LYNPARZA (olaparib) - Ovarian cancer

The Committee deems that the clinical benefit of LYNPARZA (olaparib), in association with bevacizumab, remains substantial in the MA indication.

In view of:

• the findings of the randomised, double-blind phase 3 study;
• providing evidence of the superiority of the association of olaparib + bevacizumab versus placebo + bevacizumab, in terms of:
  • investigator-assessed progression-free survival: HR=0.33 [95%CI: 0.25-0.45], with a median progression-free survival of 37.2 months [95%CI: 36.0-NE] in the olaparib + bevacizumab group versus 17.7 months [95%CI: 15.8-19.9] in the placebo + bevacizumab group, i.e. a point estimation of the absolute difference of 19.5 months;
  • overall survival: HR=0.62 [95%CI: 0.45-0.85], with a median overall survival of 75.2 months [95%CI: 73.3-NA] in the olaparib + bevacizumab group versus 57.3 months [95%CI: 51.6-NA] in the placebo + bevacizumab group, i.e. a point estimation of the absolute difference of 17.9 months;
• in subgroup analyses conducted on HRD+ patients for whom interaction tests between treatment effect and HRD status were significant, expressing a different effect of olaparib + bevacizumab on progression-free survival and overall survival according to HRD status.

and despite:

• the lack of stratification of randomisation on HRD status, liable to give rise to confounding bias in these estimations;
• the persistence of certain limitations highlighted in the initial opinion, such as the additional toxicity, the onset of myelodysplastic syndromes/acute myeloid leukaemia, and the lack of formal conclusion that can be drawn from the quality-of-life findings;

the Committee deems that LYNPARZA (olaparib) in association with bevacizumab provides moderate clinical added value (CAV III) in relation to bevacizumab monotherapy for the maintenance treatment of adult patients with advanced (FIGO stage III and IV) ovarian, fallopian tube or primary peritoneal epithelial cancer with a partial or complete response to a first line of treatment associating platinum-based chemotherapy with bevacizumab and whose cancer is associated with a positive homologous recombination deficiency (HRD) status, defined by a BRCA 1/2 gene mutation and/or genomic instability.