In the 5-year follow-up of the pivotal SOLO-1 trial in women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation, maintenance treatment with olaparib led to a more than doubling in progression-free survival, according to a presentation at the Society of Gynecologic Oncology (SGO) 2021 Annual Meeting on Women’s Cancer, held virtually.¹

“The initial results were extremely positive. Now, the 5-year follow-up demonstrates a statistically significant, sustained progression-free survival benefit that is appreciated across both higher-risk and lower-risk groups,” said the study’s lead author, William H. Bradley, MD, a gynecologic oncologist at Froedert and Medical College of Wisconsin, Milwaukee.

“The 5-year follow-up demonstrates a statistically significant, sustained progression-free survival benefit that is appreciated across both higher-risk and lower-risk groups.”

— William H. Bradley, MD

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Olaparib is an oral inhibitor of poly [ADP-ribose] polymerase (PARP). SOLO-1 evaluated olaparib as a 2-year maintenance therapy in 391 women with newly diagnosed advanced ovarian cancer harboring a germline or somatic BRCA1/2 mutation who had received platinum-based therapy as their initial treatment.

Data from this 5-year follow-up are the longest for any PARP inhibitor in the setting of maintenance after primary therapy, Dr. Bradley noted.

In the current analysis, median progression-free survival for the overall population was sustained far beyond the end of treatment: 56.0 months with olaparib vs 13.8 months with placebo (hazard ratio [HR] = 0.33; 95% confidence interval [CI] = 0.25–0.43). The 5-year progression-free survival was 48% vs 21%, respectively.

“After 5 years, almost half of patients were progression-free vs 20% with placebo. This is the only PARP inhibitor for which efficacy has been demonstrated beyond the completion of therapy,” he indicated. “These results further support the use of maintenance olaparib as a standard of care for women with newly diagnosed advanced ovarian cancer and a BRCA mutation and suggest the possibility of long-term remission or even cure for some patients.”

Deborah Armstrong, MD

The study’s invited discussant, Deborah Armstrong, MD, Professor of Oncology and Director of the Breast and Ovarian Surveillance Service at Johns Hopkins Medicine, reiterated Dr. Bradley’s optimism. “Maybe we can start to use ‘the C word,’” she said. “Not cancer, but ‘cure,’ for some of these patients,” she commented.

Benefit in High-Risk and Low-Risk Patients

Additionally, the researchers analyzed subgroups of patients based on their risk of disease progression. Compared with those given placebo, olaparib recipients had better 5-year progression-free survival, regardless of their initial risk.

Higher-risk disease consisted of patients with stage IV disease, those with stage III disease who underwent initial neoadjuvant chemotherapy and interval cytoreduction, and patients with stage III gross residual disease after initial cytoreductive surgery. Lower-risk disease included patients with stage III disease who underwent optimal cytoreductive surgery and had no gross residual disease.

For the higher-risk subgroup, median progression-free survival was 40.6 months with olaparib and 11.0 months with placebo (HR = 0.35). For the lower-risk subgroup, this outcome was not reached with olaparib and was 21.9 months with placebo (HR = 0.38).

“Secondary data outcomes also support the observed benefit in progression-free survival,” he continued. The time to second disease progression or death was reduced by 54% with olaparib, and the time to subsequent therapy was reduced by 54% as well.

“Also, of note, we saw no new safety signals—including no additional cases of myelodysplastic syndrome or acute myeloid leukemia during this follow-up period,” Dr. Bradley further reported. The incidence of these secondary malignancies remained at less than 1.5%. 

DISCLOSURE: Dr. Bradley has served as a consultant or advisor to Celsion and Inovio Pharmaceuticals; and has been reimbursed for travel, accommodations, or other expenses by Clovis Oncology and Inovio. Dr. Armstrong has served as a consultant or advisor to AbbVie and Eisai; has received institutional research funding from AstraZeneca, Clovis Oncology, Eisai, Pfizer, and Syndax; and has held other relationships with AstraZeneca.

REFERENCE

1. Bradley W, Moore K, Colombo N, et al: Maintenance olaparib for patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation: 5-year follow-up from SOLO-1. Society of Gynecologic Oncology 2021 Annual Meeting on Women’s Cancer. Abstract 39. Presented March 20, 2021.