Neoadjuvant olaparib feasible for women with germline-mutant ovarian cancer
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Key takeaways:
- The NOW trial demonstrated the feasibility of neoadjuvant therapy with olaparib for certain women with ovarian cancer.
- Women had favorable surgical outcomes after only two cycles of treatment.
Neoadjuvant therapy with olaparib showed feasibility for women with germline-mutant ovarian cancer, according to results of the NOW trial presented at Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.
Researchers observed favorable surgical outcomes — even among women with stage IV disease — after only two cycles of the poly(ADP-ribose) polymerase (PARP) inhibitor, which had a manageable safety profile.
“Importantly, patients were very excited about the opportunity to avoid chemotherapy if safe and effective,” Shannon N. Westin, MD, MPH, professor in the department of gynecologic oncology and reproductive medicine in the division of surgery at The University of Texas MD Anderson Cancer Center, said during a presentation.
Background and methods
Use of PARP inhibitors as maintenance therapy in front-line ovarian cancer has become standard of care, Westin said.
“As with any success in drug development, we wondered if there was an opportunity to move these agents earlier in the treatment continuum,” she said.
The single-arm, open-label, investigator-initiated NOW trial sought to determine the feasibility of the PARP inhibitor olaparib (Lynparza; AstraZeneca, Merck) in the neoadjuvant setting among women with newly diagnosed germline-mutant ovarian cancer. Secondary objectives included estimated efficacy according to RECIST version 1.1, proportion of patients able to undergo interval tumor reductive surgery, PFS, complete pathologic response rate and toxicity.
The study included 15 women (median age, 56 years; 73.3% white; 80% non-Hispanic) with stage IIIC to stage IVB disease and germline mutations in BRCA1 (n = 11) BRCA2 (n = 2) RAD51C (n = 1) or PALB2 (n = 1). The women received two, 28-day cycles of olaparib dosed at 300 mg twice daily, followed by imaging to assess response. Those deemed amenable to surgery proceeded directly to tumor reductive surgery. Those with response not amenable to surgery or disease progression proceeded to chemotherapy followed by tumor reductive surgery, if possible, Westin said.
Women received adjuvant and maintenance therapy at the discretion of the provider and patient.
Results and implications
Thirteen women (86.6%) underwent surgery immediately after olaparib therapy. One of the two women who also received chemotherapy never underwent surgery because of worsening performance status.
The 14 women who underwent surgery all had optimal tumor reduction, and 12 (85.7%) had no gross residual disease at the time of surgery. One woman had a pathologic complete response.
In an evaluation of adjuvant therapy, Westin noted what she called an interesting trend: the number of chemotherapy cycles, which started at six, decreased as the study progressed. Three patients immediately resumed olaparib therapy after surgery with no intervening chemotherapy, she said.
Twelve patients (80%) received olaparib maintenance.
Among the 13 evaluable women with measurable disease, 53.8% had a partial response, 46.2% had stable disease and none had progressive disease. Nearly three-quarters of women (73%) had at least a 75% decrease in CA125 (median best percentage change, 81%).
With median follow-up of 11.7 months, researchers estimated a 12-month PFS probability of 0.81 (95% CI, 0.42-0.95). Median PFS had not yet been reached.
No unexpected adverse events occurred. The most common toxicities included abdominal pain (33.3%), constipation (26.7%) and anemia (20%). Three women had grade 3/grade 4 anemia.
“Only one patient required a dose interruption and dose reduction for grade 3 anemia,” Westin said.
The results warrant further study to determine whether PARP inhibitors can be administered in lieu of chemotherapy in the neoadjuvant setting, according to researchers.
“Certainly many questions remain, and we’re looking forward to the opportunity to review quality-of-life data, as well as a molecular assessment including [circulating tumor DNA] and tissue biomarkers in a future meeting,” Westin said.
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Westin SN, et al. NOW: Neoadjuvant olaparib window trial in newly diagnosed BRCA-mutant ovarian cancer (late-breaking abstract). Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, Florida.
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