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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2017

01-08-2017 | Review

Methodology of phase II clinical trials in metastatic elderly breast cancer: a literature review

Authors: B. Cabarrou, L. Mourey, F. Dalenc, L. Balardy, D. Kanoun, H. Roché, J. M. Boher, M. E. Rougé-Bugat, Thomas Filleron

Published in: Breast Cancer Research and Treatment | Issue 3/2017

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Abstract

Purpose

As the incidence of invasive breast cancer will increase with age, the number of elderly patients with a diagnosis metastatic breast cancer will also rise. But the use of cytotoxic drugs in elderly metastatic breast cancer patients is not systematic and is dreaded by medical oncologists. The need for prospective oncologic data from this population seems increasingly obvious. The main objective of this review is to investigate design and characteristics of phase II trials that assess activity and feasibility of chemotherapies in elderly advanced/metastatic breast cancer patients.

Methods

An electronic search in PUBMED allowed us to retrieve articles published in English language on phase II trials in elderly metastatic breast cancer between January 2002 and May 2016. Sixteen publications were finally included in this review.

Results

The primary endpoint was a simple, a composite, and a co-primary endpoints in 11, three, and two studies, respectively. Efficacy was the primary objective in 15 studies: simple (n = 10), composite (n = 3), co-primary endpoints (n = 2). Composite or co-primary endpoints combined efficacy and toxicity. Thirteen studies used multistage designs.

Conclusions

Only five studies evaluated the feasibility, i.e., to jointly assess efficacy and tolerance to treatment (toxicity, quality of life, etc) as primary endpoint. Development of elderly specific phase III clinical trials might be challenging, it therefore seems essential to conduct phase II clinical trials evaluating jointly efficacy and toxicity in a well-defined geriatric population. Use of multistage designs that take into account heterogeneity would allow to identify a subpopulation at interim analysis and to reduce the number of patients exposed to an inefficient or a toxic treatment regimen. It is crucial to evaluate new therapies (targeted therapies, immunotherapies) using adequate methodologies (Study design, endpoint).
Appendix
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Literature
1.
Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA (2009) Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol 27(17):2758–2765CrossRefPubMed
2.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90CrossRefPubMed
3.
DeSantis C, Ma J, Bryan L, Jemal A (2014) Breast cancer statistics, 2013. CA Cancer J Clin 64(1):52–62CrossRefPubMed
4.
Litvak DA, Arora R (2006) Treatment of elderly breast cancer patients in a community hospital setting. Arch Surg 141(10):985–990CrossRefPubMed
5.
Wildiers H et al (2007) Management of breast cancer in elderly individuals: recommendations of the International Society of Geriatric Oncology. Lancet Oncol 8(12):1101–1115CrossRefPubMed
6.
Trimble EL, Cain D, Ungerleider RS, Friedman MA, Carter CL, Freidlin B (1994) Representation of older patients in cancer treatment trials. Cancer 74(S7):2208–2214CrossRefPubMed
7.
Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS (1999) Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 341(27):2061–2067CrossRefPubMed
8.
de Glas NA et al (2014) Choosing relevant endpoints for older breast cancer patients in clinical trials: an overview of all current clinical trials on breast cancer treatment. Breast Cancer Res Treat 146(3):591–597CrossRefPubMed
9.
Wildiers H et al (2013) End points and trial design in geriatric oncology research: a joint European organisation for research and treatment of cancer–Alliance for Clinical Trials in Oncology-International Society Of Geriatric Oncology position article. J Clin Oncol 31(29):3711–3718CrossRefPubMed
10.
Mohile SG, Wildiers H (2012) A call for observational cohort studies in geriatric oncology. J Geriatr Oncol 3(3):291–293CrossRef
11.
ten Tije AJ et al (2004) Weekly paclitaxel as first-line chemotherapy for elderly patients with metastatic breast cancer. A multicentre phase II trial. Eur J Cancer 40(3):352–357CrossRefPubMed
12.
Freyer G et al (2004) Unexpected toxicities in elderly patients treated with oral idarubicin in metastatic breast cancer: the GINECO experience. Clin Oncol 16(1):17–23CrossRef
13.
Del Mastro L et al (2005) Weekly paclitaxel as first-line chemotherapy in elderly advanced breast cancer patients: a phase II study of the Gruppo Italiano di Oncologia Geriatrica (GIOGer). Ann Oncol 16(2):253–258CrossRefPubMed
14.
Gupta S et al (2005) A phase II trial of UFT and leucovorin in women 65 years and older with advanced breast cancer. Am J Clin Oncol 28(1):65–69CrossRefPubMed
15.
Bajetta E et al (2005) Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women. J Clin Oncol Off J Am Soc Clin Oncol 23(10):2155–2161CrossRef
16.
Crivellari D et al (2006) Innovative schedule of oral idarubicin in elderly patients with metastatic breast cancer: comprehensive results of a phase II multi-institutional study with pharmacokinetic drug monitoring. Ann Oncol Off J Eur Soc Med Oncol ESMO 17(5):807–812CrossRef
17.
Baweja M et al (2006) Phase II trial of oral vinorelbine for the treatment of metastatic breast cancer in patients > or = 65 years of age: an NCCTG study. Ann Oncol Off J Eur Soc Med Oncol ESMO 17(4):623–629CrossRef
18.
Kurtz JE et al (2007) Phase II trial of pegylated liposomal doxorubicin-cyclophosphamide combination as first-line chemotherapy in older metastatic breast cancer patients. Oncology 73(3–4):210–214CrossRefPubMed
19.
Basso U et al (2007) Which benefit from adding gemcitabine to vinorelbine in elderly (> or = 70 years) women with metastatic breast cancer? Early interruption of a phase II study. Ann Oncol Off J Eur Soc Med Oncol ESMO 18(1):58–63CrossRef
20.
Hess D et al (2007) Capecitabine and vinorelbine as first-line treatment in elderly patients (> or = 65 years) with metastatic breast cancer. A phase II trial (SAKK 25/99). Oncology 73(3–4):228–237CrossRefPubMed
21.
Addeo R et al (2008) Liposomal pegylated doxorubicin plus vinorelbine combination as first-line chemotherapy for metastatic breast cancer in elderly women > or = 65 years of age. Cancer Chemother Pharmacol 62(2):285–292CrossRefPubMed
22.
Mlineritsch B et al (2009) Multicenter phase II study of pegylated liposomal doxorubicin in combination with vinorelbine as first-line treatment in elderly patients with metastatic breast cancer. Onkologie 32(1–2):18–24PubMed
23.
Wang H-Q et al (2010) Capecitabine combined with weekly docetaxel in Chinese patients > 65 years with anthracycline-resistant metastatic breast cancer. Chin Med J (Engl) 123(22):3212–3216
24.
Addeo R et al (2010) Low-dose metronomic oral administration of vinorelbine in the first-line treatment of elderly patients with metastatic breast cancer. Clin Breast Cancer 10(4):301–306CrossRefPubMed
25.
Dong N, Wang M, Li H, Cui Y, Guo Q (2012) Gemcitabine in combination with vinorelbine in elderly patients with anthracycline- and taxane-pretreated metastatic breast cancer. Cancer Chemother Pharmacol 69(5):1315–1322CrossRefPubMed
26.
Falandry C et al (2013) Impact of geriatric risk factors on pegylated liposomal doxorubicin tolerance and efficacy in elderly metastatic breast cancer patients: final results of the DOGMES multicentre GINECO trial. Eur J Cancer Oxf Engl 49(13):2806–2814CrossRef
27.
Simon R (1999) Bayesian design and analysis of active control clinical trials. Biometrics 55(2):484–487CrossRefPubMed
28.
Katz S (1983) Assessing self-maintenance: activities of daily living, mobility, and instrumental activities of daily living. J Am Geriatr Soc 31(12):721–727CrossRefPubMed
29.
Zanocchi M et al (2004) L’indice medico di non autosufficienza: validazione e comparazione con le scale AFL e IADL. Minerva Med 95(2):143–151PubMed
30.
Le Saux O, Falandry C, Gan HK, You B, Freyer G, Péron J (2016) Inclusion of elderly patients in oncology clinical trials. Ann Oncol 27:1799–1804CrossRefPubMed
31.
Talarico L, Chen G, Pazdur R (2004) Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration. J Clin Oncol 22(22):4626–4631CrossRefPubMed
32.
Balducci L, Extermann M (2000) Management of cancer in the older person: a practical approach. Oncologist 5(3):224–237CrossRefPubMed
33.
Debled M, Bellera C, Donamaria C, Soubeyran P (2011) Chemotherapy treatment for older women with metastatic breast cancer: what is the evidence? Cancer Treat Rev 37(8):590–598CrossRefPubMed
34.
Freyer G et al (2006) Dealing with metastatic breast cancer in elderly women: results from a French study on a large cohort carried out by the ‘Observatory on Elderly Patients’. Ann Oncol 17(2):211–216CrossRefPubMed
35.
D’hondt R et al (2004) Safety and efficacy of weekly docetaxel in frail and/or elderly patients with metastatic breast cancer: a phase II study. Anticancer Drugs 15(4):341–346CrossRefPubMed
36.
Beuselinck B, Wildiers H, Wynendaele W, Dirix L, Kains J-P, Paridaens R (2010) Weekly paclitaxel versus weekly docetaxel in elderly or frail patients with metastatic breast carcinoma: a randomized phase-II study of the Belgian Society of Medical Oncology. Crit Rev Oncol Hematol 75(1):70–77CrossRefPubMed
37.
Biganzoli L et al (2012) Management of elderly patients with breast cancer: updated recommendations of the International Society of Geriatric Oncology (SIOG) and European Society of Breast Cancer Specialists (EUSOMA). Lancet Oncol 13(4):e148–e160CrossRefPubMed
38.
Rousseau F et al (2010) Impact of an all-oral capecitabine and vinorelbine combination regimen on functional status of elderly patients with advanced solid tumours: a multicentre pilot study of the French geriatric oncology group (GERICO). Crit Rev Oncol Hematol 76(1):71–78CrossRefPubMed
39.
Fleming TR (1982) One-sample multiple testing procedure for phase II clinical trials. Biometrics 38:143–151CrossRefPubMed
40.
Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10(1):1–10CrossRefPubMed
41.
Bryant J, Day R (1995) Incorporating toxicity considerations into the design of two-stage phase II clinical trials. Biometrics 51:1372–1383CrossRefPubMed
42.
Zee B, Melnychuk D, Dancey J, Eisenhauer E (1999) Multinomial phase II cancer trials incorporating response and early progression. J Biopharm Stat 9(2):351–363CrossRefPubMed
43.
Chang MN, Devidas M, Anderson J (2007) One-and two-stage designs for phase II window studies. Stat Med 26(13):2604–2614CrossRefPubMed
44.
Pusztai L, Anderson K, Hess KR (2007) Pharmacogenomic predictor discovery in phase II clinical trials for breast cancer. Clin Cancer Res 13(20):6080–6086CrossRefPubMed
45.
Jones CL, Holmgren E (2007) An adaptive Simon two-stage design for phase 2 studies of targeted therapies. Contemp Clin Trials 28(5):654–661CrossRefPubMed
46.
Tournoux-Facon C, De Rycke Y, Tubert-Bitter P (2011) How a new stratified adaptive phase II design could improve targeting population. Stat Med 30(13):1555–1562CrossRefPubMed
47.
48.
Repetto L et al (2002) Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study. J Clin Oncol 20(2):494–502CrossRefPubMed
49.
Easterbrook PJ, Gopalan R, Berlin JA, Matthews DR (1991) Publication bias in clinical research. Lancet 337(8746):867–872CrossRefPubMed
50.
van Lent M, Overbeke J, Out HJ (2014) Role of editorial and peer review processes in publication bias: analysis of drug trials submitted to eight medical journals. PLoS ONE 9(8):e104846CrossRefPubMedPubMedCentral
51.
Christman K, Muss HB, Case LD, Stanley V (1992) Chemotherapy of metastatic breast cancer in the elderly: the Piedmont Oncology Association experience. JAMA 268(1):57–62CrossRefPubMed
Metadata
Title
Methodology of phase II clinical trials in metastatic elderly breast cancer: a literature review
Authors
B. Cabarrou
L. Mourey
F. Dalenc
L. Balardy
D. Kanoun
H. Roché
J. M. Boher
M. E. Rougé-Bugat
Thomas Filleron
Publication date
01-08-2017
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4278-5

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