Dr. Matteo Lambertini

Transcription

1 CONGRESSO NAZIONALE AIOM GIOVANI SESSIONE: PREMIAZIONE MIGLIORI TRE LAVORI GIOVANI 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 Dr. Matteo Lambertini U.O. Oncologia Medica 2 IRCCS AOU San Martino IST, Genova 8 luglio 2016 Perugia

2 Disclosure Information Relationship Relevant to this Session Lambertini, Matteo: No relevant relationship to disclose.

3 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 survivors 1. Embryo and oocyte cryopreservation are the standard procedure for fertility preservation 2,3. 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 fertility 2,3. 1. Poggio F et al, Expert Rev QoL Cancer Care 2016; 1: Loren AW et al, J Clin Oncol 2013; 31(19): Peccatori FA et al, Ann Oncol 2013; 24(Suppl 6):vi

4 Study Background Important News in 2015

5 Study Background

6 Lambertini M et al, Ann Oncol 2015; 26(12):

7 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 30 th, 2015; abstracts presented at ASCO, ASCO breast, SABCS and ESMO meetings were also searched.

8 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.

9 Study Objectives and Endpoints Primary objective: to compare the incidence of treatmentrelated 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).

10 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 I 2 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.

11 Results

12 Characteristics of the studies Chemotherapy Breast cancer patients 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

13 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) Badawy et al (2009) Sverrisdottir et al (2009) Del Mastro et al ( ) Gerber et al (2011) Sun et al (2011) Munster et al (2011) Elgindy et al (2013) Song et al (2013) Karimi-Zarchi et al (2014) Li et al (2014) Moore et al (2015) 63 NR NR Goserelin No resumption of menses NR /30 NR Goserelin No resumption of menses and ovulation 8 months /45-46 NR Goserelin No resumption of menses 36 months /39 226/51 Triptorelin No resumption of menses and postmenopausal levels of FSH and E /35.0 0/60 Goserelin No resumption of two consecutive menstrual periods 12 months /32 NR Goserelin No resumption of menses NR 6 months 49 38/39 16/20 Triptorelin No resumption of menses 12 months / /100 Triptorelin No resumption of menses 12 months / /33 Leuprolide Postmenopausal levels of FSH and E2 in the absence of menstrual activity 12 months /42 Dipherelin No resumption of menses 6 months / /0 Goserelin Amenorrhea for the prior 12 months and postmenopausal levels of FSH /37.6 0/218 Goserelin Amenorrhea for the prior 6 months and postmenopausal levels of FSH 12 months 24 months

14 Results: Premature Ovarian Failure P < % 33.5%

15 Results: Premature Ovarian Failure

16 Results: One-Year Amenorrhea P < % 42.9%

17 Results: Patients with Pregnancy P = % 5.5%

18 Results: Disease-Free Survival P = % 18.8%

19 Conclusions 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

20 Conclusions Linee Guida AIOM Fertilità 2015

21 Conclusions

22 Acknowledgements