Benefit Strongly Suggested With Hormonal Maintenance in Low-Grade Serous Carcinoma

A rare subtype of cancer of the ovaries/peritoneum






Women with stage II–IV low-grade serous carcinoma who received hormonal maintenance therapy following primary treatment had a significantly better outcome, compared with women who underwent surveillance. — David Marc Gershenson, MD

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In patients with low-grade serous carcinoma, maintenance hormonal therapy reduced the risk of recurrence by 77%, compared with surveillance, in a retrospective cohort from The University of Texas MD Anderson Cancer Center. The study was reported by David Marc Gershenson, MD, at the 2016 ASCO Annual Meeting.1 Dr. ­Gershenson acknowledged that, as a retrospective study conducted over a long period, the study has some limitations; however, the findings “are potentially practice-changing,” he maintained.

“Women with stage II–IV low-grade serous carcinoma who received hormonal maintenance therapy following primary treatment had a significantly better outcome, compared with women who underwent surveillance,” reported Dr. Gershenson. They had superior median progression-free survival and, for the subgroup with no evidence of disease following primary treatment, superior progression-free and overall survival. For the entire subset with no evidence of disease, median overall survival was 115.7 months (median overall survival = 106.8 months for the surveillance group and 191.3 months for the hormonal maintenance therapy group).

Rare Subtype Not Chemosensitive

Low-grade serous carcinoma is a rare subtype of cancer of the ovaries/peritoneum. It may arise de novo or following a diagnosis of serous borderline tumor. Relative to high-grade serous carcinoma, low-grade serous carcinoma is characterized by young age at diagnosis, chemoresistance, prolonged overall survival, and aberrations within the MAP kinase-signaling pathway, Dr. Gershenson shared. “There have been no prospective clinical trials in the front-line setting, but data from the MD Anderson low-grade serous carcinoma database have suggested relative chemoresistance in multiple settings,” he added.

A recent report from the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group database of 5,114 patients, for example, found that among patients with low-grade serous carcinoma who were suboptimally debulked, the response rate to platinum/taxane chemotherapy was 23%, compared with 90% for patients with high-grade serous carcinoma who were also suboptimally debulked.2 The conclusion was that low-grade serous carcinoma is not as responsive to standard chemotherapy as high-grade tumors.

Without other more active treatments, according to the 2015 Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference, “Platinum-based chemotherapy is a standard for high-risk, early or advanced-stage, rare epithelial ovarian cancers and should remain the control arm” for trials of new approaches, according to Dr. Gershenson.

Based on reports of the promising activity of hormonal therapy in the recurrent setting, there has been increasing interest in integrating this modality into the primary treatment setting. The purpose of this study was to evaluate the effect of hormonal maintenance therapy compared with surveillance after primary treatment in a retrospective cohort.

Study Details

The study included 204 patients diagnosed with stage II–IV low-grade serous carcinoma between 1981 and 2013. Patients’ median age was 47.7 years; 75% had primary ovarian low-grade serous carcinoma, and 25% had primary peritoneal low-grade serous carcinoma; 30% had no gross residual disease, and 70% had residual disease, with no differences between the arms.

Role of Hormonal Maintenance in Low-Grade Serous Tumors A long-term retrospective study of 204 patients with low-grade serous carcinoma found that hormonal therapy reduced the risk of disease progression by 77%, compared with surveillance (P < .001).

Median progression-free survival was 27.3 months with surveillance and 64.9 months with hormonal therapy (HR = 0.23; P < .001).

In patients without evidence of disease after chemotherapy, median progression-free survival was 29.9 months with surveillance and 81.1 months with maintenance therapy (P < .001), and median overall survival was 106.8 months vs 191.3 months, respectively (P = .04).

At the completion of chemotherapy, however, the groups differed in terms of disease status, with 60.9% of the hormonal maintenance group demonstrating persistent disease, compared with only 8.3% of the surveillance group, revealed Dr. Gershenson.

All patients who had not recurred had been followed for at least 2 years after primary cytoreductive surgery and platinum-based chemotherapy. Following chemotherapy, patients started on hormonal maintenance (n = 70) or underwent surveillance only (n = 134). Hormonal therapy consisted primarily of letrozole (54.3%) and tamoxifen (28.5%); in the entire cohort, 13% of patients switched to another hormonal therapy due to toxicity. The median duration of hormonal therapy was 33.3 months (range, 1–223 months).

Risk of Progression Reduced by 77%

Despite a much greater frequency of persistent disease after primary treatment, patients in the hormonal therapy maintenance group experienced significantly less disease progression, Dr. Gershenson reported. For the entire cohort of 204 women, median progression-free survival was 27.3 months in the surveillance group and 64.9 months in the hormonal therapy group, representing a 77% reduction in risk, according to the multivariate analysis (P < .001). The proportion of patients who were recurrence-free was 23% vs 40%, respectively. Median overall survival was numerically but not statistically significantly improved, from 98.8 months with surveillance to 115.7 months with maintenance (P = .36).

In patients with no evidence of disease at the completion of chemotherapy, median progression-free survival was 29.9 months with surveillance and 81.1 months with maintenance therapy (P < .001), and median overall survival was 106.8 months vs 191.3 months, respectively (P = .04). ■

Disclosure: Dr. Gershenson has consulted for Clovis Oncology and owns stock in AbbVie, Biogen Idec, Celgene, GlaxoSmithKline, Johnson & Johnson, Merck, and Pfizer.

References

1. Gershenson DM, Bodurka DC, Coleman RL, et al: Hormonal maintenance therapy for women with low grade serous carcinoma of the ovary or peritoneum. 2016 ASCO Annual Meeting. Abstract 5502. Presented June 5, 2016.

2. Grabowski JP, Harter P, Heitz F, et al: Operability and chemotherapy responsiveness in advanced low-grade serous ovarian cancer: An analysis of the AGO Study Group metadatabase. Gynecol Oncol 140:457-462, 2016.

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