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.

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

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

2013; 24(Suppl 6):vi160-70.

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

Study Background

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

Important News in 2015

Study Background

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

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.

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

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.

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

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).

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

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.

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

Results

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

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

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

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

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

Results: Premature Ovarian Failure

18.5% 33.5% P < 0.001

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

Results: Premature Ovarian Failure

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

Results: One-Year Amenorrhea

31.0% 42.9% P < 0.001

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

Results: Patients with Pregnancy

9.2% 5.5% P = 0.041

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

Results: Disease-Free Survival

19.5% 18.8% P = 0.939

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

• 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

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

Conclusions

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

Linee Guida AIOM Fertilità 2015

Conclusions

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

Acknowledgements

Congresso Nazionale AIOM Giovani 2016 Presented by: Matteo Lambertini, MD

matteo.lambertini85@gmail.com