LISBON, Portugal-Adjuvant platinum-based chemotherapy significantly improves the outlook for women with high-risk early-stage epithelial ovarian cancer, according to the findings of two parallel, randomized phase III trials presented at the 11th European Cancer Conference (ECCO abstract 1019).
LISBON, PortugalAdjuvant platinum-based chemotherapy significantly improves the outlook for women with high-risk early-stage epithelial ovarian cancer, according to the findings of two parallel, randomized phase III trials presented at the 11th European Cancer Conference (ECCO abstract 1019).
The first International Collaboration on Ovarian Neoplasms (ICON-1) trial was carried out under the joint auspices of the UK Medical Research Council, the Mario Negri Institute for Pharmacological Research, and the Swiss Institute for Applied Cancer Research. The Adjuvant Clinical Trial in Ovarian Neoplasms (ACTION) study was sponsored by the European Organization for Research and Treatment of Cancer (EORTC).
The goal of both trials was to compare the impact on survival of initiating adjuvant chemotherapy after surgical resection vs delaying chemotherapy until relapse.
Speaking on behalf of the ICON-1 and ACTION investigators, coordinator Chris Williams, MD, explained that ICON-1, with 477 participants, was designed as a pragmatic study that was open to any patient whose physician was uncertain about whether to institute adjuvant chemotherapy.
In contrast, ACTION, which included 448 patients, was more restrictive, enrolling only those women with FIGO stage Ia or Ib and grade 2 or 3 disease, or stage Ic or IIa and any grade disease, or clear cell tumors. "There was more diversity and heterogeneity in the ICON-1 study because of the requirement of more careful selection and staging in the ACTION study," Dr. Williams noted.
More Than 90% Were Stage I
The total of 925 patients, whose median age was 55 years, were recruited at 124 centers in 13 countries over the course of nearly a decade. "It’s worth noting that more than 90% of patients had FIGO stage I disease," Dr. Williams said.
Histologic cell type was classified as serous in 34% of enrollees, mucinous in 20%, endometriod in 25%, and clear cell in 14%. Nearly one third of patients had poorly differentiated disease, 46% had intermediate differentiation, and 22% had well-differentiated disease.
In ICON-1, 82% of women received single-agent carboplatin (Paraplatin), while the rest received cisplatin (Platinol) monotherapy or combination therapy with either cisplatin or carboplatin. ACTION used combination therapy with cisplatin in 47% of patients and single-agent carboplatin in 33%. Overall, nearly 60% of patients received single-agent carboplatin and nearly 30% received combination cisplatin.
For both study populations combined, adjuvant chemotherapy increased relapse-free survival at 5 years from 65% to 76% (hazard ratio 0.64, P = .001). At 5-year follow-up, 82% of women who were treated with adjuvant chemotherapy were still alive, compared with 75% of those who received delayed chemotherapy (hazard ratio 0.68, P = .01). Thus, the absolute disease-free survival benefit for adjuvant chemotherapy was 11% and the overall survival benefit was 7%.
"These data proved for the first time that chemotherapy is effective in early ovarian cancer," Dr. Williams said. He emphasized that the advantage of chemotherapy was consistent in both studies and for all patient subgroups, irrespective of patient age, disease stage, histologic type, or grade.