Lynparza as maintenance therapy for BRCA-mutated ovarian cancer patients

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Ovarian cancer is the 7th most commonly diagnosed cancer in women worldwide1 and the 5th most common cause of cancer deaths in this population.2 There is an increased risk of ovarian cancer in women with germline mutations in BRCA1 or BRCA2.3

Olaparib marketed by Astra Zeneca as Lynparza is a PARP inhibitor. PARP is a short form of Poly (ADP-ribose) polymerase, a protein that helps in the repair of damaged cells and their DNA. Furthermore, the cancer cells with a change in BRCA gene depend on PARP for their DNA repair and health.4 Olaparib and other PARP inhibitors block the actions of PARP protein because which cancer cells are unable to repair their damaged DNA and die eventually.5

Lynparza (Olaparib) has already been approved by the US FDA in December 2014 as the first monotherapy for patients with deleterious or suspected deleterious germline BRCA-mutated, advanced ovarian cancer, who have been treated with three or more prior lines of chemotherapy.6

AstraZeneca, on 14th March 2017 presented results from the Phase III SOLO-2 trial which support the potential benefit of Lynparza with significant improvement in PFS in germline BRCA-mutated, platinum-sensitive, relapsed ovarian cancer as maintenance therapy, as compared with placebo.7

The trial was randomized and double blinded and enrolled 295 patients with BRCA1 or BRCA2 mutations who had received at least two lines of platinum based chemotherapy with a partial or complete response. Parameters such as median progression free survival (the length of time tumours did not grow after treatment) and hazard ratio were measured in the trial.7

The blinded reviewers found that patients taking Lynparza showed a median PFS of 30.2 months vs 5.5 months for those on a placebo. This represented an improvement of 24.7 months (HR 0.25; 95% CI, 0.18-0.35; P<0.0001).7

Lynparza patients also did better on another measure i.e. PFS2 or time to second progression or death (HR 0.50; 95% CI 0.34-0.72; P=0.0002; median not reached vs 18.4 months) as compared to placebo.7

The most common side effects associated with Lynparza were nausea, fatigue/asthenia, vomiting, anemia, neutropenia, and thrombocytopenia.7 These safety results with Lynparza tablets were found comparable to the currently approved capsule formulation.

The results of this trial are thought to be encouraging as they build upon previous trials evaluating Lynparza in platinum-sensitive relapsed BRCA-mutated ovarian cancer. Patients are able to maintain quality of life while experiencing a delay in disease progression and this point is of particular benefit in women whose cancer is difficult to treat.7

Credit: Dr. Neha on behalf of Borderless Access

Copyright © 2017 BorderlessAccess

References

  1. World Cancer Research Fund International. Ovarian cancer statistics.
  2. American Cancer Society. What are the key statistics about ovarian cancer?
  3. Risch HA, McLaughlin JR, Cole DE, et al. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada.
  4. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy.
  5. Ashworth A. A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair.
  6. LYNPARZA™ approved by the US Food and Drug Administration for the treatment of advanced ovarian cancer in patients with germline BRCA-mutations.
  7. Lynparza Phase III SOLO-2 data demonstrate progression-free survival benefit in BRCA-mutated ovarian cancer as maintenance therapy.

 

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