TWO-YEAR MAINTENANCE therapy with olaparib (Lynparza), a poly (ADP-ribose) polymerase inhibitor, achieved a significant improvement in progression-free survival in patients with newly diagnosed advanced ovarian cancer and a BRCA1 or BRCA2 mutation, according to results of the phase III SOLO-1 trial. At a median-follow-up of 41 months, olaparib maintenance reduced the risk of disease progression or death by 70% compared with placebo. Median progression-free survival was not reached for the olaparib-treated group vs 13.8 months for the placebo group (P < .0001).

Kathleen Moore, MD

“Median progression-free survival looks to be approximately 3 years longer with olaparib compared with the placebo group,” said lead author Kathleen Moore, MD, Associate Professor, Stephenson Cancer Center, University of Oklahoma, Oklahoma City, who presented these results at the European Society for Medical Oncology (ESMO) 2018 Congress.¹ Study results were published online in The New England Journal of Medicine to coincide with the presentation at ESMO.²

“The results of SOLO-1 herald a new era in treatment for women diagnosed with advanced ovarian cancer who carry a BRCA mutation [BRCA1 and/or BRCA2]. This study demonstrates an outstanding improvement in progression-free survival over placebo, which is maintained even after olaparib is stopped at 2 years,” Dr. Moore added. “These data suggest that we have a new standard of care for women [in this setting].”

Women with newly diagnosed ovarian cancer are currently the only patients with this disease with curative potential, she noted. “While it is too early to say whether we have impacted the fraction of 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 11% on the placebo arm) speaks to this hope,” she remarked. “We need ongoing follow-up to see if the benefit continues to be durable or even a cure.”

Nicoletta Colombo, MD

Commenting on the results, study coauthor Nicoletta Colombo, MD, of the University of Milan Bicocca, European Institute of Oncology, Milan, Italy, said, “I am extremely excited about these data. These results will change the standard of care for patients with advanced ovarian cancer and a BRCA mutation.”

Dr. Moore emphasized, however, “we can’t extrapolate these results to all comers.”

“These findings are reassuring about the safety of olaparib maintenance.”

— Kathleen Moore, MD

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Study Background

“ALTHOUGH OVARIAN cancer is highly treatable and usually chemosensitive, 10-year survival hovers at around 10% to 15% and not all of this is disease-free survival. As of now, the vast majority of patients have a disease recurrence within 3 years. They are treatable but not curable. Improvements need to come from front-line treatment,” Dr. Moore explained.

SOLO-1 is the first, double-blind, randomized, prospective phase III trial to evaluate front-line olaparib maintenance therapy after platinum-based chemotherapy in newly diagnosed patients with advanced ovarian cancer (stage III–IV) who have a BRCA mutation.

“The study provides the first large data set of prospectively collected outcomes for this population of women,” Dr. Moore said.

The study enrolled a total of 391 patients with high-grade serous or endometrioid ovarian cancer who were in clinical complete response or partial response after platinum-based chemotherapy. Participants were randomly assigned 2:1 to receive oral olaparib at 300 mg twice daily (n = 260) or matching placebo (n = 131) for 2 years or until progressive disease or toxicity. Patients in partial response at 2 years had the option of continuing olaparib for a total of 3 years.

Baseline characteristics were well balanced between the two treatment arms. The median duration of follow-up was about 41 months.

The primary endpoint was investigator-assessed progression-free survival (ie, time from randomization to objective disease progression on imaging). Secondary outcomes included progression-free survival 2 (ie, time from randomization to the second disease progression event), overall survival, and quality of life.

Key Findings

“OLAPARIB TREATMENT did not affect the chance of benefit from a second therapy at disease progression,” Dr. Moore explained. Progression-free survival 2 remained significantly improved among patients treated with olaparib maintenance. At 3 years, the rate of freedom from disease progression and death was 75% in the olaparib group vs 60% in the placebo group (P < .001).

Olaparib was well tolerated. Serious adverse events were reported in 21% of the olaparib group vs 12% of the placebo group. Adverse events were mostly low grade, and only 11.5% of patients discontinued olaparib due to toxicity. Over 70% of patients were maintained on their starting dose throughout the trial.

The investigators found no clinically relevant decrease from baseline health-related quality of life for patients assigned to olaparib therapy. “These findings are reassuring about the safety of olaparib maintenance.”

Treatment Duration

REGARDING THE duration of treatment in SOLO-1, Dr. Moore commented that at first she wanted to allow patients to remain on olaparib “forever.” However, “now that I see the data—and with 40 months of follow-up, I see the survival curve doesn’t change at 2 years—I am more comfortable stopping treatment at 2 years,” she said. “Perhaps we can stop even earlier, but that has not been shown. We need to get approval for olaparib in the front-line setting first.”

At a press conference held during the ESMO meeting, Dr. Moore commented, “This study shows the importance of clinical trials. It showed that my bias about wanting longer treatment was wrong. Results will make our patients more comfortable taking the drug for only 2 years…. We have provided convincing data that we don’t have to treat [with olaparib] indefinitely.” ■

DISCLOSURE: SOLO-1 was supported by AstraZeneca and Merck. Dr. Moore is a consultant/advisor for and has received honoraria from AstraZeneca, Advaxis, Clovis Oncology, Tesaro, Genentech/Roche, VBL Therapeutics, Immunogen, Janssen Oncology, and Aravive; has received institutional research funding from PTC Therapeutics and Lilly; and has received reimbursement for travel/accommodations/ expenses from Genentech/Roche. Dr. Colombo is a consultant/advisor/speaker, has had writing engagements and public presentations with Roche, AstraZeneca, PharmaMar, Tesaro, Clovis, Advaxis, Pfizer, Takeda, Immunogen, and Biocad; and has institutional financial interests in Roche, PharmaMar, and AstraZeneca.

REFERENCES

1. 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 with a BRCA1/2 mutation: Phase III SOLO1 trial. ESMO 2018 Congress. Abstract LBA7. Presented October 21, 2018.

2. Moore K, Colombo N, Scambia G, et al: Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. October 21, 2018 (early release online).