Annals of Oncology Advance Access published online on November 15, 2007
Annals of Oncology, doi:10.1093/annonc/mdm527
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© 2007 European Society for Medical Oncology
Survival outcome and cost-effectiveness with docetaxel and paclitaxel in patients with metastatic breast cancer: a population-based evaluation
1 Provincial Systemic Therapy Program
2 Centre for the Southern Interior
3 Breast Cancer Outcomes Unit, BC Cancer Agency, Vancouver
4 Breast Cancer Outcomes Unit, BC Cancer Agency and University of British Columbia, Victoria, British Columbia, Canada
* Correspondence to: Dr M. L. de Lemos, Provincial Systemic Therapy Program, BC Cancer Agency, Vancouver, British Columbia, Canada. Tel: +1-604-877-6098; Fax: +1-604-708-2024; E-mail: mdelemos{at}bccancer.bc.ca
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Abstract |
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 Top Abstract introductionpatients and methodsresultsdiscussionAcknowledgementsReferences |
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Background: A randomized controlled trial showed longer overall survival (OS) with docetaxel compared with paclitaxel in metastatic breast cancer patients with prior exposure to anthracycline. We report a similar comparison using population-based data.
Methods: Data on patients treated with single-agent paclitaxel or docetaxel were retrospectively reviewed. OS was compared using a two-tailed log-rank test and expressed as Kaplan–Meier plots. A cost-effectiveness analysis was carried out using cost/patient and OS.
Results: Four hundred and thirty-five patients met eligibility criteria. Prognostic factors were balanced between docetaxel and paclitaxel groups. Median OS was significantly longer for docetaxel versus paclitaxel [10.9 versus 8.3 months; hazard ratio 0.76; 95% confidence interval (CI), 0.62–0.92; P = 0.006]. The median number of cycles administered were four (docetaxel) and three (paclitaxel). The incremental cost-effectiveness ratio was $2434/per month of median survival gained. In the sensitivity analysis, the results were robust except that paclitaxel dominated when the low end of the 95% CI of survival for docetaxel was compared with the high end for paclitaxel.
Conclusion: This population-based study corroborated the randomized trial's conclusion that for patients with metastatic breast cancer, docetaxel provided superior survival compared with paclitaxel. Each additional month of survival had an incremental cost of $2434.
breast neoplasms, docetaxel, paclitaxel, taxoids, treatment outcome
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introduction |
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TopAbstractintroductionpatients and methodsresultsdiscussionAcknowledgementsReferences |
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In North America, breast cancer remains the most frequently diagnosed cancer in women, with an estimated 235 120 new cases being diagnosed in 2006 in the United States [1] and Canada [2], and is second only to lung cancer as the leading cause of cancer-related death, with
46 270 deaths [1, 3]. In a recent analysis, 30% of patients initially diagnosed with early stages of breast cancer develop recurrent, advanced or metastatic disease [4]. Metastatic breast cancer (MBC) is not curable with current therapy. Systemic therapy may, however, provide a modest increase in survival and palliation in most patients with MBC [5]. Many patients with MBC have previously been exposed to adjuvant anthracyclines (doxorubicin and epirubicin) and receive taxane-based therapy (paclitaxel and docetaxel) for their MBC.
Despite the increased number of active agents (e.g. capecitabine, vinorelbine and gemcitabine), single-agent taxane therapy remains one of the standard treatments for MBC [6]. Paclitaxel and docetaxel share similar chemical structures and antitumor activities but differ in non-hematologic toxicity profiles. Recently, a randomized controlled study showed that single-agent docetaxel provided superior survival to paclitaxel for patients with MBC [7]. The incidence of treatment-related toxic effects, however, was also greater with docetaxel. Since patients recruited to clinical trials often have better performance status, we compared the overall survival (OS) in patients treated with single-agent paclitaxel or docetaxel for MBC in a pragmatic population-based setting.
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patients and methods |
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TopAbstractintroductionpatients and methodsresultsdiscussionAcknowledgementsReferences |
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This was a population-based, retrospective analysis of OS and cost-effectiveness associated with paclitaxel (Taxol®; Bristol-Myers Squibb, Montréal, Québec; Paclitaxel for Injection, Biolyse Pharma Corporation, St. Catharines, Ontario) and docetaxel (Taxotere®; Sanofi-Aventis, Laval, Québec) in MBC. The study was approved by the University of British Columbia and British Columbia (BC) Cancer Agency Research Ethics Board and was supported by a research grant from the Canadian College of Clinical Pharmacy.
study population
Cases were identified from the provincial cancer registry, breast cancer outcomes unit and systemic therapy drug database of the BC Cancer Agency. The BC Cancer Agency has the mandate for cancer control in the province of BC, Canada. The BC Cancer Agency manages the budget for all the cancer drug therapy delivered to 27 000 patients annually via four regional centers and 50 community hospitals in the province of BC.
Patients were eligible for this study if they were
- treated with single-agent paclitaxel starting at 175 mg/m2 i.v. (3-h infusion) every 3 weeks or docetaxel starting at 100 mg/m2 i.v. (1-h infusion) every 3 weeks for MBC after failure of anthracycline-based chemotherapy,
- given the first dose of paclitaxel or docetaxel from 1 January 1999 and 31 December 2002 and
- treated at regional centers of the BC Cancer Agency.
study outcomes
The primary outcome was OS, defined as the time from initiation of paclitaxel or docetaxel therapy to death by any cause. Median survival was estimated using the Kaplan–Meier method. The null hypothesis was that there was no difference in survival between patients treated with paclitaxel versus docetaxel. On the basis of a baseline survival of 12 months in the paclitaxel arm [7], 450 patients were needed to detect a 50% increase in the median survival, using a two-tailed log-rank test at 
= 0.05 with 80% power.
Cost-effectiveness analysis was undertaken using the BC Cancer Agency perspective. Costs included drug, labor and supplies and were calculated using a previously described costing template [8, 9]. Since therapies were given for <1 year, costs were not discounted. Incremental cost-effectiveness ratios were on the basis of mean cost/patient and median OS for the two taxanes. For the sensitivity analyses, cost was varied to the extremes of the range of cycles. Effectiveness was varied to the extremes of the 95% confidence interval (CI) for the median OS determined in the study. Mean life expectancy was also estimated from study data by calculating the difference in area under the survival function curves [10, 11].
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results |
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TopAbstractintroductionpatients and methodsresultsdiscussionAcknowledgementsReferences |
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A total of 435 patients from four regional centers met the eligibility criteria. The paclitaxel and docetaxel groups were generally similar in age and sites of metastasis (Table 1). Slightly more patients in the docetaxel group had estrogen receptor-negative disease. The median, mean and range of the number of cycles administered were higher in the docetaxel (4, 4.3; range 1–18) group than in the paclitaxel group (3, 3.5; range 1–9).
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overall survival
The risk for death by any cause was significantly reduced in patients in the docetaxel group than in the paclitaxel group (hazard ratio 0.76; 95% CI 0.62–0.92; P = 0.006), with a corresponding prolongation of median OS (docetaxel 10.9 months 95% CI 9.19–12.62 versus paclitaxel 8.3 months 95% CI 7.04–9.65) (Figure 1).
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cost analysis
The respective monthly cost of median OS was CDN$865 (docetaxel) and CDN$353 (paclitaxel) (Table 2). The incremental cost-effectiveness ratio (ICER) of docetaxel versus paclitaxel was CDN$30 337 per life-year gained (LYG). The range of ICERs in the sensitivity analysis varying effect was CDN$13 972–CDN$91 724 per LYG (Table 3). These results were robust except that paclitaxel dominated when the low end of the 95% CI of median OS for docetaxel was compared with the high end for paclitaxel. When cost was varied, ICERs ranged from dominant to $1 80 005. The ICER for mean cost per mean life expectancy calculated at 5 years was CDN$20 919 per LYG.
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discussion |
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TopAbstractintroductionpatients and methodsresultsdiscussionAcknowledgementsReferences |
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We found that docetaxel use was associated with longer OS than when paclitaxel was used for MBC. Each additional month of median OS (life-month gained) had an incremental cost of CDN$2528 which corresponds to CDN$30 337 per median OS LYG and CDN$20 919 per LYG using a mean life expectancy method.
This is the first population-based confirmation of the phase III trial by Jones et al. [7] showing the superiority of docetaxel over paclitaxel in anthracycline-pretreated MBC. Greater toxic effects were associated with docetaxel in the clinical trial. The difference in global quality-of-life (QoL) score was not statistically significant, although the study was not powered to detect such a difference. We did not have access to prospectively collected data on toxicity or QoL in our population but it is reassuring that our findings indicate improved survival is achievable outside the clinical trial setting. The magnitude of survival gain in our study (2.6 months MOS and 3.7 months life expectancy) was similar to that seen in the clinical trial (2.7 months MOS and 4.1 months life expectancy) [7], although the OS in both arms was shorter in our study (paclitaxel 8.3 versus 12.7 months, docetaxel 10.9 versus 15.4 months). Similarly, patients received more cycles of docetaxel than paclitaxel in our study (four versus three) than in the clinical trial (six versus four) [7].
Other evidence supporting improved survival with docetaxel has been borne out by the results of a review of a population database. Chia et al. [12] reported that the cohort of MBC patients for the years 1997–1998, reflecting the introduction of docetaxel, had a longer median OS versus the years 1994–1995, corresponding to when paclitaxel was first used in the province of BC, Canada. The speed and extent of widespread use of these agents after they were introduced into the funded drug formulary in the province, however, remain unclear. Also, substantial changes in care delivery during the same periods might have contributed to improved survival (e.g. restructuring of the BC Cancer Agency in mid-1990s) [13].
There is no single standard chemotherapy regimen for patients with MBC. In addition to the taxanes, various agents (e.g. capecitabine, gemcitabine and vinorelbine) used alone or in combination have emerged to be efficacious. Three-weekly single-agent paclitaxel or docetaxel, however, remain two of the few regimens with mature data from randomized trials showing improved survival, with the exception of trastuzumab-based regimens in HER2-positive MBC. For example, Seidman et al. [14] reported improved response rate and time to progression (TtP) with paclitaxel given weekly compared with three-weekly regimen. To date, this has only been presented as an abstract [14]. Similarly, preliminary analysis reported that adding gemcitabine to paclitaxel was superior to paclitaxel alone in prolonging TtP but the effect on OS requires further follow-up [15]. Finally, weekly docetaxel has shown promising efficacy but to date this has been shown only in small uncontrolled trials [16, 17].
To compensate for the limitations of a retrospective study, we chose the robust end point of OS as our primary outcome. Nevertheless, survival rates are the products of complex processes involving the effectiveness of drug therapy and other factors which are difficult to ascertain retrospectively. These include the completeness of follow-up of patients who might have moved from BC and subsequently died and improved supportive care over the indexed periods. The absence of QoL assessment is another weakness of the present study.
Together with the findings by Jones et al. [7], our data indicate that docetaxel is more effective than paclitaxel and this superiority can be realized in the real-life practice setting at a cost of CDN$30 337 per MOS LYG and CDN$20 919 per mean LYG. It will be interesting if similar confirmation can be obtained for other commonly used chemotherapy regimens in MBC.
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Acknowledgements |
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Presented in part at the Annual Meeting of the American Society of Clinical Oncology, Atlanta, Georgia, USA, June 2006. Conflicts of interest: none declared.
Received for publication August 23, 2007. Accepted for publication October 11, 2007.
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References |
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1. Jemal A, Siegel R, Ward E, et al. Cancer statistics. 2006. CA Cancer J Clin (2006) 56(2):106–130.
2. Canadian Cancer Society/National Cancer Institute of Canada. Canadian Cancer Statistics 2006 (2006) Toronto, Canada: Canadian Cancer Society/National Cancer Institute of Canada.
3. World Health, Organization. WHO Mortality Database. http://www3.who.int/whosis/mort/table1_process.cfm (2 March 2005, date last accessed).
4. Jatoi I, Tsimelzon A, Weiss H, et al. Hazard rates of recurrence following diagnosis of primary breast cancer. Breast Cancer Res Treat (2005) 89(2):173–178.[CrossRef][Web of Science][Medline]
5. O'Shaughnessy J. Extending survival with chemotherapy in metastatic breast cancer. Oncologist (2005) 10(Suppl 3):20–29.
6. NCCN Breast Cancer Panel. The NCCN Breast Cancer Clinical Practice Guidelines in Oncology (Version 2.2006). ©2006 National Comprehensive Cancer Network, Inc. http://www.nccn.org (12 December 2006, date last accessed).
7. Jones SE, Erban J, Overmoyer B, et al. Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol (2005) 23(24):5542–5551.
8. Taylor SCM. Development of a pharmacoeconomics service in a provincial oncology program. Eur J Cancer (1997) 33(9 Suppl):S31. (Abstr PP45).[Medline]
9. Taylor SCM, Uyeno KT, O'Reilly SE, et al. Development of a systemic therapy costing model in a provincial oncology centre. Eur J Cancer (2000) 36(Suppl 3):S26. (Abstr PP64).[CrossRef][Web of Science]
10. Naimark D, Naglie G, Detsky AS. The meaning of life expectancy: what is a clinically significant gain? J Gen Intern Med (1994) 9(12):702–707.[Web of Science][Medline]
11. Tappenden P, Chilcott J, Ward S, et al. Methodological issues in the economic analysis of cancer treatments. Eur J Cancer (2006) 42(17):2867–2875.[CrossRef][Web of Science][Medline]
12. Chia S, Speers C, Kang A, et al. The impact of new chemotherapeutic and hormonal agents on the survival of women with metastatic breast cancer (MBC) in a population-based cohort. Proc Am Soc Clin Oncol (2003) 22:6. (Abstr 22).
13. Carlow DR. The British Columbia Cancer Agency: a comprehensive and integrated system of cancer control. Hosp Q (2000) 3(3):31–45.[Medline]
14. Seidman AD, Berry D, Cirrincione C, et al. CALGB 9840: phase III study of weekly (W) paclitaxel (P) via 1-hour(h) infusion versus standard (S) 3h infusion every third week in the treatment of metastatic breast cancer (MBC), with trastuzumab (T) for HER2 positive MBC and randomized for T in HER2 normal MBC [Meeting Abstracts]. J Clin Oncol (2004) 22(Suppl 14):512.
15. Albain KS, Nag S, Calderillo-Ruiz G, et al. Global phase III study of gemcitabine plus paclitaxel (GT) vs. paclitaxel (T) as frontline therapy for metastatic breast cancer (MBC): first report of overall survival [Meeting Abstracts]. J Clin Oncol (2004) 22(Suppl 14):510.
16. Burstein HJ, Manola J, Younger J, et al. Docetaxel administered on a weekly basis for metastatic breast cancer. J Clin Oncol (2000) 18(6):1212–1219.
17. Perez EA, Vogel CL, Irwin DH, et al. Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol (2001) 19(22):4216–4223.
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