Munich, Germany—Long-term therapy with olaparib (Lynparza), a poly (ADP ribose) polymerase (PARP) inhibitor, in women with newly diagnosed advanced ovarian cancer and a BRCA1 or BRCA2 mutation led to a significant, unprecedented improvement in progression-free survival (PFS), reducing the risk for disease progression or death by 70% compared with placebo, according to results of the phase 3 SOLO-1 clinical trial.
If longer follow-up shows improved survival, olaparib in the first-line setting for maintenance therapy will become the standard of care for patients with advanced ovarian cancer with BRCA1 or BRCA2 mutation. These results were presented at the ESMO 2018 Congress and published simultaneously in the New England Journal of Medicine.1
Olaparib in the First-Line Setting
Olaparib is currently indicated as maintenance therapy after several lines of therapy in women with ovarian cancer and a BRCA mutation. These new results highlight olaparib’s potential role as first-line treatment in this patient population.
“The results of SOLO-1 herald a new era in treatment for women diagnosed with advanced ovarian cancer who carry a BRCA1 or 2 mutation. This study demonstrates an outstanding improvement in progression-free survival over placebo, which is maintained even after olaparib is stopped at 2 years,” said lead investigator Kathleen Moore, MD, Associate Professor, Section of Gynecologic Oncology, Stephenson Cancer Center, University of Oklahoma, Oklahoma City.
“These data suggest that we have a new standard of care for women with ovarian cancer who harbor a BRCA mutation,” Dr Moore said.
“While it is too early to say whether we have impacted the fraction of newly diagnosed women who could be cured with their front-line therapy, the fact that it is estimated that over 50% of women on the olaparib arm were still progression free at 4 years as compared to only 11% for placebo speaks to this hope,” she said.
“We need ongoing follow-up to see if the benefit continues to be durable or even a cure. These results apply only to those with a BRCA1/2 mutation,” Dr Moore emphasized.
SOLO-1 Study Details
The SOLO-1 study included 391 patients with high-grade serous or endometrioid ovarian cancer and BRCA1 or BRCA2 mutation in clinical complete response or partial response after platinum-based chemotherapy. Participants were randomized in a 2:1 ratio to oral olaparib 300 mg twice daily (N = 260) or to matching placebo (N = 131) for 2 years or until disease progression or unacceptable toxicity. Patients who had a partial response at 2 years could continue olaparib therapy for a total of 3 years. The median duration of follow-up was approximately 41 months. At the time of analysis, the median PFS was not reached in the olaparib group and was 13.6 months in the placebo group (P <.0001).
Olaparib did not compromise the ability to benefit from a second therapy at disease progression. Among patients who received a second therapy, PFS remained significantly improved in those who received olaparib maintenance.
At 3 years, the rate of freedom from disease progression and death was 75% in the olaparib group versus 60% in the placebo group (P <.001).
Olaparib was generally well-tolerated. Adverse events were mostly low grade, and only 11.5% of patients discontinued olaparib therapy because of toxicity. Serious adverse events were reported in 21% of the olaparib group versus 12% of the placebo group. Anemia was the most common serious adverse event, reported in 7% and 0% of patients, respectively.
Health-related quality of life did not deteriorate over the course of the study in patients receiving olaparib maintenance.
Dr Moore said that when the study started, she thought patients should be able to continue to use olaparib indefinitely. “The results are reassuring that 2 years of treatment is sufficient,” she told the audience.
A New Standard of Care?
ESMO expert and study co-author Nicoletta Colombo, MD, PhD, Director, Gynecologic Cancer Medical Treatments, European Institute of Oncology, Milan, Italy, commented at a press conference, “I am extremely excited about these data. These results will change standard of care for patients with advanced ovarian cancer and a BRCA mutation.”
Other studies evaluating the use of PARP inhibitor maintenance therapy in advanced ovarian cancer include PRIMA and PAOLA-1.
- Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018 Oct 21. Epub ahead of print.