Ovarian Cancer: extended survival with hormonal maintenance therapy1 Jun 2016
Hormonal maintenance therapy (HMT) in women with stage II-IV low-grade serous carcinoma (LGSC) of the ovary or peritoneum produced a statistically significant improvement in progression-free survival compared with surveillance alone after primary platinum-based chemotherapy, researchers reported.
In a retrospective study cohort consisted of 204 patients, treated at MD Anderson during 1981-2013 for newly diagnosed stage II-IV low-grade serous carcinoma (LGSC), an indolent form that accounts only for about 10% of serous ovarian/peritoneal cancer but is more chemo resistant than its high-grade counterpart. "It affects younger women in their 40s, and even some in their 20s or teens, and it's associated with better outcomes than other ovarian cancers," said David M. Gershenson, MD, of The University of Texas MD Anderson Cancer Center, Houston. About 70% of patients will recur.
Clinical trial details
Although platinum-based primary chemotherapy remains the standard of postsurgical care, the chemo resistance of this hormone receptor-expressing subtype underlines the need for more customized alternatives. "Over the past decade it's become increasingly clear that epithelial ovarian cancer isn't one but several distinct entities, but we've been treating them identically irrespective of histological subtype. With this particular subtype the one-size-fits-all treatment strategy may not be the best approach," said Amanda N. Fader, MD, of Johns Hopkins Medicine in Baltimore.
In the MD Anderson protocol, patients had primary cytoreductive surgery followed by platinum-based chemotherapy and at least 2 years' follow-up if the cancer had not recurred. HMT, consisting of estrogen inhibition with letrozole, tamoxifen, anastrozole, or leuprolide acetate, was given to 70 women and surveillance to 134 -- both at the discretion of their physicians.
Of the eligible participants, the majority had primary ovarian LGSC, and the majority showed no clinical evidence of tumor at completion of primary chemotherapy. The primary endpoint was progression-free survival.
Increased progression-free survival with HMT
In the study median progression-free survival was 64.9 months, or 5.4 years, for women on HMT versus 27.3 months for those on surveillance. Overall survival was 115.7 months following HMT, versus 98.8 months for surveillance. "HMT was generally well tolerated and, as in breast cancer, some of these patients have been on it for several years now," Gershenson said.
In other study findings:
- 40% of HMT recipients have so far experienced no cancer recurrence versus 12% of surveillance patients.
- In an earlier analysis of this cohort, HMT patients had a significantly decreased risk of recurrence compared with those on surveillance, for a hazard ratio of 0.20.
- The benefit of HMT was greater in the 148 patients who showed no clinical evidence of disease following chemotherapy, for a progression-free survival of 81.1 versus 29.9 months (6.7 versus 2.5 years), and overall survival of 191.3 versus 106.8 months (16 versus 9 years).
- In subset analyses, women with primary peritoneal rather than ovarian disease also had better outcomes.
“This treatment approach could potentially be practice-changing"
"Based on reports of the promising activity of hormonal therapy in the recurrent setting, there is increasing interest in integrating this modality into the primary treatment setting," Gershenson wrote. Fader called the findings "quite exciting" and potentially representing "a significant advancement in our understanding of how to best treat this tumor type in the upfront setting. This is one of the studies that has shown the best progression-free survival for women with this disease."
She said that she and her colleagues have conducted a pilot study of 27 women treated after cytoreduction with HMT alone. "Preliminarily, these patients do as well as, if not better than, those treated with chemotherapy," she said, although she cautioned that effective cytoreductive surgery remains the mainstay of treatment.
"We are trying to understand how rich the hormone receptor expression these tumors needs to be in order to see a response, but there certainly is a role for studying HMT in conjunction with chemotherapy or possibly HMT by itself," Fader said.
"These results have prompted us to recommend that there be a prospective clinical trial," Gershenson said, conceding that the rarity of this cancer makes recruitment difficult. "We'll probably need three or four sites. But based on the evidence so far, this treatment approach could potentially be practice-changing."Source: MedPage Today