The latest Phase III trial data on Roche’s Avastin (bevacizumab) for treating ovarian cancer have delivered another set of encouraging results on the drug’s potential to improve progression-free survival (PFS) in this underserved indication.
The picture remains unclear, though, on overall survival (OS), a measure that will be of interest both to regulators assessing Avastin as a potential treatment for ovarian cancer and to health technology assessors who will need to grapple with the drug’s cost implications if it is approved in this setting.
In the interim analysis of overall survival from the Icon7 study with Avastin, a sub-group of patients at high risk of recurrent ovarian cancer did show a statistically significant gain in OS.
Data from two Phase III trials with Avastin in ovarian cancer were presented at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, US.
The new findings on progression-free survival came from OCEANS, a multicentre study evaluating Avastin plus chemotherapy (gemcitabine and carboplatin), followed by Avastin alone, in 484 women with platinum-sensitive recurrent ovarian, primary peritoneal or fallopian tube cancer.
The headline results from the OCEANS trial, which bolstered previously reported outcomes from US and international studies of Avastin in ovarian cancer, were that PFS after a median follow-up of 24 months was 12.4 months in women who continued on Avastin compared with 8.4 months in patients who received chemotherapy alone.
That represented a statistically significant 52% reduction in the risk of disease progressing for women given Avastin in addition to chemotherapy.
Roche also highlighted that tumour shrinkage (the objective response
rate) was 78.5% in women on the Avastin based regime compared with
57.4% in the chemotherapy-only group.
This was a secondary endpoint in OCEANS, while PFS was the primary endpoint. Also among the secondary endpoints was overall survival, where data were considered premature to date.
An early OS analysis, not mentioned by Roche, showed median survival of 29.9 months in the chemotherapy alone group versus 35.5 months in Avastin group.
“Women with recurrent ovarian cancer need new treatment options, and it is therefore an important advance to halve the risk of disease progression in this incurable cancer,” commented Dr Hal Barron, chief medical officer and head of Global Product Development at Roche.
“These data add to the growing body of evidence supporting Avastin’s potential role in this disease, which includes two previously presented phase III clinical trials in women with newly diagnosed ovarian cancer.”
Roche did not publicise either the results of the interim analysis of survival data from the ICON7 trial presented at ASCO, which showed an overall trend in favour of Avastin but did not reach statistical significance in the overall study population.
Sponsored by the UK’s Medical Research Council, the ICON7 trial involved 1,528 women at 263 study centres in Europe, Canada, Australia, and New Zealand with newly diagnosed high-risk early or advanced epithelial ovarian, primary peritoneal or fallopian tube cancer.
Roche had already presented data from ICON7 at the European Society of Medical Oncology (ESMO) meeting last October.
These suggested that chemotherapy-naïve ovarian cancer patients who received Avastin in combination with standard chemotherapy, then continued on Avastin, were around 27% more likely to live longer without the disease progressing than women on chemotherapy alone (corresponding to a 21% reduction in risk of cancer progression or death).
The company has already filed for European approval of Avastin in ovarian cancer and is in discussion with US regulators over this indication.
The interim analysis of overall survival in ICON7 presented at the ASCO meeting had been requested by regulatory authorities looking at the possibility of approving Avastin for ovarian cancer.
The analysis showed that after a median 28 months’ follow-up, 178 women had died in the Avastin group compared with 200 in the group on standard chemotherapy – a 15% reduction overall in the risk of death that was not considered statistically significant.
In a planned subgroup analysis of patients at the highest risk of their cancer recurring, though, the reduction in risk of death was a statistically significant 36% for Avastin compared with standard chemotherapy patients (79 versus 109 deaths respectively).
The final analysis of overall survival in the ICON7 trial is not expected until 2013. Despite the equivocal survival results so far, UK charity Target Ovarian Cancer picked up on the finding in the interim analysis that women in the high-risk group who took Avastin lived on average around eight months longer than those who did not.
This led Target Ovarian Cancer to renew a call for the licensing and cost-benefit assessment of Avastatin as a treatment for ovarian cancer on the National Health Service to be fast-tracked.
The eight-month survival gain also fired up the Mail On Sunday, which said Avastin had been hailed as the “biggest breakthrough in 20 years of ovarian cancer research”.
The influential newspaper neglected to mention, though, that the survival benefit related to a sub-group of high-risk patients, or that the overall improvement in survival – conspicuous by its absence – was not considered statistically significant.