25/11/15
L’Ormonoterapia:
Compliance e Controlli
Ornella Garrone
A.O. S. Croce e Carle Cuneo
25/11/15
B ackground
• About 70-75% of BC are HR +
• The treatment of choice considers TAM or AI depending on menopausal status
• Both drugs are responsible of “class specific AE”
• Prolongation of therapy in selected cases might worsen AE
• Doctors should be aware of them
25/11/15
Quality indicators : appropriate hormonotherapy (EUS OMA-
S ENONETWORK)
• The proportion of patients with endocrine sensitive invasive carcinoma who received hormonotherapy, out the the total number of patients with this diagnosis
– Minimum standard: 80%
– Target >90%
Rosselli Del Turco M. et al. EJC 2010
Mano MP Senonetwork 2013
25/11/15
Pers is tence-Adherence
• Persistence: continuous use of adjuvant hormonal therapy, with few gaps in treatments or in prescription refills
• Adherence: degree of conformity to the prescribed dosage and daily frequency of the treatment
Osterberg I, et al. NEJM 2005;487-97
25/11/15
Rate of failure in
pers is tence/compliance
• Rates of nonpersistence (early discontinuation of medication) in women who start adjuvant endocrine therapy range from 20% to 50%
• Rates of compliance (conformity to prescribed dosing) average 74% to 84%, and may diminish over time Burstein HJ JCO
2014
25/11/15
Compliance to AI according to country and educational
approach
Neven P. et al. The Breast 2014
25/11/15
Pers is tence to AI according to country and educational
approach
Neven P. et al. The Breast 2014
25/11/15
Tamoxifen-related AE
• Hot Flashes, sweats
• Thromboembolism
•
Endometrial
Endometrial cancerCancer
25/11/15
Endometrial Health
• Endometrial cancer ≈ 0.5% in TAM treated patients
• Regular gynecologic follow-up is recommended for all women
• Patients who receive TAM therapy are at increased risk for developing endometrial cancer and should be advised to report any vaginal bleeding to their physicians
25/11/15
F-UP Linee guida AIOM 2014
F-UP Linee guida NCCN 2015
25/11/15
Aromatas e Inhibitors
• Muscoloskeletal events
• Bone health
• Vasomotor symptoms
• Lipid metabolisms and cardiovascular toxicity
Mus colos keletal
events
25/11/15
Muscoloskeletal toxicity
• Adversely affect adherence and cause premature treatment discontinuation in 15- 22% of patients
• Risk factors:
– Previous taxane-based CT
– High baseline pain score
– Young age Lintermans A et al. BCRT 2014; Henry NL et al.
JCO 2012
25/11/15
• dose di carico: 300.000 UI di colecalciferolo (DIBASE) x 2 giorni consecutivi per os
• mantenimento: 100.000 UI (1 fiala al mese) per os
Vitamina D:
dosaggio
Bertoldo, Ripamonti, Del Mastro Therapy perspectives 2010
25/11/15
Aromatas e Inhibitors
• Muscoloskeletal events
• Bone health
• Vasomotor symptoms
• Lipid metabolisms and cardiovascular toxicity
B one
Health
25/11/15 Hirbe A Clin Cancer Res 2006;12:6309s- 6314s
CANCER TREATMENT INDUCED
B ONE LOS S
25/11/15 Hirbe A Clin Cancer Res 2006;12:6309s-6314s
B one is an Endocrine Organ
25/11/15
B one Health
• By inducing a hypo-estrogenic state, AI cause accelerated bone loss and reduced mineral density (BMD)greater odds of bone fractures (Chien AJ et al. J Clin Oncol 2006; Geisler J et al. J Clin Oncol 2002)
– Major cause of morbidity and excess of mortality in pre and postmenopausal women
(Pagani O et al. NEJM 2014; Johnell O et al. Osteoporos Int 2005)
• Upon cessation of AI therapy the adverse effect on bone health partially reverse and disappeared (Forbes JF et al. Lancet Oncol 2008; Coleman RE et al.
Breast Cancer Res Treat 2010)
25/11/15
B one Health
• Identification of women with prior bone morbidity (Kwan ML et al. PLoS One 2014)
• BMD measurements by dual-energy-X-ray absorpiometry is recommended in all patients before starting AI therapy (Gralow JR et al. J Natl Compr Canc Netw 2013)
• Calcium and vitamin D supplementation
(Coleman R et al. Ann Oncol 2014)
• Bisphosphonates
• Lifestyle modifications
25/11/15
Calcium and vitamin D s upplementation
• Loading dose: 300.000 IU p.o. for 2 days consecutively (Colecalcipherol)
• Maintenance: 100.000 IU p.o. monthly
• Calcium supplementation: 1000 mg/d
25/11/15
F-up Linee guida AIOM 2014
25/11/15
F-up Linee guida NCCN 2015
25/11/15
ES MO Guidelines : bone health
Coleman R et al. Ann Oncol 2014
25/11/15
The new nota 79
25/11/15
Aromatas e Inhibitors
• Muscoloskeletal events Bone health
• Vasomotor symptoms
• Lipid metabolisms and cardiovascular toxicity
Lipid metabolis m and cardiovas cular
toxicity
25/11/15
Lipid metabolis m
• Data from clinical trials showed that increases in lipid parameters seem to be associated, or at least partly, with TAM withdrawal rather than a direct effect of AI use
• Only minor effects on plasma lipid levels have been noted for all AIs compared to placebo
• Patients should be monitored before and during AI therapy (particularly those with prior TAM exposure) Lintermans A et al. Expert Opin on Drug Safety
2015
25/11/15
F-up Linee guida AIOM 2014
25/11/15
Conclus ions (1)
• For TAM users: regular gynecologic follow- up
– Minimum standard: 80%
– Target >90%
• For IA users: Lipid and cardiovascular health should be monitored before and during therapy (annually)
– Minimum standard: 80%
– Target >90%
25/11/15
Conclus ions (2)
• For IA users: Bone health should be monitored before and during therapy (calcium and vitamin D supplementation and BMD at baseline and then after 18-24 months, bisphosphonates)
– Minimum standard: 80%
– Target >90%
• For all Clinicians: please listen to your patients
25/11/15
Conclus ions (3)
• The importance of patient compliance with adjuvant AI treatment is clear, in terms of treatment outcome
• Improved patient physician interaction would be beneficial
• Adherence with medication is influenced both by patients’ beliefs in the necessity of treatment and by their concerns about medication
