Olaparib Shows PFS Benefit at 5-Year Follow-Up in BRCA Ovarian Cancer

José Baselga, MD

Patients with newly diagnosed, advanced BRCA-mutated ovarian cancer who experienced complete or partial response following platinum-based chemotherapy continued to exhibit benefit in progression-free survival (PFS) when receiving olaparib (Lynparza) at long-term follow up versus placebo as first-line maintenance, according to a press release from AstraZeneca.1

With 5-year follow-up, the SOLO-1 trial [NCT01844986] has the longest follow-up analysis for any PARP inhibitor used in as first-line maintenance.

“Once a patient’s ovarian cancer recurs, it historically has been incurable,” José Baselga, MD, PhD, executive vice president of Oncology Research & Development, said in a statement. “Even at an advanced stage, we have shown that maintenance treatment with Lynparza can help patients achieve sustained remission. [These] results further underline the critical importance of identifying a patient’s biomarker status at the time of diagnosis to offer a treatment that may help delay disease progression.”

On this phase 3, double-blind, placebo controlled, multicenter trial of olaparib, patients had a median PFS of 56.0 months compared with 13.8 months on placebo at 5 years. Olaparib reduced the risk of disease progression or death by 67% (HR, 33%; 95% CI, 0.25-0.43). There were 48.3% of patients who did not have disease progression when receiving olaparib versus 20.5% for patients receiving placebo.

There was a median recurrence-free survival was not reached by the time of this follow-up versus a median of 15.3 with placebo (HR, 0.37; 95% CI, 0.27-0.52). There was a median duration of treatment of 24.6-month with the PARP inhibitor compared with 13.9 months with placebo.

For olaparib, PFS went from 87.7% at 1 year, 73.6% at 2 years, 60.1% at 3 years, 52.3% at 4 years, to 48.3% at 5 years versus 51.4%, 34.6%, 26.9%, 21.5%, and 20.5% with placebo, respectively. The recurrence-free survival at years 1 through 5 for olaparib were 91.0%, 77.2%, 64.0%, 55.2%, and 51.9% compared with 58.0%, 39.0%, 28.9% 23.0%, and 21.8% for placebo.

Olaparib’s toxicity profile consisted of nausea in 77% of patients, fatigue/asthenia in 63%, vomiting in 40%, anemia in 39%, and diarrhea in 34% as the most common adverse events. The most common grade 3 and above events were anemia in 22% and neutropenia in 9% of patients. There were 12% of patients who discontinued treatment with olaparib due to an adverse event.

“For patients with newly diagnosed BRCA-mutated advanced ovarian cancer, the benefit derived from 2 years of maintenance treatment with Lynparza continued long after treatment ended,” Susana Banerjee, MBBS, MA, PhD, an investigator from the SOLO-1 trial and consultant medical oncologist at The Royal Marsden NHS Foundation Trust and Reader at The Institute of Cancer Research, London, said in a press release.

“After five years, almost half of women were free of cancer progression. These results represent a significant step forward in the treatment of BRCA-mutated advanced ovarian cancer,” she continued in her statement.

Olaparib was approved in the United States and multiple other countries after SOLO-1 met its primary end point in 2018.2

For the 391 patients on the trial randomized 2:1 to olaparib, treatment was given at 300 mg twice a day as maintenance monotherapy after they had received a platinum-based therapy in the front line. Treatment with olaparib or placebo was given for up to 2 years or until disease progression, and patients who had partial response at 2 years were allowed to stay on therapy at the investigator’s discretion.

“This is the first trial of a PARP inhibitor to read out a five year follow up and showed Lynparza improved PFS to over 4 and half years versus 13.8 months with placebo following response to 1st-line platinum-based chemotherapy. This latest data represents a major and significant milestone in a disease which has historically had such a poor prognosis,” Roy Baynes, MD, PhD, the senior vice president and head of Global Clinical Development, and chief medical officer at MSD Research Laboratories, said in a press release.

_Reference:

_{1. Lynparza improved median time patients lived without disease progression to over four and half years in BRCA-mutated advanced ovarian cancer vs. just over one year with placebo. News release. AstraZeneca. Published September 18, 2020. Accessed September 18, 2020. https://bit.ly/2RB9cfA}

_{2. FDA approves olaparib plus bevacizumab as maintenance treatment for ovarian, fallopian tube, or primary peritoneal cancers. FDA. Updated May 11, 2020. Accessed September 18, 2020. https://bit.ly/3hH0ffm}