Lynparza Receives Additional FDA Approval for Ovarian Cancer

New tablet formulation approved as maintenance treatment regardless of BRCA status

The PARP inhibitor olaparib (Lynparza, AstraZeneca/Merck) has received FDA approval for a broader indication in ovarian cancer cases, including a new tablet formulation that will ease women’s pill burden.

The FDA approved:

  • New use of olaparib tablets as a maintenance treatment of adults with recurrent, epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy, regardless of BRCA status.
  • New use of olaparib tablets (two tablets twice daily) as opposed to capsules (eight capsules twice daily).
  • Conversion of accelerated approval to full approval for the use of olaparib in adult women with deleterious or suspected deleterious germline BRCA-mutated (gBRCA) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy; patients for this indication are selected for therapy based on an FDA-approved companion diagnostic.

The approval “demonstrates that olaparib is an effective option for maintenance therapy for certain ovarian cancer patients, regardless of BRCA status,” said Richard Penson, MD, Clinical Director of Medical Gynecologic Oncology at Massachusetts General Hospital Cancer Center, Associate Professor of Medicine at Harvard Medical School, and the primary investigator in the SOLO-2 trial.

Two randomized trials supported the new approvals and the conversion of accelerated approval to full approval, which was originally based on a single-arm trial.

SOLO-2 (N = 295) confirmed the benefit of olaparib in gBRCA-mutated patients, demonstrating a 70% reduced risk of disease progression or death (hazard ratio [HR], 0.30; 95% confidence interval [CI], 0.22–0.41; P < 0.0001) and improved median progression-free survival (PFS) to 19.1 versus 5.5 months for placebo by investigator-assessed analysis.

Study 19 (N = 265) showed that olaparib reduced the risk of disease progression or death by 65% and improved PFS compared with placebo in patients of any BRCA status (HR, 0.35; 95% CI, 0.25–0.49; P < 0.0001; median PFS of 8.4 months with olaparib versus 4.8 months with placebo). Additionally, patients in Study 19, treated with olaparib as a maintenance therapy, had a median overall survival (OS) of 29.8 months versus 27.8 months for placebo (HR, 0.73; 95% CI, 0.55–0.95).

The most common adverse reactions (20% or more) in clinical trials were anemia, nausea, fatigue (including asthenia), vomiting, nasopharyngitis/upper respiratory tract infection/influenza, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, and decreased appetite, constipation, and stomatitis. Most common laboratory abnormalities (at least 25%) were decrease in hemoglobin, increase in mean corpuscular volume, decrease in lymphocytes, decrease in leukocytes, decrease in absolute neutrophil count, increase in serum creatinine and decrease in platelets.

Lynparza was first approved under the FDA’s Accelerated Approval program in December 2014, as a capsule formulation, making it the first poly ADP-ribose polymerase (PARP) inhibitor approved. Since then, more than 3,000 advanced ovarian cancer patients have been treated with olaparib capsules. Lynparza capsules are not indicated for maintenance therapy.

To avoid substitution errors and overdose, do not substitute Lynparza tablets with Lynparza capsules on a milligram-to-milligram basis due to differences in the dosing and bioavailability of each formulation.

Source: AstraZeneca; August 17, 2017.