The agency also may have had concerns about the lapatinib study’s use of a primary end point based upon investigator assessment.
For open-label trials using progression-free survival as the primary end point, the agency generally requires 100% blinded independent review of progression determinations, although it has indicated a willingness to consider relaxing this requirement. During the afternoon session of ODAC’s July 24 meeting, the committee will discuss the feasibility of conducting independent audits of only a subgroup of patient scans in trials using this end point.
The fact that independent blinded review was not the lapatinib trial’s primary end point might have been a concern for the agency, as might related issues such as missing data or informative censoring. Furthermore, the upper limit of the 95% confidence interval for the independent review results fell just below 1.0, according to the published results, and this statistical result may not have held up under further scrutiny by agency reviewers.
Waiting on Other Studies
Although GSK said that it would await the results from other studies that will provide additional information about the combination of lapatinib with trastuzumab, it declined to highlight any one study in particular.
The ClinicalTrials.gov database lists numerous breast cancer studies, currently in recruitment, for which both lapatinib and trastuzumab are study interventions.
These include a randomized, open-label, phase III trial evaluating the efficacy and safety of lapatinib in combination with trastuzumab vs. trastuzumab alone as maintenance therapy in women with HER2-positive metastatic breast cancer. The 280-patient study, which is being conducted in the United States and Canada, is expected to complete in August 2014.
Another phase III trial is comparing the safety and efficacy of an aromatase inhibitor in combination with lapatinib, trastuzumab or both for the treatment of hormone receptor–positive, HER2-positive metastatic breast cancer. The estimated completion date for the 525-patient study is December 2017.
Editor’s note: This story appears courtesy of "The Pink Sheet," a weekly Elsevier publication covering pharmaceutical business and policy issues. To learn more, contact customer care at 800-332-2181 or sign up for a free trial.