A combination of oral Lynparza (olaparib) and weekly chemotherapy can be safely given to heavily treated ovarian cancer patients and shows signs of efficacy, particularly among those with BRCA mutations, a Phase 1/2 trial shows.
The findings suggest that weekly chemotherapy might be more suitable for these patients than the standard every-three-week dosing, and should be investigated in larger Phase 3 trials.
The study, “Phase Ib with expansion study of olaparib plus weekly (Metronomic) carboplatin and paclitaxel in relapsed ovarian cancer patients,” was published in the International Journal of Gynecological Cancer.
Lynparza, marketed by AstraZeneca and the first PARP inhibitor used to treat ovarian cancer, has come to significantly improve the outcomes of these patients. However, initial attempts to combine Lynparza with standard chemotherapy regimens were disappointing, with most patients experiencing severe toxicity.
Chemotherapy with Paraplatin (carboplatin) and Taxol (paclitaxel) is usually given once every three weeks to ovarian cancer patients. But studies suggest that a weekly regimen might be safer, with patients reporting better quality of life scores and fewer adverse events.
Researchers conducted a Phase 1/2 trial (NCT01650376) to assess the feasibility of combining Lynparza and weekly chemotherapy in heavily-treated women with ovarian cancer.
In the first of this two-part study, researchers tested escalating doses of Lynparza, along with chemotherapy, to determine the safest dose for additional testing. The recommended dose — 150 mg tablets twice daily each week, on first three days of each week — was then tested in a larger group of patients to determine its efficacy and to continue assessing safety.
Patients in both groups who achieved a partial or complete response were then offered maintenance therapy with Lynparza alone until their disease worsened.
The trial included 54 women, with a median age of 58 and advanced disease: 14 were enrolled in Phase 1, and 40 in Phase 2. Among them, 54% responded to the treatment, including 24% (13 patients) who had complete responses that lasted a median of 10.3 months. An additional 20% (11 women) had their disease stabilized.
Survival outcomes were better for patients with mutations in their BRCA genes — known to increase the sensitivity to PARP inhibitors like Lynparza. These patients lived without disease worsening for a median of 12.1 months – versus 4.8 months for those without mutations – and remained alive for a median of 21.1 months, as opposed to 10.4 months.
Overall, 26% of patients experienced a life-threatening event, but treatment was deemed well-tolerated, with only four patients stopping treatment due to toxicity. At 39 and 58 months, two patients with BRCA mutations in complete remission were still taking Lynparza.
“In summary, olaparib tablets can be safely administered simultaneously with a regimen of metronomic carboplatin with paclitaxel in heavily pre-treated relapsed ovarian cancer patients,” researchers concluded. “This trial provides a reasonable option for this patient population and appears to be most efficacious in [BRCA mutated] patients.”
“Future trials could incorporate our regimen in evaluating the benefit of combination chemotherapy in patients with platinum-sensitive ovarian cancer in first relapse,” they added.