Evaluating triptorelin as a treatment option for breast cancer

ABSTRACT

Introduction: Triptorelin is a luteinizing hormone-releasing hormone analog (LH-RHa) inducing ovarian function suppression (OFS). It is approved by FDA and EMA in association with tamoxifen or aromatase inhibitor (AI) and with fulvestrant and palbociclib in premenopausal women with hormone receptor (HR)-positive breast cancer. Its potential role to preserve ovarian function during chemotherapy has also been recently clarified.

Areas covered: Several studies have investigated the role of adding OFS to tamoxifen and aromatase inhibitors as adjuvant treatment in early breast cancer. The addition of triptorelin is not free from adverse events as the combination with tamoxifen and exemestane resulted in an increase of endocrine-deprivation symptoms. Clinical trials have explored the combination of LH-RHa with chemotherapy in fertility preservation, demonstrating no detrimental effect on patients’ oncological outcome. This is all discussed in this evaluation.

Expert opinion: Triptorelin represents a standard-of-care in premenopausal women with HR-positive breast cancer and in some cases of male breast cancer. In the adjuvant setting, a personalized approach is required to combine LH-RHa with the right partner considering the risk of recurrence and the toxicity profile. LH-RHa may be offered to breast cancer patients in the hope of reducing the likelihood of chemotherapy-induced ovarian insufficiency.

KEYWORDS:

• Triptorelin
• ovarian function suppression
• luteinizing hormone-releasing hormone analog
• ovarian function preservation

Article highlights

• LHRHa including triptorelin are approved in association with tamoxifen or AI and with fulvestrant and palbociclib in premenopausal women and in male patient with hormone receptor (HR) positive breast cancer, both in early and advanced setting.

• The antitumor effect of triptorelin and other LH-RHa occurs through reduction of estrogen serum level and interfering directly with the MAP kinase pathway and c-FOS expression on tumoral cells.

• In the advanced setting, the benefit of combining LHRHa with endocrine treatment was observed in terms of survival, progression-free-survival and, evermore, of objective response rate with value between 30 to 40%.

• In the adjuvant setting, a benefit in terms of survival of adding LHRHa to standard adjuvant therapy (chemotherapy with or without endocrine treatment) in pre-menopausal women with HR-positive early breast cancer has been demonstrated.

• SOFT and TEXT studies showed that the addition of OFS to tamoxifen resulted in a 24% lower relative risk of recurrence, compared with tamoxifen alone, with an absolute difference of 4.2% in the rate of disease-free survival at 8 years.

• LHRHa are well tolerated and the possible adverse events are related to the deprivation of estrogen.

• The best partner of OFS in high-risk patients remains controversial and the choice of endocrine therapy should be tailored for each patient.

• LH-RHa are suggested in combination with chemotherapy, regardless HR status, as a complement of other fertility preservation methods, considering the decrease of premature ovarian insufficiency with no detrimental effect on patients ‘oncological outcome.

Box 1. Drug summary box.

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Declaration of interest

G Curigliano is on the advisory boards of Eli Lilly and Company, Roche, Novartis, Pfizer Inc, SeaGen International GmbH and Ellipses. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One referee declares that they received payments for speaking and for their participation on advisory boards from Celgene, Eli Lilly and Company, Pfizer and Novartis. They have also received payments for travel expenses from Pfizer, Roche and Pierre Fabre. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript has not been funded.