TOPOTECAN AND PLDH FOR ADVANCED OVARIAN CANCER

Topotecan, pegylated liposomal doxorubicin hydrochloride and paclitaxel for second-line or subsequent treatment of advanced ovarian cancer: a systematic review and economic evaluation

Background

The aim of this project was to examine the clinical effectiveness and cost-effectiveness of intravenous formulations of topotecan monotherapy, pegylated liposomal doxorubicin hydrochloride (PLDH) monotherapy and paclitaxel used alone or in combination with a platinum-based compound for the second-line or subsequent treatment of advanced ovarian cancer.

Findings

For participants with platinum-resistant disease there was a low probability of response to treatment with PLDH, topotecan or paclitaxel. Furthermore, there was little difference between the three comparators in relation to overall survival. The comparators did, however, differ considerably in their toxicity profiles. Given the low survival times and response rates, it appears that the maintenance of quality of life and the control of symptoms and toxicity are paramount in this patient group. As the three comparators differed significantly in terms of their toxicity profiles, patient and physician choice is also an important element that should be addressed when decisions are made regarding second-line therapy. It can also be suggested that this group of patients may benefit from being included in further clinical trials of new drugs.

For participants with platinum-sensitive disease there was a considerable range of median survival times observed across the trials. The most favourable survival times and response rates were observed for paclitaxel and platinum combination therapy. This suggests that treatment with combination therapy may be more beneficial than treatment with a single-agent chemotherapeutic regimen. In terms of single-agent compounds, the evidence suggests that PLDH is more effective than topotecan. Evidence from a further trial that compared PLDH and paclitaxel suggests that there is no significant difference between these two comparators in this trial. The three comparators did, however, differ significantly in terms of their toxicity profiles across the trials. Although treatment with PLDH may therefore be more beneficial than that with topotecan, patient and physician choice as to the potential toxicities associated with each of the comparators and the patient’s ability and willingness to tolerate these are of importance. Assuming the NHS is willing to pay up to £20,000–40,000 per additional QALY, PLDH appears to be cost-effective compared with topotecan and paclitaxel monotherapy, in terms of the overall patient population and the main subgroups considered.

The cost-effectiveness results for the base-case analysis were sensitive to the inclusion of additional trial data. Incorporating the results of additional trial data gave less favourable estimates for the ICER for PLDH versus paclitaxel monotherapy, compared with the base-case results. Although the ICER of PLDH compared with paclitaxel monotherapy was less favourable, PLDH was still cost-effective compared with topotecan and paclitaxel monotherapy. For platinum-sensitive patients, the combination of paclitaxel and platinum appears to be cost-effective. On the strength of the evidence reviewed here, it can be suggested that participants with platinum-resistant disease may benefit from being included in further clinical trials of new drugs. To assess the effectiveness of combination therapy against a single-agent non-platinum-based compound, it can be suggested that a trial that compared paclitaxel in combination with a platinum-based therapy versus single-agent PLDH would be a reasonable option.

Conducted by: Main C1, Bojke L2, Griffin S2, Norman G1, Barbieri M3, Mather L1, Stark D4, Palmer S2, Riemsma R1

1. Centre for Reviews and Dissemination; 2. Centre for Health Economics, University of York; 3. Economic and Health Research Centre, Universitat Pompeu Fabra, Barcelona, Department of Oncology, Bradford Royal Infirmary, UK

Further details

Project page on HTA Programme website

Related guidance

Commissioned to inform NICE Technology Appraisal 45: Topotecan, pegylated liposomal doxorubicin hydrochloride and paclitaxel for the treatment of advanced ovarian cancer (review of TA28, TA45 and TA55 (for relapsed disease only)). London: National Institute for Clinical Excellence; 2002. NB: This guidance is replaced by TA91 Ovarian cancer (advanced) - paclitaxel, pegylated liposomal doxorubicin hydrochloride and topotecan (review).

Publications

Main C, Bojke L, Griffin S, Norman G, Barbieri M, Mather L, Stark D, Palmer S, Riemsma R. Topotecan, pegylated liposomal doxorubicin hydrochloride and paclitaxel for second-line or subsequent treatment of advanced ovarian cancer: a systematic review and economic evaluation. Health Technol Assess. 2006;10(9):1-173

Funding

Commissioned by the HTA Programme on behalf of NICE's Technology Assessment Report (TAR) process