Overall, women who received HMT lived more than twice as long without disease progression compared with women who did not receive hormonal therapy after surgery. Overall survival (OS) was more than a year longer in HMT-treated patients (115.7 versus 102.7 months), reported David Gershenson, MD, of the MD Anderson Cancer Center in Houston, and colleagues.
Patients who had no evidence of disease after surgery derived even greater benefit from HMT, living 7 years longer than similar patients who entered surveillance without HMT, they wrote online in the Journal of Clinical Oncology.
Though compelling, the evidence requires validation in a prospective clinical trial before HMT becomes part of routine care for patients with low-grade serous ovarian cancer, according to Gershenson.
“Some would say that we already have enough evidence from our retrospective study to support the use of hormonal maintenance therapy, but the gold standard is always a prospective, randomized trial,” Gershenson told MedPage Today. “We’ve designed the trial. We’ve gone through several levels of approval with the National Cancer Institute, and we’re meeting with our international partners in June.”
The findings confirmed an initial report at the 2016 American Society of Clinical Oncology annual meeting.
The findings applied only to low-grade serous ovarian cancer, which accounts for about 10% of all newly diagnosed ovarian cancer. In contrast to the more common high-grade disease, low-grade serous ovarian cancer is relatively chemotherapy insensitive. The German gynecologic oncology group (AGO) recently confirmed low-grade disease’s lack of responsiveness to chemotherapy, which accelerated the search for alternatives to chemotherapy.
Similarities between low-grade serous ovarian cancer and hormone receptor-positive breast cancer have stimulated interest in hormonal treatment for the low-grade ovarian disease. A high proportion of low-grade serous cancers exhibit estrogen and progesterone receptor expression, and hormonal therapy had proved beneficial in relapsed disease.
Gershenson’s group said their experience with low-grade serous ovarian cancer led them to conclude that the disease is not completely resistant to platinum-based chemotherapy, and they continue to recommend it as adjuvant therapy following surgical debulking of stage II-IV disease. However, the authors also acknowledged that “others have begun to abandon postoperative chemotherapy in favor of hormonal therapy despite lack of data from prospective clinical trials.”
They sought to examine the benefits of postoperative HMT in a retrospective review of patients treated from 1981 to 2013. MD Anderson established a low-grade serous tumor database in 2007, and a search of patient records initially identified 544 patients. After exclusions because of incomplete data and other factors, 203 patients remained for the analysis, consisting of 133 who had surgery and adjuvant platinum-based chemotherapy followed by observation and 70 who received HMT after surgery and chemotherapy. The most commonly used agent for HMT was letrozole (Femara, 54.3%), followed by tamoxifen (28.6%).
The observation and HMT groups did not differ significantly with respect to clinical or demographic factors. The study population had a median follow-up duration of 70.8 months, 80.3 months in the observation group and 54.9 months in the HMT group. Overall, the patients had a median progression-free survival (PFS) of 32.6 months. However, HMT was associated with significant prolongation of PFS (64.9 versus 26.4 months, P<0.001).
Median OS for all 203 patients was 104 months. Although patients in the HMT group had numerically better survival, the 13-month difference did not achieve statistical significance (P=0.42).
The authors performed a separate analysis of patients who were clinically disease free after adjuvant chemotherapy (n=144). The data showed that patients in the observation group had a median PFS of 30.0 months compared with 81.1 months with HMT. Women with residual or persistent disease also benefited from HMT, reflected in a median PFS of 38.1 months versus 15.2 months with observation. Both differences represented a significant advantage for HMT (P<0.001).
Women who were clinically disease free after chemotherapy had a OS of 191.3 months if they received HMT versus 106.8 months with observation. Those who had persistent disease had a median OS of 83 months with HMT and 44.4 months without. Both differences achieved statistical significance in favor of HMT (P=0.014).
An analysis of survival by estrogen (ER) and progesterone receptor (PR) status showed that PFS was significantly longer with HMT among women who were ER-positive, PR-positive, or PR negative. OS trended in favor of HMT, but did not achieve statistical significance for any of the analyses of hormone receptor status. Only three evaluable patients were ER-negative, precluding meaningful comparisons.
Study limitations included its retrospective nature, long study period, incomplete data, potential referral bias, heterogeneous therapies, and differing follow-up practice patterns.