Author/Editor		Goldvaser, Hadar; Ribnikar, Domen; Majeed, Habeeb; Ocaña, Alberto; Amir, Eitan
Title		Absolute benefit from adjuvant chemotherapy in contemporary clinical trials
Type		članek
Vol. and No.		, št. Vol. 71
Publication year		2018
Volume		str. 68-75
ISSN		0305-7372 - Cancer treatment reviews
Language		eng
Abstract		Many adjuvant breast cancer trials have observed smaller than anticipated differences between experimental and control groups. Accurate estimation of the absolute benefits of treatment is essential for the planning of clinical trials. Methods We searched PubMed to identify contemporary randomized trials comparing different adjuvant chemotherapy regimens in breast cancer. The absolute difference in 5-year disease-free survival (DFS) and overall-survival between experimental and control groups were extracted, weighted by individual study sample size and pooled. Analyses were performed for estrogen receptor (ER) negative and ER-positive disease. Meta-regression explored the influence of patients and tumor characteristics and median follow-up on the benefit from treatment. Results Analysis included 19 studies comprising 41,564 patients. Studies comparing chemotherapy regimens of different generations showed the largest difference in 5-year DFS (+7.4% for 3rd vs. 2nd generation and +5.9% for 2nd vs. 1st generation for ER-negative disease, and +2.3% for 3rd vs. 2nd generation and +1.8% for 2nd vs. 1st generation for ER-positive disease). Studies comparing chemotherapy regimens from the same generation showed smaller differences in DFS in both subgroups. Meta-regression showed that larger tumors and nodal involvement had significant greater magnitude of effect on 5-year DFS for ER-negative, but not ER-positive disease. Age and menopausal status had no effect in either subgroup. Conclusions Absolute differences between adjuvant chemotherapy regimens of the same generation are small even in ER-negative disease. Enrichment of trials for patients with poor clinical features results in larger magnitudes of benefit from treatment at 5%years in ER-negative, but not ER-positive disease.
Keywords		rak dojke trojno negativni rak adjuvantna kemoterapija podtipi breast cancer triple negative adjuvant chemotherapy subtypes