CHICAGO – Hormonal maintenance therapy after primary treatment was associated with significantly prolonged progression-free survival when compared with surveillance in a retrospective study of women with stage II-IV low-grade serous carcinoma of the ovary or peritoneum.
The findings are “potentially practice-changing,” Dr. David Marc Gershenson of the University of Texas MD Anderson Cancer Center, Houston, said at the annual meeting of the American Society of Clinical Oncology.
Of 204 women with newly diagnosed low-grade serous carcinoma (LGSC) who underwent primary cytoreductive surgery followed by platinum-based chemotherapy, 70 received hormonal maintenance therapy after completion of primary chemotherapy and 134 underwent surveillance. Median progression-free survival (PFS) was 64.9 vs. 27.3 months, respectively (33 months overall), Dr. Gershenson said.
“To date, 40% of the hormone maintenance therapy group has not relapsed, compared [with] only 12% in the surveillance group,” he said.
Median overall survival was not statistically different, but there was a trend toward an overall survival benefit in the hormonal maintenance therapy group (115.7 vs. 98.8 months). In a subset analysis in women who were clinically disease free at the completion of primary chemotherapy, the median PFS was 29.9 months in 121 women undergoing surveillance, vs. 81.1 months in 27 receiving hormone maintenance therapy. The mean overall survival was also statistically different in the subset analysis (106.8 vs. 191.3 months).
On multivariable analysis, four factors reached significance: hormone maintenance therapy vs. surveillance (hazard ratio, 0.23), peritoneum vs. ovary as primary site (HR, 0.45), no gross residual disease vs. gross residual disease (HR, 0.49),and persistent disease at completion of chemotherapy, vs. no evidence of disease (HR, 0.42).
Patients included in the study presented between 1981 and 2013. They had a median age of 47.6 years, about 3/4 had primary ovarian LGSC, and about 1/4 had primary peritoneal LGSC.
Patients in the hormonal therapy group were treated with letrozole (54%), tamoxifen (29%), anastrozole (3%), leuprolide acetate (7%), depot medroxyprogesterone acetate (1%), and leuprolide acetate + tamoxifen or letrozole (3% each). Median duration of hormonal maintenance therapy was 33.3 months (range of 1-223), and follow-up was at least 2 years in those who had not recurred.
LGSC is a rare subtype that accounts for about 10% of serous carcinomas of the ovary or peritoneum. These cancers may arise de novo or after a diagnosis of serous borderline tumor. LGSC, relative to high-grade serous carcinoma (HGSC), is characterized by younger age at diagnosis, chemoresistance, prolonged overall survival, and aberrations within the MAP kinase signaling pathway, Dr. Gershenson said.
The findings are of interest as primary postoperative platinum-based chemotherapy remains the standard for women with newly diagnosed metastatic ovarian or peritoneal LGSC despite multiple reports indicating that this subtype is relatively chemoresistant. For example, in the AGO database of 5,114 patients accrued to four separate phase III trials, the response rate to chemotherapy in women with suboptimally debulked LGSC was significantly lower than in women with suboptimally debulked HGSC (23% vs. 90%), he said.
However, no prospective clinical trials have been conducted in the front line setting in women with LGSC, he noted.
Recent reports of promising activity of hormonal therapy in the recurrent setting have led to an increase in interest in integrating the modality into the primary treatment setting. One study showed a high frequency of ER and PR expression in LGSC, and another showed that hormonal therapy for recurrent LGSC was associated with an objective response rate of 9%, stable disease rate of 66% and median progression-free survival of 7.4 months.
“Some patients derived several years of benefit,” he said. “In addition, low-grade serous carcinoma bears a striking resemblance to luminal breast cancer in that women who are 35 years of age or younger appear to have a significantly worse prognosis.”
Some have concluded, based on these findings, that platinum-based chemotherapy is of no value in the frontline treatment of LGSC and should be abandoned, Dr. Gershenson said.
The current findings, though limited by factors such as their retrospective nature, missing data, a long study period, and possible referral bias suggest that hormonal maintenance therapy deserves a closer look, Dr. Gershenson said.
“The findings of this hypotheses-generating study are potentially practice changing and warrant further investigation using a prospective trial design,” he concluded.
Dr. Gershenson reported stock ownership in AbbVie, Biogen Idec, Celgene, GlaxoSmithKline, Johnson & Johnson, Merck, and Pfizer; consulting or advisory roles with Clovis Oncology, and patents with Elsevier and UpToDate.