Spotlight on triptorelin in the treatment of premenopausal women with early-stage breast cancer

Figures & data

Table 1 Randomized trials evaluating chemotherapy and chemotherapy ± ovarian suppression

Author	Year	Type of study	Patients (n)	Intervention	HR (n)	Primary endpoint	Hazard ratio	P-value
Castiglione-Gertsch et al^Citation27	2003	Randomized	1063	Goserelin CMF CMF → goserelin	ER negative (315)	5-Year DFS (%) (95% CI) 73% (64–84) 84% (77–91) 88% (83–91)	1.13 (0.83–1.53) 0.80 (0.57–1.11) 0.71 (0.52–0.99)	0.44 0.17 0.04
				Goserelin CMF CMF → goserelin	ER positive (720)	81% (76–87) 81% (76–87) 86% (82–91)	1.52 (0.89–2.58) 0.75 (0.40–1.39) 0.49 (0.28–0.87)	0.12 0.35 0.01
Davidson et al^Citation28	2005	Randomized	1503	CAF CAF → goserelin CAF → goserelin plus tamoxifen	ER positive	9-Year DFS (%) 57% 60% 68%	0.93 (0.76–1.12) 0.74 (0.60–0.91)	0.22 <0.01
Arriagada et al^Citation29	2005	Randomized	926	Chemotherapya Chemotherapya plus ovarian suppressionb	ER positive	10-Year OS (%) (95% CI) 68% (63–73) 66% (61–70)	1.2 (0.9–1.7)	0.19
Kaufmann et al^Citation30	2007	Randomized	776	Chemotherapyc followed by goserelin Standard chemotherapy Chemotherapy followed by goserelin Standard chemotherapy	ER negative (465) ER positive (311)d	5-Year EFS (%) (95% CI) 30.8% 30.7% 20.6% 25.8%	1.01 (0.72–1.42) 0.77 (0.47–1.24)	0.97 0.27
Baum et al^Citation31e	2006	Meta-analysis	2710	Standard adjuvant therapy Adjuvant therapy plus goserelin	ER positive	5-Year EFS (%) (95% CI) 69.4% 74.6%	0.80 (0.69–0.92)	0.002
Adjuvant Breast Cancer Trials Collaborative Group^Citation32	2007	Randomized	2144	5 years tamoxifen (± chemotherapyf) + OASg 5 years tamoxifen (± chemotherapyf)	ER positive	5-Year OS (%) (95% CI) 82.6% (80–84.9) 80.3% (77.5–82.9)
Roché et al^Citation33	2006	Randomized	333	Triptorelin plus tamoxifen FEC50	ER positive	7-Year DFS (%) (95% CI) 76 (68–84) 72 (65–88)	0.94 (0.78–1.13)	0.44

Notes:

a CAF/FEC/CMF.

b Ovarian radiation, surgical oophorectomy, or triptorelin.

c N4-9: 4´ EC +3´ CMF.

d HR-positive patients enrolled after protocol amendment.

e Patients younger than 50 years.

f CMF/anthracycline containing/others.

g Ovarian radiation, surgical oophorectomy, or LHRH agonist (triptorelin or leuprorelin acetate).

Abbreviations: CI, confidence interval; DFS, disease-free survival; HR, hormone receptor; LHRH, luteinizing hormone-releasing hormone; OS, overall survival; CAF, cyclophosphamide, doxorubicin, 5-fluorouracil; FEC, 5- fluorouracil, epirubicin, cyclophosphamide; CMF, cyclophosphamide, methotrexate, 5 fluorouracil; OAS, ovarian ablation or suppression; ER, estrogen-receptor; EFS, event-free survival.

Table 2 Ovarian function suppression and outcome results

Author	Year	Patients (n)	Treatment arms	DFS (%)a	HR (95% CI)	P-value
Pagani et al^Citation66	2017	4690	Exemestane + OFS	86.8	0.77 (0.67–0.90)	0.0006
Francis et al^Citation62	2015	3066	Tamoxifen + OFS Tamoxifen + OFS Tamoxifen	82.8 86.6 84.7	0.83 (0.66–1.04)	0.10
Lambertini et al^Citation72	2015	281	CT + triptorelin CT alone	80.5 83.7	1.17 (0.72–1.92)	0.52
Moore et al^Citation89	2017	218	CT + goserelin CT alone	88.0 79.0	0.50 (0.24–0.97)	0.05

Note:

a 5-Year DFS.

Abbreviations: CI, confidence interval; CT, chemotherapy; DFS, disease-free survival; HR, hazard ratio; OFS, ovarian function suppression.

Figure 1 TEXT study description.

Notes: OFS achieved using triptorelin 3.75 mg every 28 days. Bilateral oophorectomy or ovarian irradiation was allowed at least 6 months of triptorelin after randomization. Optional chemotherapy: if administered was started concomitantly with triptorelin followed by oral endocrine therapy after the completion of chemotherapy. If chemotherapy was not administered, oral endocrine therapy was started 6–8 weeks after the initiation of triptorelin.
Abbreviations: EBC, early breast cancer; HR, hormone receptor; OFS, ovarian function suppression; TEXT, Tamoxifen and Exemestane Trial.

Figure 2 SOFT trial study description.

Notes: OFS achieved using triptorelin 3.75 mg every 28 days, bilateral oophorectomy or ovarian irradiation. Patients randomized to receive endocrine therapy ± OFS between 12 weeks of surgery or within 8 months of neoadjuvant chemotherapy.
Abbreviations: EBC, early breast cancer; HR, hormone receptor; OFS, ovarian function suppression; SOFT, Suppression of Ovarian Function Trial.

Table 3 Triptorelin and ovarian function preservation

Author	Year	Patients randomized (control/experimental)	Median age, years (control/experimental)	HR status (positive/negative)	Endocrine therapy + triptorelin	Definition of POF	Timing of POF evaluation (months)	OR for POF defined as amenorrhea 1 year after the end of chemotherapy (95% CI)
Del Mastro et al^Citation71	2011	133/148	39/39	26/51	Tamoxifen	No resumption of menses and postmenopausal levels of FSH and E2	12	0.56 (0.35–0.90)
Lambertini et al^Citation97	2014
Munster et al^Citation94	2012	38/39	32/33	16/20	Tamoxifen	No resumption of menses	12	0.74 (0.21–2.58)
Elgindy et al^Citation98,a	2013	50/50	40/42	0/100	–	No resumption of menses	12	0.76 (0.18–3.25) 1.00 (0.25–4.00)

Notes:

a This study was analyzed considering the following comparisons: early chemotherapy-alone vs early chemotherapy + LHRHa + LHRH antagonist (ie, “Elgindy 1”) and delayed chemotherapy vs delayed chemotherapy + LHRHa.

Abbreviations: CI, confidence interval; E2, estradiol; FSH, follicle-stimulating hormone; HR, hormone receptor; LHRH, luteinizing hormone-releasing hormone; LHRHa, LHRH analog; POF, premature ovarian failure.

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