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ANDROCUR

Opinions on drugs - Posted on Oct 22 2020

Reason for request

Reevaluation

Key points

Favourable opinion for reimbursement in:

  • hirsutism only in premenopausal women in the indication of severe hirsutism of non-tumoural origin in women (idiopathic, polycystic ovarian syndrome), when it has a severe impact on psycho-affective and social life and when satisfactory results have not been obtained following the use of medicinal products containing a lower dose of cyproterone acetate or other treatment options.
  • palliative antiandrogen therapy for prostate cancer.

Unfavourable opinion for reimbursement in hirsutism in postmenopausal women.

The clinical benefit is now moderate (previously it was substantial) in the treatment of hirsutism (only in the defined population, see below) and in palliative antiandrogen therapy for prostate cancer.

Role in the care pathway?

Hirsutism:

The French Endocrinology Society recommends cyproterone acetate, combined with an oestrogen, as a first-line treatment in the event of incapacitating severe hirsutism in premenopausal women.

Spironolactone (off-label), which must be combined with effective contraception, is the second-line treatment in the event of adverse effects, contraindications, patient refusal or a lack of efficacy of cyproterone acetate in premenopausal women.

In postmenopausal women, ANDROCUR (cyproterone acetate) is not recommended and alternative surgical solutions may be envisaged in the rare case when non-tumoural androgenic ovarian hyperactivity persists postmenopause.

Cosmetic measures enabling long-term hair removal may be proposed in combination with antiandrogen therapy: electrolysis or photoepilation.

Role of the medicinal product in the care pathway:

The Committee considers that:

  • in premenopausal women, providing that the recommendations issued are complied with (see special recommendations below), ANDROCUR (cyproterone acetate) retains a role in the treatment of severe hirsutism of non-tumoural origin in women (idiopathic, polycystic ovarian syndrome), when it has a severe impact on psycho-affective and social life and when satisfactory results have not been obtained following the use of medicinal products containing a lower dose of cyproterone acetate or other treatment options. The Committee has taken into consideration the substantial medical need in the absence of an available alternative for these patients.
  • in postmenopausal women, in view, firstly, of the increased risk of the development of meningioma demonstrated in this population by the available data (risk that increases with age) and, secondly, of the additional breast cancer risk (postmenopause with oestrogens combined with synthetic progestagens), ANDROCUR (cyproterone acetate) has no role in the treatment of hirsutism. In the rare case of androgenic ovarian hyperactivity, surgical solutions (salpingoophorectomy) may be envisaged.

Prostate cancer:

According to the 2020 guidelines of the National Comprehensive Cancer Network (NCCN), palliative antiandrogen therapy is aimed at patients with a life expectancy of ≤ 5 years with a high or very high risk of metastases, as well as patients in whom the disease progresses during the no therapy-monitoring phase, with the development of symptoms, or when the increase in PSA (prostate-specific antigen) suggests the imminent development of symptoms. It should be noted that the NCCN guidelines explicitly cite the nonsteroidal antiandrogens nilutamide, flutamide and bicalutamide, but do not mention cyproterone acetate. The European Society for Medical Oncology (ESMO) 2018 guidelines do not mention cyproterone acetate either in the palliative treatment of prostate cancer.

In its 2018 guidelines, the AFU (French Urology Association) highlights that the value of using cyproterone acetate lies in the management of hot flushes related to hormone treatment. Only incapacitating hot flushes should be managed using medicinal treatment.

Role of the medicinal product in the care pathway:

The role of ANDROCUR (cyproterone acetate) is very limited today in view of the alternatives available in palliative antiandrogen therapy for prostate cancer. The risk of meningioma is very limited with ANDROCUR in this indication, possibly due to the shorter exposure duration than in women for the treatment of incapacitating severe hirsutism. However, it should be highlighted that the other nonsteroidal antiandrogens currently used do not expose patients to this risk.

Overall, the Committee considers that cyproterone acetate retains a very limited role in the palliative treatment of prostate cancer, only as a salvage therapy for the management of incapacitating hot flushes related to hormone therapy.

Special recommendations

The Committee reiterates:

  • the importance of ensuring patients and healthcare professionals are well informed about the risks of meningiomas, the measures to be taken to prevent them, their detection and their treatment. Annual renewal of the information sheet co-signed by the patient and the doctor must be observed.
  • the need for any ANDROCUR 50 mg (cyproterone acetate) prescription to comply with the summary of product characteristics (SPC), particularly as regards investigation for the presence of meningiomas before starting treatment and regularly during treatment. Therefore a brain MRI should be performed at the start of treatment to verify the absence of meningioma. If treatment is continued for several years, brain imaging by MRI should be performed at most 5 years after the first MRI, then every 2 years if the 5-year MRI is normal.
  • the need to use the lowest effective dose of cyproterone acetate to the extent that this is possible, avoiding long-term use at high doses;
  • the need to permanently stop treatment if a meningioma is discovered.

Clinical Benefit

Moderate

The Committee deems that the clinical benefit of ANDROCUR 50 mg (cyproterone acetate) is moderate in premenopausal women in the indication “severe hirsutism of non-tumoural origin in women (idiopathic, polycystic ovarian syndrome), when it has a severe impact on psycho-affective and social life” and when satisfactory results have not been obtained following the use of medicinal products containing a lower dose of cyproterone acetate or other treatment options.

The Committee considers that the clinical benefit of ANDROCUR 50 mg (cyproterone acetate) is moderate in the indication of palliative antiandrogen therapy for prostate cancer.

Insufficient

The Committee deems that the clinical benefit of ANDROCUR 50 mg (cyproterone acetate) is insufficient to justify its reimbursement by public funding in view of the alternatives available in postmenopausal women in the indication “severe hirsutism of non-tumoural origin in women (idiopathic, polycystic ovarian syndrome), when it has a severe impact on psycho-affective and social life”.


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