medwireNews: Maintenance therapy with olaparib, given in the newer tablet formulation, significantly improves progression-free survival (PFS) compared with placebo in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation, phase III trial data show.
“The improvement in progression-free survival seen using the olaparib tablet formulation in this disease setting is compelling because patients were able to maintain a good quality of life while experiencing a delay in disease progression and, therefore, a delay until the symptoms associated with subsequent chemotherapy treatments,” Eric Pujade-Lauraine (Université Paris Descartes, France) and fellow SOLO2/ENGOT-Ov21 investigators remark.
They add that “[t]he new tablet formulation of olaparib reduced the pill burden from 16 capsules to four tablets per day while maintaining similar or higher exposure, providing patients with a simpler, more convenient treatment regimen.”
For the study, 295 women aged 18 years or older with relapsed, high-grade serous ovarian cancer or high-grade endometrioid cancer with a BRCA1/2 mutation were randomly assigned to receive the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib (300 mg in two 150 mg tablets, twice daily; n=196) or matching placebo tablets (n=99) until disease progression or the point when the patient was no longer receiving benefit from treatment.
The preliminary findings, using immature data, show that treatment with olaparib was associated with a significant 70% reduced risk for disease progression or death compared with placebo, with respective median PFS times of 19.1 and 5.5 months.
Significant improvements with olaparib versus placebo were also observed for the secondary endpoints of median time to first subsequent therapy (27.9 vs 7.1 months), median time to second progression (not reached vs 18.4 months), and median time to second subsequent therapy (not reached vs 18.2 months).
Median overall survival was not reached for either treatment group, and there was no significant difference in mortality rates, at 23% (n=45 deaths) for olaparib and 27% (n=27 deaths) for placebo. However, the researchers emphasize that the data were immature and say that a “preplanned analysis of overall survival at approximately 60% maturity (~177 overall survival events) will provide further information.”
Pujade-Lauraine et al also report that there was no significant difference in health-related quality of life between the two groups, and the safety profile with the olaparib tablets was similar to that seen with the capsule formulation.
The most common grade 3 or worse adverse event was anemia, occurring in 38 patients in the olaparib group, 35 of whom needed a blood transfusion. By comparison, two patients in the placebo group had grade 3 anemia and one needed a blood transfusion.
One patient in the olaparib group developed acute myeloid leukemia, which resulted in death and was classed as a treatment-related grade 5 adverse event.
Writing in The Lancet Oncology, Pujade-Lauraine and co-authors conclude: “The SOLO2 data support use of the olaparib tablet formulation.”
In an accompanying comment, Michael Bookman (US Oncology Research, Tucson, Arizona, USA) and Henry Kitchener (University of Manchester, UK) say that “PARP inhibitors represent an important class of drugs for use in recurrent ovarian cancer.”
They add: “Combinations of PARP inhibitors with other agents have become a priority for innovative research, to optimise the potential benefit of immunotherapeutics, anti-angiogenic agents, or drugs targeting DNA damage response pathways.
“These trials will hopefully extend the benefit of PARP inhibitors to patients with less favourable molecular and clinical profiles.”
By Laura Cowen
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