Overview: FDA Approval of Olaparib Maintenance for BRCA-Mutated

July 15, 2019
Naveed Saleh, MD, MS
Naveed Saleh, MD, MS

,
Mehmet Sitki Copur, MD
Mehmet Sitki Copur, MD

Volume 33, Issue 7

The US Food and Drug Administration recently approved a new indication for olaparib for maintenance treatment in adult patients with germline or somatic BRCA-mutated advanced epithelial ovarian cancer.

The US Food and Drug Administration (FDA) recently approved a new indication for olaparib (Lynparza) for maintenance treatment in adult patients with germline or somatic BRCA-mutated advanced epithelial ovarian cancer.[1] Important information about new and previous ovarian cancer indications for olaparib is detailed here.

New Indication as Maintenance Treatment

FDA approval of olaparib maintenance treatment on December 19, 2018, was supported by results from the SOLO-1 trial (NCT01844986), a randomized, double-blind, placebo-controlled trial spanning several centers. SOLO-1 examined the efficacy of olaparib vs placebo in subjects with BRCA-mutated advanced epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy.

In the trial, patients were randomized in a 2:1 ratio to receive olaparib tablets 300 mg po bid (n = 260) or placebo (n = 131). In total, 388 patients exhibited a centrally confirmed germline BRCA1/2 mutation, with 2 patients exhibiting a centrally confirmed somatic BRCA1/2 mutation. The primary endpoint was progression-free survival (PFS) assessed by investigators. Substantial improvement in PFS was demonstrated with olaparib vs placebo.[1]

After a median follow-up of 41 months, the risk of disease progression or death was 70% less with olaparib vs placebo. The estimated median PFS was not met in the olaparib arm and was 13.8 months in the placebo arm (hazard ratio [HR], 0.30; 95% CI, 0.23–0.41; P < .001). In total, 60% of women taking olaparib did not experience cancer growth or return vs 27% of women taking placebo. Of note, overall survival data were not yet realized in the study.

PFS2, a secondary endpoint defined as time from randomization to a second progression event, was a median of 41.9 months with placebo and, once again, not yet met with olaparib (HR, 0.50; 95% CI, 0.35–0.72; P < .001).

Adverse events secondary to the drug were usually low-grade. The most common adverse effects were nausea, fatigue, abdominal pain, vomiting, and anemia, among others. Recommended dosage is 300 mg po bid (total, 600 mg/d), with or without food.[2]

Importantly, the FDA also approved the BRACAnalysis CDx test (Myriad Genetic Laboratories, Inc.), a companion diagnostic tool used to isolate patients with germline BRCA-mutated advanced epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who are eligible for olaparib. The effectiveness of the tool was based on the SOLO-1 trial population for whom deleterious or suspected deleterious germline BRCA-mutated status was confirmed using prospective or retrospective testing with the BRACAnalysis CDx test.[1]

Other Indications for Ovarian Cancer

On August 17, 2017, the FDA approved olaparib tablets for the maintenance treatment of adult patients with recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.[3] In 2014, they had approved the capsule form of the drug for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been administered 3 or more prior lines of chemotherapy.

FDA approval stemmed from the randomized, placebo-controlled, double-blind trials spanning many centers, SOLO-2 (NCT01874353) and Study 19 (NCT007553545), which involved patients with recurrent ovarian cancers who responded to platinum-based therapy.

In SOLO-2, 295 patients with recurrent germline BRCA-mutated ovarian cancer, fallopian tube cancer, or primary peritoneal cancer were randomized in a 2:1 ratio to receive olaparib 300 mg po bid or placebo. The PFS as assessed by investigators showed a significant boost in those subjects taking olaparib vs placebo (HR, 0.30; 95% CI, 0.22–0.41; P < .0001). Estimated PFS was 19.1 months in the olaparib group and 5.5 months in the placebo group.[3]

Another notable finding of the SOLO-2 study was that after 2 years of taking olaparib, 43% of women did not experience disease progression vs 15% of women who took placebo.[4]

In Study 19, 265 patients with platinum-sensitive recurrent ovarian cancer-plus or minus BRCA mutations-were assessed. A total of 136 patients were administered 400 mg olaparib bid and 129 patients were administered placebo bid. Results of Study 19 indicated that patients receiving olaparib vs placebo experienced a significant increase in PFS as assessed by investigators (HR, 0.35; 95% CI, 0.25–0.49; P < .0001). The approximate median PFS was 8.4 months in those taking olaparib and 4.8 months in those taking placebo.

Finally, in both studies, adverse reactions were limited and similar to those seen in SOLO-1. Similarly, the recommended olaparib dosage for both maintenance therapy and next-line treatment is 300 mg po bid, taken with or without food.[3]

Financial Disclosure:The author and reviewer have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

References:

1. FDA. FDA approved olaparib (LYNPARZA, AstraZeneca Pharmaceuticals LP) for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based. Available at: https://www.fda.gov/drugs/fda-approved-olaparib-lynparza-astrazeneca-pharmaceuticals-lp-maintenance-treatment-adult-patients. Accessed June 27, 2019.

2. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379:2495-505.

3. FDA. FDA approves olaparib tablets for maintenance treatment in ovarian cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-olaparib-tablets-maintenance-treatment-ovarian-cancer. Accessed June 27, 2019.

4. Lynparza results. Available at: https://www.lynparza.com/ovarian-cancer/ovarian-cancer-treatment.html. Accessed June 27, 2019.

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