Prolonging chemotherapy until disease progression improves progression free and overall survival in metastatic breast cancer: results of a systematic review

Publication date: May 19, 2010
Category: Breast cancer, advanced
Publisher: ESMO
Authors: A. Gennari; O. Nanni; M. Puntoni; M. Sormani; M. D'Amico; D. Amadori; A. Decensi; P. Bruzzi 

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BACKGROUND: Metastatic breast cancer (MBC) is an incurable disease: the aims of therapy are palliative and include prolongation of survival with good quality of life and symptom control. In this setting chemotherapy (CT) is still considered the mainstay of any therapeutic strategy and toxicity and quality of life are important factors when deciding on drugs and schedules. In particular, the optimal CT duration is still undefined and the number of administered cycles is dictated by the tolerability profile of individual drugs. In the past 30 years a number of randomised clinical trials explored the impact of different CT duration in MBC, with inconsistent results. We have performed this metaanalysis to evaluate the impact of first line CT duration in terms of PFS and OS.

METHODS: Randomised studies, comparing shorter with longer CT duration were identified by literature search. Pooled estimates of the PFS HRs and OS HRs were obtained, according to standard meta-analysis procedures. Meta-regression analysis were performed to examine whether the overall effect on PFS was associated with time of randomization (before induction or after induction CT), number of cycles in the control arm (<6 vs >6) and co-administration of endocrine therapy.

RESULTS: Eleven eligible studies, including 2269 patients were identified and retrieved. Data on PFS and OS were available for all trials. Overall longer CT duration was associated with a 34% reduction in the hazard of progression (HR 0.66, CI 0.61-0.72; p < 0.0001) and with an 8% reduction in the hazard of death (HR 0.92, CI 0.84-0.99; p 0.04).

Meta-regression analysis showed that the magnitude of this effect was remarkably similar across groups of trials, in terms of PFS and OS, suggesting its independence of time of randomization (p = 0.91), study design (p = 0.2), number of cycles in the control arm (p = 0.6), and endocrine therapy (p = 0.6).

Conclusions: Prolonging first line CT until disease progression is a associated with a significant improvement in PFS and OS.

 

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