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CHALLENGES AND METHODOLOGIES IN USING PROGRESSION FREE SURVIVAL AS A SURROGATE FOR OVERALL SURVIVAL IN ONCOLOGY

Part of: Special Collection - Methods

Published online by Cambridge University Press:  10 July 2018

Karla Hernandez-Villafuerte ,
Alastair Fischer  and
Nicholas Latimer
Karla Hernandez-Villafuerte
Affiliation:
German Cancer Research Center (DKFZ)[email protected]
Alastair Fischer
Affiliation:
Office of Health Economics
Nicholas Latimer
Affiliation:
ScHARR, University of Sheffield
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Abstract

Objectives:

A primary outcome in oncology trials is overall survival (OS). However, to estimate OS accurately requires a sufficient number of patients to have died, which may take a long time. If an alternative end point is sufficiently highly correlated with OS, it can be used as a surrogate. Progression-free survival (PFS) is the surrogate most often used in oncology, but does not always satisfy the correlation conditions for surrogacy. We analyze the methodologies used when extrapolating from PFS to OS.

Methods:

Davis et al. previously reviewed the use of surrogate end points in oncology, using papers published between 2001 and 2011. We extend this, reviewing papers published between 2012 and 2016. We also examine the reporting of statistical methods to assess the strength of surrogacy.

Results:

The findings from 2012 to 2016 do not differ substantially from those of 2001 to 2011: the same factors are shown to affect the relationship between PFS and OS. The proportion of papers reporting individual patient data (IPD), strongly recommended for full assessment of surrogacy, remains low: 33 percent. A wide range of methods has been used to determine the appropriateness of surrogates. While usually adhering to reporting standards, the standard of scholarship appears sometimes to be questionable and the reporting of results often haphazard.

Conclusions:

Standards of analysis and reporting PFS to OS surrogate studies should be improved by increasing the rigor of statistical reporting and by agreeing to a minimum set of reporting guidelines. Moreover, the use of IPD to assess surrogacy should increase.

Keywords

CancerSurrogate end pointsOverall survival (OS)Progression-free survival (PFS)Postprogression survival (PPS)
Type
Method
Information
International Journal of Technology Assessment in Health Care , Volume 34 , Issue 3 , 2018 , pp. 300 - 316
Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

Funding: The Pharmaceutical Oncology Initiative (POI) of the Association of the British Pharmaceutical Industry (ABPI) commissioned the Office of Health Economics (OHE) in April 2016 to undertake a landscape study on methods and approaches to extrapolation from clinical endpoints measured in trials involving overall survival. We gratefully acknowledge the contributions of Francesco Pignatti (EMA), Eli Gavraj and Ian Watson (NICE), Prof Andrew Stevens (Chair of a NICE Appraisal Committee), Oriana Ciani and Prof Rod Taylor (University of Exeter Medical School), and POI member organizations. Nevertheless, views expressed in this paper are those of the authors and are not necessarily those of POI, EMA, NICE or the University of Exeter. Karla Hernandez-Villafuerte's previous affiliation was Office of Health Economics. Southside, 7th Floor, 105 Victoria Street, London SW1E 6QT.

References

REFERENCES

1.Davis, S, Tappenden, P, Cantrell, A. A review of studies examining the relationship between progression-free survival and overall survival in advanced or metastatic cancer. London: National Institute for Health and Care Excellence (NICE), 2012.Google Scholar
2.Latimer, NR. Survival analysis for economic evaluations alongside clinical trials: Extrapolation with patient-level data. Med Decis Making. 2013;33:743-754.Google Scholar
3.Latimer, NR, Abrams, KR, Lambert, PC, et al. Adjusting survival time estimates to account for treatment switching in randomized controlled trials: An economic evaluation context. Med Decis Making. 2014;34:387-402.Google Scholar
4.Ciani, O, Davis, S, Tappenden, P, et al. Validation of surrogate endpoints in advanced solid tumors: Systematic review of statistical methods, results, and implications for policy makers. Int J Technol Assess Health Care. 2014;30:312-324.Google Scholar
5.Imai, H, Mori, K, Ono, A, et al. Individual-level data on the relationships of progression-free survival and post-progression survival with overall survival in patients with advanced non-squamous non-small cell lung cancer patients who received second-line chemotherapy. Med Oncol. 2014;31:1-7.Google Scholar
6.Imai, H, Mori, K, Wakuda, K, et al. Progression-free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer. Ann Thorac Med. 2015;10:61-66.Google Scholar
7.Kasahara, N, Imai, H, Kaira, K, et al. Clinical impact of post-progression survival on overall survival in patients with limited-stage disease small cell lung cancer after first-line chemoradiotherapy. Radiol Oncol. 2015;49:409-415.Google Scholar
8.Yoshino, R, Imai, H, Mori, K, et al. Surrogate endpoints for overall survival in advanced non-small-cell lung cancer patients with mutations of the epidermal growth factor receptor gene. Mol Clin Oncol. 2014;2:731-736.Google Scholar
9.Yoshino, R, Imai, H, Mori, K, et al. Clinical impact of postprogression survival for overall survival in elderly patients (aged 75 years or older) with advanced nonsmall cell lung cancer. J Cancer Res Ther. 2015;11:606.Google Scholar
10.Shitara, K, Matsuo, K, Muro, K, Doi, T, Ohtsu, A. Progression-free survival and post-progression survival in patients with advanced gastric cancer treated with first-line chemotherapy. J Cancer Res Clin Oncol. 2013;139:1383138-9.Google Scholar
11.Aboshi, M, Kaneko, M, Narukawa, M. Factors affecting the association between overall survival and progression-free survival in clinical trials of first-line treatment for patients with advanced non-small cell lung cancer. J Cancer Res Clin Oncol. 2014;140:839-848.Google Scholar
12.Bria, E, Massari, F, Maines, F, et al. Progression-free survival as primary endpoint in randomized clinical trials of targeted agents for advanced renal cell carcinoma: Correlation with overall survival, benchmarking and power analysis. Crit Rev Oncol Hematol. 2015;93:50-59.Google Scholar
13.Delea, TE, Khuu, A, Heng, DY, Haas, T, Soulieres, D. Association between treatment effects on disease progression end points and overall survival in clinical studies of patients with metastatic renal cell carcinoma. Br J Cancer. 2012;107:1059-1068.Google Scholar
14.Li, X, Liu, S, Gu, H, Wang, D. Surrogate end points for survival in the target treatment of advanced non-small-cell lung cancer with gefitinib or erlotinib. J Cancer Res Clin Oncol. 2012;138:1963-1969.Google Scholar
15.Shitara, K, Ikeda, J, Yokota, T, et al. Progression-free survival and time to progression as surrogate markers of overall survival in patients with advanced gastric cancer: Analysis of 36 randomized trials. Invest New Drugs. 2012;30:1224-1231.Google Scholar
16.Félix, J, Aragão, F, Almeida, JM, et al. Time-dependent endpoints as predictors of overall survival in multiple myeloma. BMC Cancer. 2013;13:1-12.Google Scholar
17.Giessen, C, Laubender, RP, Ankerst, DP, et al. Progression-free survival as a surrogate endpoint for median overall survival in metastatic colorectal cancer: Literature-based analysis from 50 randomized first-line trials. Clin Cancer Res. 2013;19:225-235.Google Scholar
18.Han, K, Ren, M, Wick, W, et al. Progression-free survival as a surrogate endpoint for overall survival in glioblastoma: A literature-based meta-analysis from 91 trials. Neuro Oncol. 2013;16:696-706.Google Scholar
19.Petrelli, F, Barni, S. Correlation of progression-free and post-progression survival with overall survival in advanced colorectal cancer. Ann Oncol. 2013;24:186-192.Google Scholar
20.Petrelli, F, Barni, S. Is overall survival still the primary endpoint in maintenance non-small cell lung cancer studies? An analysis of phase III randomised trials. Transl Lung Cancer Res. 2013;2:6-13.Google Scholar
21.Sidhu, R, Rong, A, Dahlberg, S. Evaluation of progression-free survival as a surrogate endpoint for survival in chemotherapy and targeted agent metastatic colorectal cancer trials. Clin Cancer Res. 2013;19:969-976.Google Scholar
22.Beauchemin, C, Cooper, D, Lapierre, M-È, Yelle, L, Lachaine, J. Progression-free survival as a potential surrogate for overall survival in metastatic breast cancer. Onco Targets Ther. 2014;7:1101-10.Google Scholar
23.Flaherty, KT, Hennig, M, Lee, SJ, et al. Surrogate endpoints for overall survival in metastatic melanoma: A meta-analysis of randomised controlled trials. Lancet Oncol. 2014;15:297-304.Google Scholar
24.Singh, S, Wang, X, Law, C. Association between time to disease progression end points and overall survival in patients with neuroendocrine tumors. Gastrointest Cancer. 2014;4:103-113.Google Scholar
25.Cartier, S, Zhang, B, Rosen, VM, et al. Relationship between treatment effects on progression-free survival and overall survival in multiple myeloma: A systematic review and meta-analysis of published clinical trial data. Oncol Res Treat. 2015;38:88-94.Google Scholar
26.Chen, Y-P, Sun, Y, Chen, L, et al. Surrogate endpoints for overall survival in combined chemotherapy and radiotherapy trials in nasopharyngeal carcinoma: Meta-analysis of randomised controlled trials. Radiother Oncol. 2015;116:157-166.Google Scholar
27.Giessen, C, Laubender, RP, Ankerst, DP, et al. Surrogate endpoints in second-line treatment for mCRC: A systematic literature-based analysis from 23 randomised trials. Acta Oncol. 2015;54:187-193.Google Scholar
28.Petrelli, F, Coinu, A, Borgonovo, K, Cabiddu, M, Barni, S. Progression-free survival as surrogate endpoint in advanced pancreatic cancer: Meta-analysis of 30 randomized first-line trials. Hepatobiliary Pancreat Dis Int. 2015;14:124-131.Google Scholar
29.Amir, E, Seruga, B, Kwong, R, Tannock, IF, Ocaña, A. Poor correlation between progression-free and overall survival in modern clinical trials: Are composite endpoints the answer? Eur J Cancer. 2012;48:385-388.Google Scholar
30.Hotta, K, Suzuki, E, Di Maio, M, et al. Progression-free survival and overall survival in phase III trials of molecular-targeted agents in advanced non-small-cell lung cancer. Lung Cancer. 2013;79:20-26.Google Scholar
31.Kawakami, H, Okamoto, I, Hayashi, H, et al. Postprogression survival for first-line chemotherapy in patients with advanced gastric cancer. Eur J Cancer. 2013;49:3003-3009.Google Scholar
32.Petrelli, F, Barni, S. Surrogate endpoints in metastatic breast cancer treated with targeted therapies: An analysis of the first-line phase III trials. Med Oncol. 2014;31:1-8.Google Scholar
33.Adunlin, G, Cyrus, JWW, Dranitsaris, G. Correlation between progression-free survival and overall survival in metastatic breast cancer patients receiving anthracyclines, taxanes, or targeted therapies: A trial-level meta-analysis. Breast Cancer Res Treat. 2015;154:591-608.Google Scholar
34.Hotta, K, Kato, Y, Leighl, N, et al. Magnitude of the benefit of progression-free survival as a potential surrogate marker in phase 3 trials assessing targeted agents in molecularly selected patients with advanced non-small cell lung cancer: Systematic review. PLoS One. 2015;10:e0121211.Google Scholar
35.Johnson, KR, Liauw, W, Lassere, MND. Evaluating surrogacy metrics and investigating approval decisions of progression-free survival (PFS) in metastatic renal cell cancer: A systematic review. Ann Oncol. 2015;26:485-496.Google Scholar
36.Özer-Stillman, I, Strand, L, Chang, J, Mohamed, AF, Tranbarger-Freier, KE. Meta-analysis for the association between overall survival and progression-free survival in gastrointestinal stromal tumor. Clin Cancer Res. 2015;21:295-302.Google Scholar
37.Suzuki, H, Hirashima, T, Okamoto, N, et al. Relationship between progression-free survival and overall survival in patients with advanced non-small cell lung cancer treated with anticancer agents after first-line treatment failure. Asia Pac J Clin Oncol. 2015;11:121-128.Google Scholar
38.Moriwaki, T, Yamamoto, Y, Gosho, M, et al. Correlations of survival with progression-free survival, response rate, and disease control rate in advanced biliary tract cancer: A meta-analysis of randomised trials of first-line chemotherapy. Br J Cancer. 2016;114:881-888.Google Scholar
39.Petrelli, F, Barni, S. Surrogate end points and postprogression survival in renal cell carcinoma: An analysis of first-line trials with targeted therapies. Clin Genitourin Cancer. 2013;11:385-389.Google Scholar
40.Shitara, K, Matsuo, K, Muro, K, Doi, T, Ohtsu, A. Correlation between overall survival and other endpoints in clinical trials of second-line chemotherapy for patients with advanced gastric cancer. Gastric Cancer. 2014;17:362-370.Google Scholar
41.Ciani, O, Buyse, M, Garside, R, Peters, J, Saad, ED, Stein, K, et al. Meta-analyses of randomized controlled trials show suboptimal validity of surrogate outcomes for overall survival in advanced colorectal cancer. J Clin Epidemiol. 2015;68:833-842.Google Scholar
42.Terashima, T, Yamashita, T, Takata, N, et al. Post-progression survival and progression-free survival in patients with advanced hepatocellular carcinoma treated by sorafenib. Hepatol Res. 2015;46:650-656.Google Scholar
43.Galsky, MD, Krege, S, Lin, CC, et al. Relationship between 6-and 9-month progression-free survival and overall survival in patients with metastatic urothelial cancer treated with first-line cisplatin-based chemotherapy. Cancer. 2013;119:3020-3026.Google Scholar
44.Halabi, S, Rini, B, Escudier, B, Stadler, WM, Small, EJ. Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic renal cell carcinoma. Cancer. 2014;120:52-60.Google Scholar
45.Négrier, S, Bushmakin, AG, Cappelleri, JC, et al. Assessment of progression-free survival as a surrogate end-point for overall survival in patients with metastatic renal cell carcinoma. Eur J Cancer. 2014;50:1766-1771.Google Scholar
46.Laporte, S, Squifflet, P, Baroux, N, et al. Prediction of survival benefits from progression-free survival benefits in advanced non-small-cell lung cancer: Evidence from a meta-analysis of 2334 patients from 5 randomised trials. BMJ Open. 2013;3:e001802.Google Scholar
47.Mauguen, A, Pignon, J-P, Burdett, S, et al. Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: A re-analysis of meta-analyses of individual patients' data. Lancet Oncol. 2013;14:619-26.Google Scholar
48.Agarwal, N, Bellmunt, J, Maughan, BL, et al. Six-month progression-free survival as the primary endpoint to evaluate the activity of new agents as second-line therapy for advanced urothelial carcinoma. Clin Genitourin Cancer. 2014;12:130-137.Google Scholar
49.Foster, NR, Renfro, LA, Schild, SE, et al. Multitrial evaluation of progression-free survival as a surrogate end point for overall survival in first-line extensive-stage small-cell lung cancer. J Thorac Oncol. 2015;10:1099-1106.Google Scholar
50.Shi, Q, De Gramont, A, Grothey, A, et al. Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials: Findings from the analysis and research in cancers of the digestive system database. J Clin Oncol. 2015;33:22-28.Google Scholar
51.Paoletti, X, Oba, K, Bang, Y-J, et al. Progression-free survival as a surrogate for overall survival in advanced/recurrent gastric cancer trials: A meta-analysis. J Natl Cancer Inst. 2013;105:1667-70.Google Scholar
52.Michiels, S, Pugliano, L, Marguet, S, et al. Progression-free survival as surrogate endpoint for overall survival in clinical trials of HER2-targeted agents in HER2-positive metastatic breast cancer. Ann Oncol. 2016;27:1029-1034.Google Scholar
53.IQWiG. Validity of surrogate endpoints in oncology: Executive summary of rapid rep–rt A10-05, Version 1.1. Institute for Quality and Efficiency in Health Care: Executive Summaries. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2005.Google Scholar
54.Lencioni, R, Llovet, JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52-60.Google Scholar
55.Burzykowski, T, Buyse, M, Piccart-Gebhart, MJ, et al. Evaluation of tumor response, disease control, progression-free survival, and time to progression as potential surrogate end points in metastatic breast cancer. J Clin Oncol. 2008;26:1987-1992.Google Scholar
56.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;91:713-725.Google Scholar
57.Prentice, RL. Surrogate endpoints in clinical trials: Definition and operational criteria. Stat Med. 1989;8:431-440.Google Scholar
58.Ciani, O, Buyse, M, Drummond, M, et al. Use of surrogate end points in healthcare policy: A proposal for adoption of a validation framework. Nat Rev Drug Discov. 2016;15:516.Google Scholar
59.Buyse, M, Molenberghs, G, Burzykowski, T, Renard, D, Geys, H. The validation of surrogate endpoints in meta-analyses of randomized experiments. Biostatistics. 2000;1:49-67.Google Scholar
60.Stevens, W, Philipson, T, Wu, Y, Chen, C, Lakdawalla, D. A cost-benefit analysis of using evidence of effectiveness in terms of progression free survival in making reimbursement decisions on new cancer therapies. Forum Health Econ Policy. 2014;17:21-52.Google Scholar
61.Saad, ED, Katz, A. Progression-free survival and time to progression as primary end points in advanced breast cancer: Often used, sometimes loosely defined. Ann Oncol. 2008;20:460-464.Google Scholar
62.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;15:134.Google Scholar