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
5189 - Association between serum HGF levels and neutrophil counts in small cell lung cancer and their impact on survival
Presenter: Laura Moliner
Session: Poster Display session 1
Resources:
Abstract
3539 - Prognostic role of RLF/MYCL1 and circPVT1 in SCLC.
Presenter: Clelia Tiziana Storlazzi
Session: Poster Display session 1
Resources:
Abstract
3438 - High-biologically effective dose radiotherapy improve the survival of small cell lung cancer patients with brain metastases: a propensity-matching analysis
Presenter: Qingyang Zhuang
Session: Poster Display session 1
Resources:
Abstract
3232 - Phase 1 open-label study evaluating the safety, pharmacokinetics, and preliminary efficacy of ABBV-181 and rovalpituzumab tesirine (ROVA-T) in patients with small cell lung cancer
Presenter: Emiliano Calvo
Session: Poster Display session 1
Resources:
Abstract
3633 - Activity of the novel Aurora kinase B inhibitor AZD2811 in biomarker-defined models of small cell lung cancer
Presenter: Carminia Maria Della Corte
Session: Poster Display session 1
Resources:
Abstract
3745 - Multi-level proteomics identifies FABP5 as a primary chemoresistance mediator in extensive-stage small cell lung cancer
Presenter: Yamei Chen
Session: Poster Display session 1
Resources:
Abstract
5049 - CLEPSIDRA trial: a pilot, biomarker-guided study to assess safety, tolerability, dose finding and efficacy of iadademstat in combination with platinum-etoposide in patients with relapsed, extensive-stage small cell lung cancer
Presenter: Alejandro Navarro Mendivil
Session: Poster Display session 1
Resources:
Abstract
5997 - Phased Avelumab combined with chemotherapy as first-line treatment for patients with advanced small-cell lung cancer (SCLC): The PAVE study, a Hellenic Cooperative Oncology Group Study
Presenter: Helena Linardou
Session: Poster Display session 1
Resources:
Abstract
4502 - Tobacco use in lung cáncer (LC) patients (p) in Spain
Presenter: Enric Carcereny Costa
Session: Poster Display session 1
Resources:
Abstract
4369 - Biomarker testing of lung cancer in Spain
Presenter: Delvys Rodriguez Abreu
Session: Poster Display session 1
Resources:
Abstract