Rucaparib boosts progression-free survival in BRCA mutant recurrent OC
Rucaparib maintenance therapy increases progression-free survival in BRCA mutant recurrent ovarian cancer (OC) by 77%, according to late-breaking results from the ARIEL3 trial reported today at the ESMO 2017 Congress in Madrid.
Most ovarian cancer presents as advanced disease and 80% of those patients will recur after first line treatment.
The PARP enzyme helps to initiate the repair of DNA damage so that cells can continue to divide. DNA repair processes are inherently impaired in tumour cells with BRCA mutations. PARP inhibitors, such as rucaparib, block DNA repair and cells with BRCA mutations die.
Just over 20% of patients with ovarian cancer have BRCA mutations and are susceptible to PARP inhibitors. Some others with the disease are also susceptible, such as patients who respond to platinum-based chemotherapy and those with a high degree of genomic loss of heterozygosity (LOH) – meaning the tumour DNA is scarred and DNA repair mechanisms are faulty.
ARIEL3 included 564 patients with high grade ovarian cancer who had responded to platinum-based chemotherapy in the second or third line of treatment. Patients were randomised 2:1 to rucaparib, maintenance therapy or placebo. The primary endpoint was progression-free survival, which was measured sequentially in three groups if benefit was found in the previous group: 1) BRCA mutant; 2) BRCA mutant or BRCA wild type with high LOH (together called homologous recombination deficient or HRD); 3) intention to treat (entire study population).
Rucaparib led to a statistically significant improvement in progression-free survival in all three groups. Progression-free survival increased from 5.4 months to 16.6, 13.6, and 10.8 months in groups 1, 2, and 3, respectively, with hazard ratios of 0.23, 0.32, and 0.36, respectively.
In exploratory analyses, patients without BRCA mutations (wild type) were divided into those with high and low LOH. As expected, patients with high LOH had more improvement in progression-free survival than those with low LOH. But in both high and low LOH subgroups, rucaparib was statistically significantly better than placebo. Rucaparib was well tolerated and just 13% of patients had to discontinue the medication due to side effects. The safety profile of rucaparib in ARIEL3 was consistent with previous phase II studies.
# LBA40_PR Ledermann J et al: ARIEL3: A Phase 3, Randomised, Double-Blind Study of Rucaparib vs Placebo Following Response to Platinum-Based Chemotherapy for Recurrent Ovarian Carcinoma (OC)
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