Curing advanced ovarian cancer; now on the horizon
Ovarian cancer is the 3rd most common malignancy diagnosed in Indian women. GLOBOCAN data indicates that around 45000 women in India developed ovarian cancer in 2020 and 32000 women succumbed to this illness. Majority of ovarian cancers are diagnosed at an advanced stage which has a high risk of relapse. 70% of patients relapse within 3 years and the 5 year survival is only 30-50%. Once relapse occurs, the disease is incurable.
PARP inhibition (poly(ADP-ribose) polymerase) has emerged as the most significant therapeutic advance in the last decade for treating advanced ovarian cancers. Patients who have a defect in the Homologous recombination repair (HRR) pathway for repairing double stranded DNA breaks because of loss-of-function mutations in either BRCA 1 or BRCA 2 are particularly sensitive to PARP inhibitors as the PARP enzyme is critical for repairing single-strand DNA breaks.
Olaparib is a first-in-class, oral PARP inhibitor. Recently, the 5 year results of the SOLO1/GOG 3004 study were published in The Lancet Oncology. 391 newly diagnosed advanced (FIGO Stage III/IV) ovarian cancer cases with a germline or somatic BRCA 1/2 mutation were randomized to either 24 months of oral olaparib or placebo after completion of cytoreductive surgery and first line platinum based chemotherapy.
At a median follow up of 5.0 years, the olaparib arm had a median progression-free survival of 56.0 months versus 13.8 months with placebo. Remarkably, this benefit was sustained for several years even after completing 2 years of maintenance olaparib. The most common severe side effects were anemia (22%), neutropenia (8%) and fatigue (4%). A rare side effect of the drug is myelodysplastic syndrome/acute myeloid leukemia which was reported in 1% of patients
TAKE HOME MESSAGE
PARP inhibition in BRCA 1/2 mutated advanced ovarian cancer has shown that a potential cure is possible. Genetic testing for ovarian cancer patients is the recommended standard of care.