Combination versus sequential single agent chemotherapy for metastatic breast cancer

Area of Science:

• Oncology
• Clinical Pharmacology

Background:

• Combination chemotherapy may enhance tumor cell kill but can compromise dose intensity and increase toxicity.
• Sequential single agent chemotherapy might allow for greater dose intensity and potentially better outcomes with less toxicity, but its impact on survival is unclear.

Purpose of the Study:

• To compare the efficacy and safety of combination chemotherapy versus sequential single agent chemotherapy in women with metastatic breast cancer.

Main Methods:

• A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing combination chemotherapy with sequential single agent chemotherapy.
• Searches conducted in major databases and clinical trial registries up to October 2013.
• Data extraction focused on overall survival, progression-free survival, tumor response, toxicity, and quality of life.

Main Results:

• Twelve RCTs (2317 patients) were included; most had high risk of bias.
• No significant difference in overall survival between combination and sequential chemotherapy (HR 1.04; P=0.45).
• Sequential chemotherapy showed improved progression-free survival (HR 1.16; P=0.01), while combination chemotherapy had higher response rates (RR 1.13; P=0.008) and increased risk of febrile neutropenia (RR 1.32; P=0.01).

Conclusions:

• Sequential single agent chemotherapy positively impacts progression-free survival in metastatic breast cancer.
• Combination chemotherapy yields higher response rates but also a greater risk of febrile neutropenia.
• No difference in overall survival exists between the two strategies, supporting sequential monotherapy use unless disease progression is rapid.