EU Panel Backs Olaparib Approval for Frontline Maintenance in Ovarian Cancer

Gina Columbus

Dave Fredrickson

Dave Fredrickson

The European Committee for Medicinal Products for Human Use (CHMP) has recommended approval of olaparib (Lynparza) as a frontline maintenance treatment for patients with BRCA-mutant advanced high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response (PR) following first-line platinum-based chemotherapy.1

UPDATE 6/19/2019: Frontline Maintenance Olaparib Approved in Europe for Ovarian Cancer

The positive opinion is based on findings from the phase III SOLO-1 trial, in which olaparib led to a 70% reduction in the risk of disease progression or death following response to platinum-based chemotherapy compared with placebo (HR, 0.30; 95% CI, 0.23-0.41; P <.001).2,3

“There remains a significant unmet need in the treatment of advanced ovarian cancer as 70% of women, globally, relapse within the first three years after their initial treatment,” Dave Fredrickson, executive vice-president, oncology, AstraZeneca, said in a press release. “The results of SOLO-1 demonstrate the potential of using Lynparza earlier in the treatment pathway as a maintenance therapy, and they reinforce the importance of identifying a patient’s BRCA mutation status as soon as they are diagnosed.”

The FDA approved the PARP inhibitor in this setting, also based on the phase III data, in December 2018—making it the first approval for this class of agents in the frontline maintenance setting.

At the time of the FDA approval, the BRACAnalysis CDx® assay was also approved and indicated for healthcare professionals to identify patients with advanced ovarian cancer who have a germline BRCA mutation and are eligible for first-line maintenance therapy with olaparib in this setting.

In the phase III SOLO-1 trial, investigators explored maintenance olaparib following platinum-based chemotherapy in newly diagnosed patients with advanced ovarian cancer with a BRCA1/2 mutation. Patients with newly diagnosed, FIGO stage III-IV, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer with germline or somatic BRCA mutations were enrolled. These patients must have also received cytoreductive surgery and be in clinical complete response or PR after platinum-based chemotherapy.

Treatment continued until disease progression, and was stopped in patients with no evidence of disease at 2 years. However, patients with a PR at 2 years could continue therapy.

Secondary endpoints of the trial were PFS2, which is defined as time from randomization to second progression event, overall survival (OS), and quality of life.

At a median follow-up of 40.7 months, results showed that the median progression-free survival (PFS) by independent central review was not reached in the olaparib arm (n = 260), compared with 14.1 months in the placebo arm (n = 131). The investigator-assessed PFS in the olaparib arm was not reached versus 13.8 months in the placebo arm (HR, 0.30; 95% CI, 0.23-0.41; P <.0001). The median PFS for olaparib has not yet been reached.

Additionally, patients who received olaparib maintenance showed a statistically significant improvement in PFS2, with a median PFS2 not reached, compared with 41.9 months in the placebo group (HR, 0.50; 95% CI, 0.35-0.72; P = .0002). OS data are not yet mature. Regarding quality of life, there were no clinically relevant changes. The discontinuation rate in the olaparib arm was 12%.

Regarding safety, the most common adverse events (AEs; ≥20%) were nausea (77%), fatigue (64%), vomiting (40%), anemia (39%) and diarrhea (34%). Moreover, the most common grade ≥3 AEs were anemia (22%) and neutropenia (8%). A total 71% of patients on the olaparib arm remained on the recommended starting dose of 300 mg twice daily, and 88% of olaparib-treated patients continued on therapy without an AE-related discontinuation. Forty-eight percent of patients on the olaparib arm did not experience dose interruption due to an AE.

References

  1. LYNPARZA® (olaparib) Receives Positive EU CHMP Opinion for First-Line Maintenance Treatment in BRCA-Mutated Advanced Ovarian Cancer. Merck. Published April 29, 2019. https://bit.ly/2Pz8QEt. Accessed April 29, 2019.
  2. Moore K, Colombo N, Scambia G, et al. Olaparib maintenance therapy following first-line platinum-based chemotherapy in patients with FIGO stage III–IV ovarian cancer (OC) with a BRCA1/2 mutation (BRCAm): Phase III SOLO1 trial. In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract LBA7_PR.
  3. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Eng J Med. 2018;379(26):2495-2505. doi: 10.1056/NEJMoa1810858.
Printer Printing...