaro) to TTP of the prior line of therapy (TTPn-1). PFS was determined by independent review committee (IRC) assessments using RECIST 1.1 criteria.
Results
As of a July 30, 2018 data cut, 53 pts (42 adults, 11 pediatric) were eligible. Sixteen pts (30.2%) had 2 prior therapies and 24 (45.3%) had ≥3 prior lines of therapy. Thirteen different tumor types were represented with the largest being soft tissue sarcoma (n = 12), lung cancer (n = 7), thyroid cancer (n = 6), and colon cancer (n = 6). The median GMI (IRC) was 2.87 (range: 0.01–48.75, Table). Thirty-five (66.0%) pts had a GMI ≥1.33. Five of 18 pts with a GMI <1.33 are still on treatment and non-progressive at the time of analysis.Table:
485P
GMI (PFSLarotrectinib/TTPprior_line) | IRC-assessed pts N = 53 |
---|---|
Mean (SD) | 6.00 (9.97) |
Median (min, max) | 2.87 (0.01, 48.75) |
GMI category, n (%) <1 ≥1 1 to 1.33 ≥1.33 ≥2 | 15 (28.3) 38 (71.7) 3 (5.7) 35 (66.0) 32 (60.4) |
Conclusions
TRK fusion cancer patients treated with larotrectinib had a clinically meaningful improvement in PFS compared to TTP on prior treatment as evidenced by a GMI >1.33 in two-thirds of evaluable patients.
Clinical trial identification
NCT02122913, NCT02637687, NCT02576431.
Editorial acknowledgement
Editorial assistance was provided by Michael Sheldon, PhD, of Scion, London, UK, funded by Bayer.
Legal entity responsible for the study
Bayer.
Funding
Bayer.
Disclosure
A. Italiano: Advisory / Consultancy: Bayer, Epizyme, ImmuneDesign, Lilly, Merck, MSD, Novartis, Roche; Research grant / Funding (institution): AstraZeneca, Bayer, Merck, MSD, Pharmamar, Roche. S. Nanda: Full / Part-time employment: Bayer. K. Keating: Full / Part-time employment: Bayer. B.H. Childs: Full / Part-time employment: Bayer. M. Fellous: Full / Part-time employment: Bayer. A. Drilon: Advisory / Consultancy: Loxo Oncology/Bayer, Ignyta, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Genentech/Roche, Takeda/Ariad/Millenium, Helsinn, Beigene, BergenBio, Hengrui Therapeutics, Exelixis, Bayer, Tyra; Research grant / Funding (self): Foundation Medicine; Licensing / Royalties: Wolters Kluwer; Honoraria (institution): Pfizer, Exelixis, GlaxoSmithKline, Teva, Taiho; Travel / Accommodation / Expenses: Merck; Advisory / Consultancy: MORE Health. D.M. Hyman: Advisory / Consultancy: Chugai Pharma, CytomX Therapeutics, Boehringer Ingelheim, AstraZeneca, Pfizer, Bayer Pharmaceuticals, Genentech / F. Hoffmann-La Roche; Research grant / Funding (self): Loxo Oncology, Bayer Pharmaceuticals, PUMA Biotechnology, AstraZeneca.
Resources from the same session
5995 - Invasive fungal diseases caused by rare pathogens in patients after hematopoietic stem cell transplantation (HSCT) & chemotherapy
Presenter: Yuliya Rogacheva
Session: Poster Display session 1
Resources:
Abstract
2961 - Safety and pharmacokinetics of novel CXCR4 antagonist YF-H-2015005 in the mobilization of hematopoietic stem cells in patients with non-Hodgkin's lymphoma
Presenter: Weiping Liu
Session: Poster Display session 1
Resources:
Abstract
5771 - Chemotherapy associated Hyponatremia in Hematological Malignancies: A retrospective study of 189 patients treated in a single medical center
Presenter: Vadim Lesan
Session: Poster Display session 1
Resources:
Abstract
1165 - Risk factors for Bacteremia-Associated Mortality of Aeromona sobria in Hematologic Malignancies
Presenter: Gabriel De la Cruz-Kú
Session: Poster Display session 1
Resources:
Abstract
5287 - Use of droplet digital polymerase chain reaction for detecting minimal residual disease: a prospective, multi-institutional study
Presenter: Hyunkyung Park
Session: Poster Display session 1
Resources:
Abstract
1886 - RUBIH2 — Use of NGS in haematological malignancies: from real world data to national recommendations, an innovative program to evaluate the impact of healthcare technology on patient care
Presenter: Severine Coquerelle
Session: Poster Display session 1
Resources:
Abstract
1940 - Outcomes of chronic myeloid leukemia with T315I mutation in the absence of targeted therapy or hematopoietic stem cell transplantation
Presenter: Nageswara Palukuri
Session: Poster Display session 1
Resources:
Abstract
1946 - Is bone marrow examination indispensible in chronic myeloid Leukemia at diagnosis ?
Presenter: Nageswara Palukuri
Session: Poster Display session 1
Resources:
Abstract
1904 - Incidence of Imatinib Resistance in Chronic Myeloid Leukemia (CML) Patients: Experience from Resource Poor Centre of Eastern India
Presenter: Debmalya Bhattacharyya
Session: Poster Display session 1
Resources:
Abstract
3245 - BCR-ABL transcript variant’s significance in chronic myeloid leukemia in chronic phase: Institutional experience from a developing country
Presenter: Siva Prasad
Session: Poster Display session 1
Resources:
Abstract