High-dose chemotherapy with autologous stem-cell support versus standard-dose chemotherapy: meta-analysis of individual patient data from 6 randomized metastatic breast cancer trials.

Abstract

#6113 Background: The role of high-dose chemotherapy (HDC) with autologous hematopoietic stem-cell transplantation for metastatic breast cancer has not been well defined. The statistical power of the available trials has limited precision for determining whether HDC has any benefit for this indication, or for any subset of patients.
 Methods: Individual patient data from the 6 known randomized trials were merged into a single database. The primary endpoint was overall survival (OS): time from randomization to death. The secondary endpoint was progression-free survival (PFS). Cox proportional hazards regression compared the effect of HDC vs standard-dose chemotherapy (SDC) on PFS and OS adjusted for age, trial and hormone receptor (HmR) status (positive if either estrogen (ER) or progesterone (PgR) receptor positive), and other variables. Among the subset analyses considered were by age, HmR status, number metastatic sites, and soft tissue metastases.
 Results: A total of 846 patients (433 HDC, 413 SDC) had median follow-up of 1.9 years. Median age was 47 years (range 23 to 65). Preliminary analyses show that after adjusting for age and trial, HDC significantly prolonged OS (hazard ratio (HR) 0.86; 95%CI 0.73-1.00; p=0.05) and PFS (HR 0.73; 95%CI 0.63-0.84; p<0.0001). Mean improvement (out to 8 yrs) was 4 months for both OS and PFS. Both age (p=0.023) and soft tissue disease (p=0.0025) had statistically significant interactions with treatment for OS, but neither remain significant after adjusting for multiple comparisons.
 Conclusions: HDC may have a modest benefit on OS that may be greater in patients younger than 50 years. However, we were not able to draw firm conclusions about age or other subset analyses.
 
 Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6113.

Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015

“…The role of auto-HSCT for primary BC at high risk of recurrence (at least four involved axillary lymph nodes) has been assessed by several randomized trials, 167 recently evaluated by a meta-analysis of individual patient data. 168 Overall, it was shown that high-dose therapy prolonged disease-free survival when used as adjuvant therapy, and showed a benefit on BC-specific survival and OS in selected cohorts of patients. 169,170 Whether auto-HSCT has benefit in the context of contemporary taxane-based regimens and targeted therapies is largely unknown.…”

Improvement of survival and prospect of cure in patients with metastatic breast cancer

“…One trial, the PEGASE 04 study, showed a significant benefit in terms of both progression-free survival and overall survival (Table 8) [96]. In 2008, Berry et al [101] presented the first meta-analysis using individual data from six of the eight trials; this analysis showed a significant benefit in terms of progression-free survival and a trend toward benefit in terms of overall survival. Subgroup analysis suggested that young patients (less than 50 years old) and patients with only soft tissue involvement will benefit from this treatment.…”

Intensified Chemotherapy with Stem Cell Support for Solid Tumors in Adults: 30 Years of Investigations Can Provide Some Clear Answers?

“…When looking at prospective randomized studies An equivalent or better EFS has been shown in all trials but, only one published as full report could demonstrate an OS advantage (11). A recent metaanalysis of phase III studies failed to demonstrate a survival advantage of HDC in MBC (23). Also for MBC it would be important to identify pts, if any, that are likely to benefit most from HDC.…”