Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 1

5243 - Growth modulation index (GMI) as a comparative measure of clinical activity of larotrectinib versus prior systemic treatments in adult and pediatric TRK fusion cancer patients

Date

28 Sep 2019

Session

Poster Display session 1

Topics

Clinical Research

Tumour Site

Presenters

Antoine Italiano

Citation

Annals of Oncology (2019) 30 (suppl_5): v159-v193. 10.1093/annonc/mdz244

Authors

A. Italiano1, S. Nanda2, K. Keating3, B.H. Childs4, M. Fellous5, A. Drilon6, D.M. Hyman6

Author affiliations

  • 1 Early Phase Trials Unit, Institute Bergonié, 33076 - Bordeaux/FR
  • 2 Biostatistics, Bayer HealthCare Pharmaceuticals, Inc., Whippany/US
  • 3 Heor, Bayer HealthCare Pharmaceuticals, Inc., Whippany/US
  • 4 Oncology, Bayer HealthCare Pharmaceuticals, Inc., Whippany/US
  • 5 Global Medical Affairs, Bayer HealthCare Pharmaceuticals, Inc., Whippany/US
  • 6 Department Of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, 10065 - New York/US

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

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 ≥215 (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.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.