Format

Send to

Choose Destination
Br J Cancer. 2018 Jan;118(2):181-188. doi: 10.1038/bjc.2017.402. Epub 2017 Nov 21.

Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response.

Author information

1
Department of Medical Oncology, The Christie NHS Foundation Trust (ENETS Centre of Excellence), Manchester M20 4BX, UK.
2
Faculty of Medical, Biological and Human Sciences, University of Manchester, Manchester M13 9GB, UK.
3
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
4
Department of Gastroenterology, Cliniques Universitaires Saint-Luc, Bruxelles 1200, Belgium.
5
University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA.
6
Paoli-Calmettes Institute, Marseille 13009, France.
7
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.
8
Flatiron Health, New York, NY 10010, USA.
9
Department of Medical Oncology, Hospices Civils de Lyon Edouard Herriot Hospital, University of Lyon, Lyon 69002, France.
10
Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
11
Department of Medical Oncology, Beaujon University Hospital, Paris 92110, France.
12
Department of Medical Oncology, Groupe Hospitalier Paris Saint-Joseph, Paris 75014, France.
13
Institute of Cancer Sciences, University of Manchester, Manchester M204BX, UK.

Abstract

BACKGROUND:

Sunitinib prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumours (pNET). Response Evaluation Criteria in Solid Tumors (RECIST)-defined partial responses (PR; classically defined as ⩾30% size decrease from baseline) are infrequent.

METHODS:

Individual data of pNET patients from the phase II [NCT00056693] and pivotal phase III [NCT00428597] trials of sunitinib were analysed in this investigator-initiated, post hoc study. The primary objective was to determine the optimal RECIST (v.1.0) response cut-off value to identify patients who were progression-free at 11 months (median PFS in phase III trial); and the most informative time-point (highest area under the curve (AUC) by receiver operating characteristic (ROC) analysis and logistic regression) for prediction of benefit (PFS) from sunitinib.

RESULTS:

Data for 237 patients (85 placebo; 152 sunitinib (n=66.50 mg '4-weeks on/2-weeks off' schedule; n=86 '37.5 mg continuous daily dosing (CDD)')) and 788 scans were analysed. The median PFS for sunitinib and placebo were 9.3 months (95% CI 7.6-12.2) and 5.4 months (95% CI 3.5-6.01), respectively (hazard ratio (HR) 0.43 (95% CI 0.29-0.62); P<0.001). A PR was seen in 19 patients (13%) on sunitinib; the median change in the sum of the lesions (vs baseline) was -12.8% (range -100 to +36.4). Month 7 was the most informative time-point (AUC 0.78 (95% CI 0.66-0.9); odds ratio 1.05 (95% CI 1.01-1.08), P=0.002). Reduction of 10% (vs baseline) achieved the highest sensitivity (50%) and specificity (82%), amongst cut-offs tested. A 10% reduction in marker lesions was associated with improved PFS in the whole sunitinib population (HR 0.55 (95 CI 0.3-0.9); P=0.04); mostly in patients on sunitinib CDD (HR 0.33 (95% CI 0.2-0.7); P=0.005). A 10% reduction in marker lesions (P=0.034) and sunitinib treatment (P=0.012) independently impacted on PFS (multivariable analysis).

CONCLUSIONS:

A 10% reduction within marker lesions identifies pNET patients benefiting from sunitinib treatment with implications for maintenance of dose intensity and future trial design.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center