CONGRESSO NAZIONALE AIOM GIOVANI
SESSIONE: “PREMIAZIONE MIGLIORI TRE LAVORI GIOVANI”
Dr. Matteo Lambertini
U.O. Oncologia Medica 2
IRCCS AOU San Martino – IST, Genova
SOPPRESSIONE OVARICA CON LHRH ANALOGHI DURANTE CHEMIOTERAPIA PER LA PRESERVAZIONE DELLA FUNZIONE OVARICA E DELLA FERTILITÀ NELLE PAZIENTI CON CARCINOMA
MAMMARIO: METANALISI DI STUDI RANDOMIZZATI
8 luglio 2016 Perugia
Disclosure Information
Relationship Relevant to this Session
Lambertini, Matteo:
No relevant relationship to disclose.
Study Background
• Ovarian function loss and impaired fertility are possible
consequences of anticancer treatments and have a negative impact on global health of young breast cancer survivors1.
• Embryo and oocyte cryopreservation are the standard
procedure for fertility preservation2,3. No proven methods for preservation of ovarian function are yet available.
• According to the 2013 ASCO and ESMO guidelines, temporary ovarian suppression with LHRHa during
chemotherapy is still considered an experimental strategy to preserve ovarian function and fertility2,3.
1. Poggio F et al, Expert Rev QoL Cancer Care 2016; 1:5-7. 2. Loren AW et al, J Clin Oncol 2013; 31(19):2500-10. 3. Peccatori FA et al, Ann Oncol
Study Background
Important News in 2015
Study Background
Lambertini M et al, Ann Oncol 2015; 26(12):2408-19
Study Design
• Quantitative synthesis of randomized trials aiming to evaluate the efficacy and safety of temporary ovarian suppression with LHRHa during chemotherapy as a
strategy to preserve ovarian function and fertility in young breast cancer patients.
• The work was done and reported according to the PRISMA guidelines for reporting of systematic reviews.
• A literature search using PubMed, Embase and the
Cochrane Library was performed with no date restriction up to April 30th, 2015; abstracts presented at ASCO, ASCO breast, SABCS and ESMO meetings were also searched.
Eligibility Criteria
• Inclusion criteria:
a) randomized trials designed to evaluate the efficacy of the addition of LHRHa to chemotherapy in terms of POF and/or fertility after chemotherapy;
b) studies conducted in early-stage premenopausal breast cancer patients who were candidates for neo-adjuvant and/or adjuvant chemotherapy;
c) the odds ratio (OR) for POF and/or pregnancies had to be reported or could be computed from the data presented in the selected studies.
• Exclusion criteria:
a) randomized trials designed to evaluate the efficacy of the addition of LHRHa to chemotherapy in terms of POF and/or fertility after chemotherapy in patients with autoimmune disease or tumors other than breast cancer;
b) non-randomized studies conducted to evaluate the role of LHRHa during chemotherapy as a strategy to preserve ovarian function and/or fertility;
c) ongoing studies which had not yet been presented or published at the time of the literature search.
Study Objectives and Endpoints
• Primary objective: to compare the incidence of treatment- related POF between patients treated with concurrent
temporary ovarian suppression with LHRHa during
chemotherapy and those who received chemotherapy alone.
• Secondary objectives:
a) to compare the incidence of treatment-related amenorrhea 1 year after the end of chemotherapy;
b) to compare pregnancy rates;
c) to evaluate the impact of concurrent administration of LHRHa and chemotherapy on disease-free survival (DFS).
Statistical Considerations
• Fixed effect model was estimated with the Mantel-Haenszel method for OR and the inverse variance method for HR.
• To estimate the random effect model, the method of DerSimonian and Laird was used.
• The Higgins’ I2 index was computed to obtain a quantitative measure of the degree of inconsistency in the results of the studies included.
• A visual inspection of the funnel plot and the Harbord’s asymmetry test were used to assess the likelihood of publication bias.
Results
Characteristics of the studies
Breast cancer patients
Chemotherapy
Chemotherapy + LHRHa
Sverrisdottir et al.:
1) “Sverrisdottir 1”: chemotherapy + LHRHa vs chemotherapy alone
2) “Sverrisdottir 2”: chemotherapy + LHRHa + tamoxifen vs chemotherapy + tamoxifen
Elgindy et al.:
1) “Elgindy 1”: early chemotherapy alone vs early chemotherapy + LHRHa + LHRH antagonist 2) “Elgindy 2”: delayed chemotherapy vs delayed
chemotherapy + LHRHa
Characteristics of the studies
Author (year) No pts Median age (control vs experimental)
Hormone receptor status (pos/neg)
Type of LHRHa Definition of POF Timing of
POF
Li et al (2008)
63 NR NR Goserelin No resumption of menses NR
Badawy et al (2009)
78 29.2/30 NR Goserelin No resumption of menses and
ovulation
8 months
Sverrisdottir et al (2009)
123 45-45/45-46 NR Goserelin No resumption of menses 36 months
Del Mastro et al (2011-2014)
281 39/39 226/51 Triptorelin No resumption of menses and
postmenopausal levels of FSH and E2
12 months
Gerber et al (2011)
60 38.5/35.0 0/60 Goserelin No resumption of two consecutive
menstrual periods
6 months
Sun et al (2011)
100 33/32 NR Goserelin No resumption of menses NR
Munster et al (2011)
49 38/39 16/20 Triptorelin No resumption of menses 12 months
Elgindy et al (2013)
100 32.3-32.8/33.2-33.0 0/100 Triptorelin No resumption of menses 12 months
Song et al (2013)
183 40.3/42.1 150/33 Leuprolide Postmenopausal levels of FSH and E2
in the absence of menstrual activity
12 months
Karimi-Zarchi et al (2014)
42 37 0/42 Dipherelin No resumption of menses 6 months
Li et al (2014)
216 39/37.5 216/0 Goserelin Amenorrhea for the prior 12 months
and postmenopausal levels of FSH
12 months
Moore et al (2015)
218 38.7/37.6 0/218 Goserelin Amenorrhea for the prior 6 months
and postmenopausal levels of FSH
24 months
Results:
Premature Ovarian Failure
18.5% 33.5%
P < 0.001
Results:
Premature Ovarian Failure
Results:
One-Year Amenorrhea
31.0% 42.9%
P < 0.001
Results:
Patients with Pregnancy
9.2% 5.5%
P = 0.041
Results:
Disease-Free Survival
19.5% 18.8%
P = 0.939
• Temporary ovarian suppression with LHRHa in young breast cancer patients is associated with a reduced risk of
chemotherapy-induced POF and seems to increase the
pregnancy rate, without apparent negative consequence on prognosis.
• The use of LHRHa during chemotherapy might be considered a valid option for women interested in
preserving their ovarian function, and might also play a role in increasing the likelihood of becoming pregnant after
cessation of chemotherapy
Conclusions
Conclusions
Linee Guida AIOM Fertilità 2015
Conclusions
Acknowledgements
matteo.lambertini85@gmail.com
