LYNPARZA (olaparib) - HER2-negative, high-risk early breast cancer

Opinions on drugs - Posted on Feb 10 2023

Reason for request

Indication extension

New indication.

Key points

Favourable opinion for reimbursement of LYNPARZA (olaparib) indicated: “as monotherapy or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline BRCA1/2-mutations who have HER2-negative, high-risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy”.

What therapeutic improvement?

Therapeutic improvement in the care pathway.

Role in the care pathway?

The Committee deems that LYNPARZA (olaparib) as monotherapy or in combination with endocrine therapy is an adjuvant treatment for adult patients with germline BRCA1/2-mutations who have HER2-negative, high-risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy. In patients with triple-negative breast cancer (stages 2 and 3), KEYTRUDA
(pembrolizumab) is also recommended in the subgroup of patients eligible for this treatment. In the absence of available comparative data, it is not possible to specify the role of LYNPARZA (olaparib) compared to KEYTRUDA (pembrolizumab).

In addition, given the important potential risk of acute myeloid leukaemia/myelodysplastic syndrome, the Committee recommends careful investigation of any unexplained cytopenia developing during treatment with olaparib as monotherapy or in combination via appropriate haematological investigations, such as a myelogram and a cytogenetic analysis of the bone marrow in order not to miss a potential diagnosis of MDS or AML (see 4.4 Special warnings and precautions for use in the SmPC).

Special recommendations

The Committee would like to receive longer-term results on overall survival (additional analysis of overall survival scheduled in 2024) and the final study results (final analysis scheduled in 2029).

Clinical Benefit

Substantial

The clinical benefit (CB) of LYNPARZA (olaparib) is substantial in this MA indication extension.

Clinical Added Value

moderate

Considering:

demonstration of a superiority of adjuvant treatment with olaparib (LYNPARZA) compared to placebo in the Olympia phase 3 study, in terms of:
- invasive disease-free survival (with 11.5% of patients having presented invasive disease-free survival events in the olaparib group versus 19.5% of patients in the placebo group, i.e. a difference of 8 points in favour of olaparib; HR=0.58; CI99.5% = [0.41 - 0.82],
  p = 0.0000073);
- overall survival (with 8.1% of patients having died in the olaparib group versus 11.9% of patients in the placebo group, i.e. an absolute difference of 8 points in favour of olaparib; HR=0.68; CI98.5% = [0.47 - 0.97], p = 0.009);

despite:

an additional toxicity primarily concerning adverse events of grades > 3, with 24.5% in the olaparib group versus 11.3% in the placebo group;
the risk of myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML), identified as important potential risks in the Risk Management Plan (RMP) and in a context of treatment at an early stage of the disease;
the limited follow-up time (median follow-up of 3.5 years), which requires longer-term follow-up to confirm the benefit observed, particularly relative to overall survival;
the absence of a formal conclusion that can be drawn on quality of life (exploratory endpoint);

the Committee deems that LYNPARZA (olaparib) provides a moderate clinical added value (CAV III) in the care pathway for the treatment of adult patients with germline BRCA1/2-mutations who have HER2-negative, high-risk early breast cancer previously treated with neo-adjuvant or adjuvant chemotherapy, not including the comparator KEYTRUDA (pembrolizumab) for the subgroup concerned.

Avis économique

Ce produit a fait l'objet d'un avis économique rendu par la Commission d'évaluation économique et de santé publique le 6 juin 2023. L’avis économique porte sur une indication superposable à celle demandée au remboursement, à savoir le traitement adjuvant chez les patients adultes atteints d'un cancer du sein précoce à haut risque HER2 négatif et présentant une mutation germinale des gènes BRCA1/2 et qui ont été précédemment traités par chimiothérapie néoadjuvante ou adjuvante

Au prix retenu dans la modélisation et sous les hypothèses retenues par l’industriel, le RDCR estimé est de 35 329 €/QALY pour olaparib par rapport à la surveillance active dans le sous-groupe histologique TNBC ; et de 23 950 €/QALY pour olaparib par rapport à la surveillance active dans le sous-groupe histologique HR+/HER2. sur un horizon temporel de 43 ans.

Une analyse d’impact budgétaire a été fournie dans le cadre de ce dossier.

> LINPARZA - Avis économique (pdf)

Documents

Economic analysis

English version

LYNPARZA_18012023_SUMMARY_CT19971

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