1513P - Tumor growth rate analysis of progression-free survival (PFS) and overall survival (OS) for patients with metastatic and/or unresectable gastrointe...

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
GIST
Sarcoma
Presenter Christian Kappeler
Citation Annals of Oncology (2017) 28 (suppl_5): v521-v538. 10.1093/annonc/mdx387
Authors C. Kappeler1, A. Wagner2, G.D.S. Demetri3
  • 1Clinical Statistics, Global Clinical Oncology, Bayer AG, 13353 - Berlin/DE
  • 2Global Clinical Development, Bayer AG, 13353 - Berlin/DE
  • 3Center For Sarcoma And Bone Oncology, Dana-Farber Cancer Institute and Ludwig Center, Harvard Medical School, 02215 - Boston/US

Abstract

Background

In the randomized, controlled phase 3 GRID trial (NCT01271712), regorafenib (REG) significantly improved PFS versus placebo (PBO) in patients with advanced GIST (HR 0.268; P 

Methods

The primary endpoint of GRID was PFS; OS was a secondary endpoint. Target lesions were assessed by central radiologic review based on RECIST (v1.1). Changes in target lesions over time were approximated by a parabola-like 3-parametric model. eTGR was defined as the percentage change per month of the sum of target lesion diameters from the start of double-blind treatment. To explore the association between eTGR and PFS and OS, values of eTGR were split into quartiles (Q) separately by treatment arm. PFS (cut-off in 2012) and OS (cut-off in 2015) were compared in each subgroup population by median times derived from Kaplan–Meier curves and from modeling with a Weibull distribution.

Results

For PBO and REG, there is a nearly inverse relationship between eTGR and median times of PFS and OS from Q1 to Q4 eTGR. For the REG subgroup in Q1 eTGR, this trend is lost, as it has similar or worse median times than the subgroups around zero eTGR, which show the best prognosis.Table:

1513P

PBOREG
Q1Q2Q3Q4Q1Q2Q3Q4
Mean eTGR–0.0630.0640.1470.279–0.128–0.0220.0240.135
Median PFS*2.71.51.00.85.57.86.01.6
Median OS*45.521.812.39.729.128.917.411.5
*

By Weibull model of Kaplan–Meier curves; durations in months.

Conclusions

In this exploratory analysis, stabilization of tumor lesions at treatment start seems to be prognostic for better PFS and OS outcomes. A strong reduction of eTGR, which is seen for some REG patients, is not necessary for further disease stabilization and improvement. eTGR may be an additional efficacy parameter to consider when monitoring REG and other tyrosine kinase inhibitor (TKI) treatments in TKI-resistant GIST.

Clinical trial identification

NCT01271712

Legal entity responsible for the study

Bayer

Funding

Bayer

Disclosure

C. Kappeler, A. Wagner: Employment and Stock Ownership: Bayer AG.

\r\n

G.D.S. Demetri: Consulting/Advisory Role: Bayer, Pfizer, Novartis, Eli Lilly, EMD Serono, Sanofi, Janssen Oncology, PharmaMar, Daiichi Sankyo, ARIAD, Blueprint Medicines, Kolltan Pharmaceuticals, WIRB-Copermicus Group, ZIOPHARM Oncology, Polaris, Nektar, Genocea Biosciences, G1 Therapeutics, Caris Life Sciences, Adaptimmune, Kyocera, Eisai; Stock Ownership: Blueprint Medicines, G1 Therapeutics, Bessor Pharma, Caris Life Sciences, Champions Oncology, N-of-One; Research Funding: Novartis, Pfizer, Bayer, AbbVie, Janssen Oncology, Eisai, Amgen; Leadership: Blueprint Medicines; Other: Patents licensed to Novartis from Dana-Farber, with royalty paid to Dana-Farber.

Disclosure

C. Kappeler, A. Wagner: Employment and Stock Ownership: Bayer AG.

G.D.S. Demetri: Consulting/Advisory Role: Bayer, Pfizer, Novartis, Eli Lilly, EMD Serono, Sanofi, Janssen Oncology, PharmaMar, Daiichi Sankyo, ARIAD, Blueprint Medicines, Kolltan Pharmaceuticals, WIRB-Copermicus Group, ZIOPHARM Oncology, Polaris, Nektar, Genocea Biosciences, G1 Therapeutics, Caris Life Sciences, Adaptimmune, Kyocera, Eisai; Stock Ownership: Blueprint Medicines, G1 Therapeutics, Bessor Pharma, Caris Life Sciences, Champions Oncology, N-of-One; Research Funding: Novartis, Pfizer, Bayer, AbbVie, Janssen Oncology, Eisai, Amgen; Leadership: Blueprint Medicines; Other: Patents licensed to Novartis from Dana-Farber, with royalty paid to Dana-Farber.