Surrogate Endpoints in Advanced Sarcoma Trials: a Meta-analysis

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Oct 24

PMID 30349653

Citations 4

Authors

Marion Savina

Saskia Litiere

Antoine Italiano

Tomasz Burzykowski

Franck Bonnetain

Sophie Gourgou

Virginie Rondeau

Jean-Yves Blay

Sophie Cousin

Florence Duffaud

Hans Gelderblom

Alessandro Gronchi

Ian Judson

Axel Le Cesne

Paul Lorigan

Joan Maurel

Winette van der Graaf

Jaap Verweij

Simone Mathoulin-Pelissier

Carine Bellera

Affiliations

Soon will be listed here.

Abstract

Background: Alternative endpoints to overall survival (OS) are frequently used to assess treatment efficacy in randomized controlled trials (RCT). Their properties in terms of surrogate outcomes for OS need to be assessed. We evaluated the surrogate properties of progression-free survival (PFS), time-to-progression (TTP) and time-to-treatment failure (TTF) in advanced soft tissue sarcomas (STS).

Results: A total of 21 trials originally met the selection criteria and 14 RCTs ( = 2846) were included in the analysis. Individual-level associations were moderate (highest for 12-month PFS: Spearman's rho = 0.66; 95% CI [0.63; 0.68]). Trial-level associations were ranked as low for the three endpoints as per the IQWiG criterion.

Materials And Methods: We performed a meta-analysis using individual-patient data (IPD). Phase II/III RCTs evaluating therapies for adults with advanced STS were eligible. We estimated the individual- and the trial-level associations between then candidate surrogates and OS. Statistical methods included weighted linear regression and the two-stage model introduced by Buyse and Burzykowski. The strength of the trial-level association was ranked according to the German Institute for Quality and Efficiency in Health Care (IQWiG) guidelines.

Conclusions: Our results do not support strong surrogate properties of PFS, TTP and TTF for OS in advanced STS.

Citing Articles

Cardiac events among patients with sarcoma treated with doxorubicin by method of infusion: A real-world database study.

Cranmer L, Hess L, Sugihara T, Muntz H Cancer Rep (Hoboken). 2022; 6(1):e1681.

PMID: 35852051 PMC: 9875654. DOI: 10.1002/cnr2.1681.

In search of effective therapies: the current landscape of phase II trials in patients with advanced soft tissue sarcoma.

Sobczuk P, Batruk H, Wojcik P, Iwaniak K, Kozak K, Rutkowski P J Cancer Res Clin Oncol. 2022; 149(7):2771-2782.

PMID: 35778653 DOI: 10.1007/s00432-022-04149-0.

Surrogate endpoints for overall survival in randomised controlled trials of localised osteosarcoma: A meta-analytic evaluation.

Tanaka K, Kawano M, Iwasaki T, Matsuda S, Itonaga I, Tsumura H Sci Rep. 2020; 10(1):8573.

PMID: 32444660 PMC: 7244479. DOI: 10.1038/s41598-020-65591-z.

A meta-analytic evaluation of the correlation between event-free survival and overall survival in randomized controlled trials of newly diagnosed Ewing sarcoma.

Tanaka K, Kawano M, Iwasaki T, Itonaga I, Tsumura H BMC Cancer. 2020; 20(1):379.

PMID: 32370741 PMC: 7201711. DOI: 10.1186/s12885-020-06871-9.

References

Kim C, Prasad V . Strength of Validation for Surrogate End Points Used in the US Food and Drug Administration's Approval of Oncology Drugs. Mayo Clin Proc. 2016; . PMC: 5104665. DOI: 10.1016/j.mayocp.2016.02.012. View

van der Graaf W, Blay J, Chawla S, Kim D, Bui-Nguyen B, Casali P . Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012; 379(9829):1879-86. DOI: 10.1016/S0140-6736(12)60651-5. View

Kim C, Prasad V . Cancer Drugs Approved on the Basis of a Surrogate End Point and Subsequent Overall Survival: An Analysis of 5 Years of US Food and Drug Administration Approvals. JAMA Intern Med. 2015; 175(12):1992-4. DOI: 10.1001/jamainternmed.2015.5868. View

Constantinidou A, van der Graaf W . The fate of new fosfamides in phase III studies in advanced soft tissue sarcoma. Eur J Cancer. 2017; 84:257-261. DOI: 10.1016/j.ejca.2017.07.043. View

Maurel J, Lopez-Pousa A, De Las Penas R, Fra J, Martin J, Cruz J . Efficacy of sequential high-dose doxorubicin and ifosfamide compared with standard-dose doxorubicin in patients with advanced soft tissue sarcoma: an open-label randomized phase II study of the Spanish group for research on sarcomas. J Clin Oncol. 2009; 27(11):1893-8. DOI: 10.1200/JCO.2008.19.2930. View

LeBlanc M, Tangen C . Surrogates for Survival or Other End Points in Oncology. JAMA Oncol. 2015; 2(2):263-4. DOI: 10.1001/jamaoncol.2015.4711. View

Taylor R, Elston J . The use of surrogate outcomes in model-based cost-effectiveness analyses: a survey of UK Health Technology Assessment reports. Health Technol Assess. 2009; 13(8):iii, ix-xi, 1-50. DOI: 10.3310/hta13080. View

Coindre J, Terrier P, Guillou L, Le Doussal V, Collin F, Ranchere D . Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer. 2001; 91(10):1914-26. DOI: 10.1002/1097-0142(20010515)91:10<1914::aid-cncr1214>3.0.co;2-3. View

Lorigan P, Verweij J, Papai Z, Rodenhuis S, Cesne A, Leahy M . Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.... J Clin Oncol. 2007; 25(21):3144-50. DOI: 10.1200/JCO.2006.09.7717. View

10.

Fayette J, Penel N, Chevreau C, Blay J, Cupissol D, Thyss A . Phase III trial of standard versus dose-intensified doxorubicin, ifosfamide and dacarbazine (MAID) in the first-line treatment of metastatic and locally advanced soft tissue sarcoma. Invest New Drugs. 2009; 27(5):482-9. DOI: 10.1007/s10637-008-9217-1. View

11.

Bui-Nguyen B, Ray-Coquard I, Chevreau C, Penel N, Bay J, Coindre J . High-dose chemotherapy consolidation for chemosensitive advanced soft tissue sarcoma patients: an open-label, randomized controlled trial. Ann Oncol. 2011; 23(3):777-784. DOI: 10.1093/annonc/mdr282. View

12.

Sridhara R, Johnson J, Justice R, Keegan P, Chakravarty A, Pazdur R . Review of oncology and hematology drug product approvals at the US Food and Drug Administration between July 2005 and December 2007. J Natl Cancer Inst. 2010; 102(4):230-43. DOI: 10.1093/jnci/djp515. View

13.

Buyse M, Molenberghs G, Burzykowski T, Renard D, Geys H . The validation of surrogate endpoints in meta-analyses of randomized experiments. Biostatistics. 2003; 1(1):49-67. DOI: 10.1093/biostatistics/1.1.49. View

14.

Bellera C, Penel N, Ouali M, Bonvalot S, Casali P, Nielsen O . Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†. Ann Oncol. 2014; 26(5):865-872. DOI: 10.1093/annonc/mdu360. View

15.

Judson I, Radford J, Harris M, Blay J, van Hoesel Q, Le Cesne A . Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2001; 37(7):870-7. DOI: 10.1016/s0959-8049(01)00050-8. View

16.

Zer A, Prince R, Amir E, Abdul Razak A . Evolution of Randomized Trials in Advanced/Metastatic Soft Tissue Sarcoma: End Point Selection, Surrogacy, and Quality of Reporting. J Clin Oncol. 2016; 34(13):1469-75. DOI: 10.1200/JCO.2015.64.3437. View

17.

Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez E . Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007; 357(26):2666-76. DOI: 10.1056/NEJMoa072113. View

18.

Lu E, Shatzel J, Shin F, Prasad V . What constitutes an "unmet medical need" in oncology? An empirical evaluation of author usage in the biomedical literature. Semin Oncol. 2017; 44(1):8-12. DOI: 10.1053/j.seminoncol.2017.02.009. View

19.

Van Oosterom A, Mouridsen H, Nielsen O, Dombernowsky P, Krzemieniecki K, Judson I . Results of randomised studies of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) with two different ifosfamide regimens in first- and second-line chemotherapy in advanced soft tissue sarcoma patients. Eur J Cancer. 2002; 38(18):2397-406. DOI: 10.1016/s0959-8049(02)00491-4. View

20.

Kemp R, Prasad V . Surrogate endpoints in oncology: when are they acceptable for regulatory and clinical decisions, and are they currently overused?. BMC Med. 2017; 15(1):134. PMC: 5520356. DOI: 10.1186/s12916-017-0902-9. View