Lynparza (olaparib) Phase III SOLO-2 data demonstrated progression-free survival benefit in BRCA-mutated ovarian cancer as maintenance therapy.
AstraZeneca on Tuesday presented results from the Phase III SOLO-2 trial demonstrating a significant improvement in progression-free survival (PFS) in germline BRCA-mutated (gBRCA), platinum-sensitive, relapsed ovarian cancer patients treated with Lynparza (olaparib) tablets (300mg twice daily), compared with placebo in the maintenance setting. The trial met its primary endpoint of investigator-assessed PFS (HR 0.30; 95% CI 0.22-0.41; P<0.0001; median 19.1 months vs 5.5 months).1
PFS as measured by Blinded Independent Central Review (BICR) evaluation, a pre-specified sensitivity analysis supporting the primary endpoint, demonstrated a median PFS of 30.2 months vs 5.5 months for placebo, representing an improvement of 24.7 months (HR 0.25; 95% CI 0.18-0.35; P<0.0001).1
Additionally, a statistically-significant benefit in time to second progression or death (PFS2) was also seen in patients treated with Lynparza (HR 0.50; 95% CI 0.34-0.72; P=0.0002; median not reached vs 18.4 months), compared with placebo, as well as improvements in other key secondary endpoints.1
These results, presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in National Harbor, MD, build upon prior data in this setting, demonstrating the potential of Lynparza as a maintenance therapy in relapsed ovarian cancer.1,2
Richard Penson, M.D., Associate Professor of Medicine at Harvard Medical School and Clinical Director of Medical Gynecologic Oncology at Massachusetts General Hospital said: “The SOLO-2 data demonstrated a statistically significant and clinically meaningful improvement in outcomes for those who took olaparib. The results, which showed a delay in disease progression in the maintenance setting, highlight the impact of PARP inhibition at the forefront of the important advances we are making in targeting ovarian cancer.”
Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “We are extremely pleased with the results from SOLO-2, which support the potential benefit of Lynparza tablets as a maintenance therapy for patients with relapsed ovarian cancer. The tablet formulation may offer patients a reduced pill burden for Lynparza and a safety profile that is generally consistent with previous trials. We will work with regulatory authorities to make Lynparza tablets available to patients as quickly as possible.”
The safety profile for patients treated with Lynparza tablets during the trial was generally consistent to those observed with the currently-approved capsule formulation.1 Any adverse events (AE) Grade ≥3 were reported in 36.9% of patients treated with Lynparza and in 18.2% of patients who received placebo.1 The most common non-hematological AEs reported at a frequency of ≥20% in the Lynparza arm versus placebo were nausea (75.9% vs 33.3%), fatigue/asthenia (65.6% vs 39.4%), and vomiting (37.4% vs 19.2%).1 Grade ≥3 non-hematological AEs reported at a frequency of ≥2.5% in the Lynparza arm versus placebo were fatigue/asthenia (4.1% vs 2.0%), vomiting (2.6 % vs 1.0%), abdominal pain (2.6% vs 3.0%), nausea (2.6% vs 0.0%), diarrhea (1.0% vs 0.0%), and constipation (0.0% vs 3.0%).1
The most common hematological AEs reported in the Lynparza arm versus placebo were anemia (43.6% vs 8.1%), neutropenia (19.5% vs 6.1%), and thrombocytopenia (13.8% vs 3.0%).1 Grade ≥3 hematological AEs reported in the Lynparza arm versus placebo were anemia (19.5% vs 2.0%), neutropenia (5.1% vs 4.0%), and thrombocytopenia (1.0% vs 1.0%).1
The 300mg twice-daily tablet dose potentially reduces the pill burden for patients from 16 capsules to four tablets per day.
Lynparza tablets are an investigational formulation and are not FDA-approved for any use.3,4 Lynparza capsules (400mg twice daily) are currently approved in the U.S. as a monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-approved test) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. The indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
1 Pujade-Lauraine E., Ledermann J., Penson R., et al., Treatment with olaparib monotherapy in the maintenance setting significantly improves progression-free survival in patients with platinum-sensitive relapsed ovarian cancer: Results from the Phase III SOLO-2 Study. Presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO), March 12 – 15. National Harbor, MD.
2 Ledermann J., Harter P., Gourley M., et al., Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer. N Engl J Med 2012;366:1382-92.
3 Lynparza (olaparib) Prescribing Information. AstraZeneca Pharmaceuticals LP, Wilmington, DE.
4 National Institutes of Health. Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy. Available Online. Accessed March 2017.
(Source: Business Wire)
Filed Under: Drug Discovery