Ovarian cancer is the second most common gynaecological malignancy, and is the leading cause of gynaecological cancer-related death in Europe and US. The majority of the cases are diagnosed in advanced stage, with limited chance of cure. In fact, despite its chemosensitivity, the majority of ovarian cancer patients, including those who achieve a complete response to first line chemotherapy, will relapse and eventually die.
Despite years of research on maintenance chemotherapy, immunotherapy, or targeted agents, no major survival advantage has been produced, therefore optimal surgical cytoreduction and platinum based chemotherapy is still the standard first line therapy. In June 2010, the data from the GOG 218 study were presented at ASCO. The GOG 218 is a three arms, placebo controlled study where patients were randomly assigned to standard carboplatinum –paclitaxel alone, or carboplatinum paclitaxel plus bevacizumab, or carboplatinum-paclitaxel plus bevacizumab followed by maintenance bevacizumab. In this study, a 3.8 months of progression-free survival advantage has been observed for the maintenance bevacizumab arm. In the April issue of the Journal of Clinical Oncology, a cost-effectiveness analysis of the GOG 218 study has been published (Cohn et al). This study compared actual and estimated costs for each treatment strategy. In brief, the drug costs were estimated by using Medicare reimbursement, and included the costs of cytotoxics, bevacizumab, supportive medicines, infusion costs, as well as the cost of surgical and medical care for bowel perforation. The costs for the management of other toxicities were not included in the model. The cost-effectiveness ratio was defined as the cost per year of PFS, with ICER (incremental cost-effectiveness ratio) defined as the costs for progressions-free life-year saved. The traditional willing-to-pay threshold is less than 50.000,00 $ per life-year saved. According to the model, the ICER is around 400.000,00$ for both the chemotherapy + bevacizumab arms.
The conclusions of this study are that the addition of bevacizumab to standard first line therapy is not cost-effective. As well acknowledged by the authors, this study is based on a simplified model, and on the GOG 218 results that are available in abstract from only. Moreover, the way to approach the cost-effectiveness of a given treatment is dramatically different across countries, based on the different health systems and reimbursement programmes. Therefore, this calculation may not applied to other countries. However, this study is well representative of the new scenario we are facing, where the cost-benefit ratio of new treatments must take care not only of efficacy and tolerability, but also of economical costs. Facing every day patients with no more chance for cure, all oncologists claim with enthusiasm a study with potential benefit for the patients, and consider the costs of secondary importance. However, even if not taking costs into account, the benefit of adding bevacizumab is not so clear. In fact the progression free survival is an artificial end point which is strictly dependent on how it is measured.
In the GOG 218 study, Ca125 and instrumental assessment were repeated every three months, therefore the majority of the patients experienced an asymptomatic progression. The clinical meaning of prolonging asymptomatic progression free survival in ovarian cancer has to be demonstrated. It has been shown in a prospective randomized study that starting second line therapy on the basis of the raise of CA 125 versus waiting for symptomatic progression has no impact on survival but adversely affect patients quality of life (Rustin G, Lancet 2010). Therefore, apart from the costs, do a 3.8 months gain in PFS deserve 6 chemotherapy courses + bevacizumab followed by 51 weeks on bevacizumab?