Positive CHMP opinion for rucaparib in advanced ovarian cancer

20th October 2023

Rucaparib has been given a positive opinion as a first-line maintenance treatment for patients with advanced ovarian cancer by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP), its manufacturer Pharma& has announced.

Suitable for all women with advanced ovarian cancer, regardless of BRCA mutation status, who have responded to first-line platinum-based chemotherapy, rucaparib (brand name Rubraca) is a poly-ADP ribose polymerase (PARP) inhibitor.

The targeted cancer drug is currently approved as a monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who have a complete or partial response to platinum-based chemotherapy.

The recent recommended approval from the CHMP is a Type II variation on the current license and is based on the randomised, double-blind, placebo-controlled, phase 3 ATHENA-MONO trial results.

The trial demonstrated that rucaparib significantly improved investigator-assessed progression-free survival compared with placebo in women, regardless of their BRCA mutation status in each of the populations studied.

The safety profile observed in the ATHENA-MONO trial was consistent with both the current US and European labels for rucaparib.

Dr Rebecca Kristeleit, consultant medical oncologist and adjunct reader at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London, and European Network of Gynaecological Oncological Trial (ENGOT) lead of the ATHENA trial, said: ‘In the ATHENA-MONO trial, rucaparib prolonged progression-free survival, irrespective of molecular characteristics, and its potential approval by the European Medicines Agency as a first-line maintenance treatment is an important step forward in this difficult-to-treat population.

‘Women with advanced ovarian cancer need and deserve new treatment options to improve outcomes, and [this] recommendation is hopeful news for eligible patients in Europe.’

The European Commission will now review the positive opinion and Pharma& anticipates an approval decision in the coming months.

Elmar Zagler, founder and managing director, Pharma&, said: ‘Accessing effective medicines is the primary goal for both healthcare providers and patients, and it can be devastating when these medicines are no longer available.

‘Over the last five years, Pharma& has established itself as an agile, fully integrated global company that aspires to breathe new life into proven medicines like rucaparib.’

Earlier this year, rucaparib was found to improve progression-free survival in metastatic, castration-resistant prostate cancer with BRAC alteration compared to usual care.

Rucaparib offers survival advantage over usual care in metastatic prostate cancer

1st March 2023

Rucaparib improves progression-free survival in metastatic, castration-resistant prostate cancer with BRAC alteration compared to usual care.

Rucaparib in men with metastatic, castration-resistant prostate cancer and BRAC alteration improved progression-free survival compared to physician’s choice of treatment according to the findings of a randomised trial by the TRITON3 investigators.

The five-year survival of men diagnosed with metastatic prostate cancer has been estimated to be around 28%. Moreover, the presence of inherited mutations in DNA-repair genes such as BRCA2, increase the risk of the cancer being lethal with one analysis finding that such mutations were detected in nearly 12% of metastatic prostate cancers.

In fact, the presence of BRAC 1 and 2 mutations are associated with poor survival outcomes in men with prostate cancer.

The enzyme poly(ADP-ribose) polymerase facilitates DNA repair by binding to DNA breaks and attracting DNA repair proteins to the site of damage. Furthermore, use of PARP inhibitors to selectively kill a tumour, represents a new concept in cancer treatment.

In a phase 2 trial (TRITON2), the use of oral rucaparib, which is a PARP inhibitor, showed that the drug had anti-tumour activity in men with metastatic, castration-resistant prostate cancer and a deleterious BRAC alteration.

In the current study, researchers sought to be build on the success of TRITON2. They undertook a phase 3 trial in men with metastatic, castration-resistant prostate cancer and a BRCA1, BRCA2, or ataxia telangiectasia mutated (ATM) alteration, whose disease had progressed after use of a second-generation androgen-receptor pathway inhibitor.

Participants were randomised 2:1 to oral rucaparib (600 mg twice daily) or a physician’s choice control which was docetaxel or abiraterone acetate or enzalutamide.

The primary outcome as the median duration of imaging-based progression-free survival according to independent review.

Rucaparib and progression-free survival

A total of 405 men with a median age of 70.5 years were randomised to rucaparib (270) or control. In the rucaparib arm, 201 patients had a BRAC alteration.

After 62 months, the median duration of progression-free survival in those with a BRAC alteration was 11.2 months compared to 6.4 months in the control arm (Hazard ratio, HR = 0.50, 95% CI 0.36 – 0.69, p < 0.001).

Similarly, among the intention-to-treat group, survival was also significantly longer (HR = 0.61, 95% CI 0.47 – 0.80, p < 0.001). However, in an exploratory analysis, the median duration of progression-free survival in the ATM subgroup was not significantly lower (HR = 0.95, 95% CI 0.59 – 1.52).

Citation
Fizazi K et al. Rucaparib or Physician’s Choice in Metastatic Prostate Cancer. N Eng J Med 2023.