Impact of early palliative care on overall survival of patients with metastatic upper gastrointestinal cancers treated with first-line chemotherapy: a randomised phase III trial

Emilie Hutt, Arlette Da Silva, Emilie Bogart, Sara Le Lay-Diomande, Diane Pannier, Stéphanie Delaine-Clisant, Marie-Cécile Le Deley, Antoine Adenis, Emilie Hutt, Arlette Da Silva, Emilie Bogart, Sara Le Lay-Diomande, Diane Pannier, Stéphanie Delaine-Clisant, Marie-Cécile Le Deley, Antoine Adenis

Abstract

Introduction: Palliative care (PC) has usually been offered at the end-of-life stage, although the WHO recommends providing PC as early as possible in the course of the disease. A recent study has shown that early PC (EPC) provides a more meaningful effect on quality of life and, surprisingly, on overall survival (OS) than standard treatment for patients with metastatic lung cancer. Whether EPC benefits also apply to patients with metastatic upper gastrointestinal (GI) cancers is unknown.

Methods and analysis: EPIC is a randomised phase III trial comparing EPC plus standard oncologic care versus standard oncologic care in patients with metastatic upper GI cancers. Its primary objective is to evaluate the efficacy of EPC in terms of OS. Its secondary objectives are to assess the effects of EPC on patient-reported outcomes (quality of life, depression and anxiety) and the effect of EPC on the number of patients receiving chemotherapy in their last 30 days of life. Assuming an exponential distribution of survival time, 381 deaths are required to ensure an 80% power for an absolute difference of 10% in 1 year OS rates (40% vs 50.3%, HR=0.75; log rank test two-sided alpha=5%), leading to a planned sample size of 480 patients enrolled over 3 years and a final analysis at 4 years. The main analysis will be performed on the intent-to-treat dataset.

Ethics and dissemination: This study was approved by the 'Comité de Protection des Personnes Nord-Ouest I' (4 April 2016), complies with the Helsinki declaration and French laws and regulations and follows the International Conference on Harmonisation E6 (R1) Guideline for Good Clinical Practice. The trial results, even if they are inconclusive, will be presented at international oncology congresses and published in peer-reviewed journals.

Trial registration numbers: EudraCT: 2015-A01943-46; Pre-results. NCT02853474.

Keywords: gastrointestinal cancer; palliative care; randomized trial.

Conflict of interest statement

Competing interests: None declared.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
Study design.

References

    1. SFAP. accessed 6 Jan 2017
    1. Bakitas MA, Tosteson TD, Li Z, et al. . Early versus delayed initiation of concurrent palliative oncology care: patient outcomes in the ENABLE III randomized controlled trial. J Clin Oncol 2015;33:1438–45. 10.1200/JCO.2014.58.6362
    1. . accessed 6 Jan 2017.
    1. Loi n°99-447 Du 9 juin 1999 visant à garantir le droit à l’accès aux soins palliatifs. JORF n° 132 du 10 juin 1999.
    1. Temel JS, Greer JA, Muzikansky A, et al. . Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010;363:733–42. 10.1056/NEJMoa1000678
    1. Clinical practice guidelines for quality palliative care. 2nd ed Pittsburgh: National Consensus Project, 2009. (accessed 23Jul 2010).
    1. Pirl WF, Greer JA, Traeger L, et al. . Depression and survival in metastatic non-small-cell lung cancer: effects of early palliative care. J Clin Oncol 2012;30:1310–5. 10.1200/JCO.2011.38.3166
    1. Schnipper LE, Smith TJ, Raghavan D, et al. . American Society of clinical oncology identifies five key opportunities to improve care and reduce costs: the top five list for oncology. J Clin Oncol 2012;30:1715–24. 10.1200/JCO.2012.42.8375
    1. Conroy T, Desseigne F, Ychou M, et al. . FOLFIRINOX improves survival in patients with metastatic pancreatic Cancer. N Engl J Med 2011;364:1817–25.
    1. Lordick F, Kang YK, Chung HC, et al. . Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol 2013;14:490–9. 10.1016/S1470-2045(13)70102-5
    1. Malka D, Cervera P, Foulon S, et al. . Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO): a randomised, open-label, non-comparative phase 2 trial. Lancet Oncol 2014;15:819–28. 10.1016/S1470-2045(14)70212-8
    1. Ducreux M, Sa Cuhna A, Caramella C, et al. . Cancer of the pancreas: esmo Clinical Practice guidelines. Ann Oncol 2015;26(suppl 5):v56–v68.
    1. Valle JW, Borbath I, Khan SA, et al. . Biliary cancer: esmo clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016;27(suppl 5):v28–v37. 10.1093/annonc/mdw324
    1. Smyth EC, Verheij M, Allum W, et al. . Gastric Cancer: esmo clinical Practice guidelines. Ann Oncol 2016;27(suppl 5):v38–v49.
    1. Oken MM, Creech RH, Tormey DC, et al. . Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649–56. 10.1097/00000421-198212000-00014
    1. Lan KKG, DeMets DL. Discrete Sequential Boundaries for clinical trials. Biometrika 1983;70:659–63. 10.2307/2336502
    1. O’Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics 1979;35:549–56. 10.2307/2530245
    1. Royston P, Parmar MK. The use of restricted mean survival time to estimate the treatment effect in randomized clinical trials when the proportional hazards assumption is in doubt. Stat Med 2011;30:2409–21. 10.1002/sim.4274
    1. World medical association. (accessed 6 Jan 2017).
    1. ICH. (accessed 6 Jan 2017).

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner