Patient-reported Symptoms of Tenosynovial Giant Cell Tumors

Heather L Gelhorn, Sandra Tong, Kelly McQuarrie, Christina Vernon, Jennifer Hanlon, Grant Maclaine, William Lenderking, Xin Ye, Rebecca M Speck, Richard D Lackman, Susan V Bukata, John H Healey, Vicki L Keedy, Stephen P Anthony, Andrew J Wagner, Daniel D Von Hoff, Arun S Singh, Carlos R Becerra, Henry H Hsu, Paul S Lin, William D Tap, Heather L Gelhorn, Sandra Tong, Kelly McQuarrie, Christina Vernon, Jennifer Hanlon, Grant Maclaine, William Lenderking, Xin Ye, Rebecca M Speck, Richard D Lackman, Susan V Bukata, John H Healey, Vicki L Keedy, Stephen P Anthony, Andrew J Wagner, Daniel D Von Hoff, Arun S Singh, Carlos R Becerra, Henry H Hsu, Paul S Lin, William D Tap

Abstract

Purpose: Tenosynovial giant cell tumor (TGCT), a rare locally aggressive neoplasm of the synovium of joints and tendon sheaths, is associated with joint destruction, inflammation, pain, and swelling, in part due to colony-stimulating factor 1 receptor-bearing macrophages recruited to the tumor by genetic elevation of colony-stimulating factor 1 activity. The most common treatment is surgery, although promising pharmacologic treatments are in development. Patient-reported outcome (PRO) instruments are critical end points in demonstrating the clinical relevance of standard oncologic outcome measures and the overall impact of novel pharmacologic therapies in nonmalignant neoplastic conditions such as TGCT. The content validity of PROs relevant to patients with TGCT has not been formally investigated, and instruments to evaluate such outcomes do not exist for this condition.

Methods: PRO instruments of potential relevance were evaluated by using a literature review and by clinical and PRO experts. Patients with TGCT were recruited through clinical sites and the Internet for participation in qualitative research interviews to identify predominant symptoms and to test the relevance and content validity of several PRO measures. Select PRO measures were included in a Phase I clinical trial, and preliminary results of the PRO end points are reported descriptively.

Findings: Of the 22 subjects who participated in qualitative interviews, 73% were female, and their mean age was 42.5 years (range, 27-56 years). The TGCTs (19 diffuse and 3 localized) were located in the knee (n = 15), hip (n = 3), ankle (n = 2), elbow (n = 1), and forearm (n = 1). The most common symptoms cited were pain (82%), swelling (86%), stiffness (73%), reduced range of motion (64%), and joint instability (64%), which were consistent with clinical expert input and with the content of instruments chosen by PRO experts. The worst pain numeric rating scale, Patient Reported Outcomes Measurement Information System physical functioning items, and the Western Ontario and McMaster Universities Osteoarthritis Index, as well as a worst stiffness numeric rating scale developed for TGCT, were confirmed as meaningful measures of TGCT patient symptoms and were well understood in qualitative interviews. Results from the Phase I trial showed trends of improvement in both pain and stiffness over time.

Implications: This study is the first to gather information directly from patients with TGCT regarding their symptom experiences. Pain, stiffness, and physical functioning are important treatment outcomes in patients with TGCT. We have identified content-valid PRO measures of these concepts, which are included in an ongoing Phase III TGCT clinical trial with pexidartinib (PLX3397) (NCT02371369).

Keywords: PROMIS; giant cell tumors of the tendon sheath (GCT-TS); patient-reported outcomes (PRO); pigmented villonodular synovitis (PVNS); tenosynovial giant cell tumor (TGCT).

Conflict of interest statement

CONFLICTS OF INTEREST

G. Maclaine and X. Ye are employees of Daiichi Sankyo Development Ltd, which provided financial support for this research. S. Tong and P. Lin are employees of Plexxikon Inc, which provided financial support for this research. J.H. Healey is a paid consultant of Daiichi Sankyo Development Ltd. H. Hsu is a paid consultant of Plexxikon Inc. S. Anthony is a paid member of the Paradigm Medical Evidence Team and a paid consultant of Zymeworks Biopharmaceuticals. W. Taq is a paid consultant of Plexxikon and Daiichi Sankyo Development Ltd. The institutions of S. Bukata, D. Von Hoff, and V. Keedy received funding from Plexxikon for conducting the study for this work. D. Von Hoff is a paid consultant of Five Prime Therapeutics. H. Gelhorn, K. McQuarrie, C. Vernon, J. Hanlon, W. Lenderking, and R. Speck participated in this project as employees of Evidera, a company which performs work for hire for multiple pharmaceutical and device companies in outcomes research. K. McQuarrie is currently employed by Janssen. A. Wagner, A. Singh, C. Becerra, J. Hanlon, and R. Lackman have no conflicts of interest related to this work to report.

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Mean change from baseline: pain numeric rating scale (NRS).
Figure 2
Figure 2
Mean change from baseline: stiffness numeric rating scale (NRS).
Figure 3
Figure 3
Scatterplot of percent change in tumor size according to percent change in numeric rating scale pain score: baseline to week 25. Tumor size was assessed by using local Response Evaluation Criteria in Solid Tumors version 1.1 guidelines.
Figure 4
Figure 4
Scatterplot of percent change in tumor size according to percent change in numeric rating scale stiffness score: baseline to week 25. Tumor size was assessed by using local Response Evaluation Criteria in Solid Tumors version 1.1 guidelines.

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Source: PubMed

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