Medline ® Abstracts for References 3-5
of 'Systemic treatment of metastatic breast cancer in women: Chemotherapy'
The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer.
Chia SK, Speers CH, D'yachkova Y, Kang A, Malfair-Taylor S, Barnett J, Coldman A, Gelmon KA, O'reilly SE, Olivotto IA
BACKGROUND: Over the past decade, a number of new therapeutic agents have become available in the treatment of metastatic breast cancer (MBC). This study characterized the use and assessed the impact on survival of population-based access to new agents for the treatment of MBC.
METHODS: The dates of release in British Columbia of 7 new systemic agents for MBC during the 1990s were used to construct 4 time cohorts. All patients with a first diagnosis of distant metastases in each of the time cohorts were identified and characterized, and their survival was compared. Cox proportional regression modeling was used to assess for predictors of survival.
RESULTS: In total, 2150 patients with a first distant metastases diagnosed during 1 of the 4 cohort intervals were identified. Baseline characteristics between cohorts were similar, except a greater proportion of the later cohorts received adjuvant chemotherapy (P<.001), had positive estrogen receptor status (P = .01), and had a longer median time from initial diagnosis to MBC (P<.001). Survival in Cohort 1 (1991-1992) and Cohort 2 (1994-1995; median, 438 days and 450 days, respectively) was similar. Survival was longer in Cohort 3 (1997-1998; median, 564 days; P = .002) and improved further in Cohort 4 (1999-2001; median, 667 days; P = .05). In multivariate analysis, the later cohorts were associated independently with improved survival (P = .01 and P<.001, respectively).
CONCLUSIONS: Population-based access to new therapeutic agents for MBC appeared to be associated with improved survival. To the authors' knowledge, this is the first study to date that demonstrates, from a population-based perspective, improving survival over the past decade for women with MBC.
Division of Medical Oncology, British Columbia Cancer Agency and the University of British Columbia, Vancouver and Victoria, British Columbia, Canada. firstname.lastname@example.org
Survival of metastatic breast carcinoma patients over a 20-year period: a retrospective analysis based on individual patient data from six consecutive studies.
Gennari A, Conte P, Rosso R, Orlandini C, Bruzzi P
BACKGROUND: The expectation of improvement in patient survival with administration of new chemotherapy agents for metastatic breast carcinoma (MBC) is not consistently supported by data from clinical trials, which are often underpowered and have not detected moderate survival advantage. The aim of this study was to evaluate the impact of new agents on prognosis of MBC patients enrolled in clinical trials of first-line chemotherapy.
METHODS: Between 1983 and 2001, 640 MBC patients were entered into 6 consecutive trials; the present analysis was limited to patients. The date of diagnosis of metastatic breast disease was used to define 5 arbitrarily chosen 3-year time cohorts, 1983-1986, 1987-1989, 1992-1994, 1995-1997, and 1998-2001. Multivariate proportion of hazard (PH) models were used to evaluate changes in overall survival (OS) and progression-free survival (PFS) over time and to detect changes associated with the use of taxanes, while adjusting for differences in baseline factors among 5 cohorts.
RESULTS: Patient characteristics were evenlydistributed across the 5 cohorts. Median OS was 18 months, 17.2 months, 19.2 months, 26.1 months, and 23.6 months, respectively, in cohorts 1983-1986, 1987-1989, 1992-1994, 1995-1997, 1998-2001 (P<0.0001). Age, performance status, relapse-free survival, type of adjuvant treatment, metastatic site, and taxane first-line chemotherapy were all associated with survival. These data failed to provide an indication of temporal trend and suggested a reduction in hazard of death in two cohorts (1995-1997 and 1998-2001) where taxane was added to first-line chemotherapy.
CONCLUSIONS: The analysis provided evidence of improvement in prognosis of MBC patients that was associated with use of modern chemotherapeutic agents independent of time.
Department of Oncology, Division of Medical Oncology, Santa Chiara University Hospital, Pisa, Italy. email@example.com
Fifteen-year trends in metastatic breast cancer survival in Greece.
Dafni U, Grimani I, Xyrafas A, Eleftheraki AG, Fountzilas G
Breast Cancer Res Treat. 2010;119(3):621.
In the metastatic setting, a detected time trend to improved prognosis could be attributed to the corresponding recent advances in the therapeutic approaches. The aim of the current study was to first assess, in a large cohort of well over a thousand patients, the time trends in survival in MBC for the last 15 years and second to explore its association to prognostic factors affecting outcome including therapeutic regimen. This meta-analysis uses individual patient data collected from all the trials on MBC (6 nonrandomized, 4 randomized) conducted by HeCOG from 1991 through 2006. Four 4-year time periods (1991-1994, 1995-1998, 1999-2002, and 2003-2006) were constructed for exploration of time trends in survival according to the patient's date of metastatic diagnosis. Different first line regimens in the 10 trials include anthracycline monotherapy (epirubicin, in the early 1990s) and taxane containing regimens either as monotherapy or in different combinations with anthracyclines or other drugs. In two phase II studies and in the last randomized study, trastuzumab was administered in all the patients with HER2 overexpressing tumors. In this study, information is based on a total of 1361 patients with a median follow up of 3.7 years and median survival of 1.9 years (median survival 1.28, 1.68, 2.20, and 2.57 years for 1991-1994, 1995-1998, 1999-2002, and 2003-2006, respectively). Survival improved significantly across diagnosis time periods, by 25, 44, and 51%, respectively, in each time period (1995-1998: HR = 0.75, P = 0.004; 1999-2002: HR = 0.56, P\0.001; 2003-2006: HR = 0.49, P\0.001) as compared to the first time period (1991-1994). The effect of metastatic diagnosis time period remains almost unchanged in the presence of the following significant prognostic factors: performance status, hormonal receptor status, previous adjuvant chemotherapy, previous adjuvant hormonal treatment, visceral metastasis at entry, and number of metastatic sites. When exploring the effect of new systemic treatment introduction, taking into account the same significant prognostic factors, the effect of diagnosis time period disappears, and the survival improvement is explained directly by the introduction of new agents (hormonal treatment for metastatic disease: yes vs. no: HR = 0.72, P\0.001; taxanes at first line: yes vs. no: HR = 0.69, P = 0.002; trastuzumab at first line: yes vs. no: HR = 0.63, P\0.001). The results of this study provide significant evidence of improvement in prognosis of MBC patients within the last 15 years, taking into account all the important significant prognostic factors, and this improvement can be attributed to the use of new systemic treatment agents in the management of the disease.
Laboratory of Biostatistics, Department of Nursing, School of Health Sciences, University of Athens, Papadiamantopoulou 123, Athens 11527, Greece. firstname.lastname@example.org