Fulvestrant, letrozole preferred for HR-positive, HER2-negative breast cancer
Fulvestrant 500 mg and letrozole may be optimal first-line endocrine monotherapy alternatives for hormone receptor (HR)-positive, HER2-negative advanced breast cancer, with favourable time to progression (TTP), progression-free survival (PFS), objective response rate (ORR), and tolerability profile, according to a meta-analysis.
Subjects were 3,492 postmenopausal women with HR-positive, HER2-negative metastatic or locally advanced breast cancer identified from eight randomized trials. Participants were assigned to receive one of the following: aromatase inhibitors (AIs, either anastrozole, exemestane, or letrozole), tamoxifen, fulvestrant 500 mg, or fulvestrant 250 mg. [Medicine (Baltimore) 2017;doi:10.1097/MD.0000000000007846]
Longer TTP/PFS was observed with fulvestrant 500 mg compared with the other agents except letrozole (hazard ratio [HR], 1.54 for anastrozole, HR, 1.61 for exemestane, HR, 1.84 for tamoxifen, and HR, 2.17 for fulvestrant 250 mg).
“Fulvestrant 500 mg may be the best option … to prolong TTP/PFS,” said the researchers, with letrozole as the second option. “Letrozole was the only therapy with no significant difference from fulvestrant 500 mg and … ranked higher in efficacy than the two other AIs.”
Compared with tamoxifen and fulvestrant 250 mg, the most effective agents in terms of ORR were letrozole (odds ratio [OR], 0.59 and OR, 0.54, respectively) followed by exemestane (OR, 0.67 and OR, 0.61).
Tamoxifen and fulvestrant 250 mg were the least effective agents in terms of both TTP/PFS and ORR as per Bayesian estimation.
All agents were well tolerated with no significant adverse events except for the hot flash incidences reported with tamoxifen use. [J Clin Oncol 2004;22:1605-1613]
Endocrine therapy is the preferred first-line treatment for HR-positive, HER2-negative postmenopausal advanced breast cancer to optimize survival time and improve quality of life. [http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed September 22, 2017; BMC Med 2015;13:46; Ann Oncol 2014;25:1871-1888] However, there is limited evidence as to which monotherapy regimen would generate optimal results, noted the researchers.
The researchers identified a class effect among the three AIs, which support their role as potential alternatives to the most widely used tamoxifen due to greater tolerability and efficacy. [J Clin Oncol 1995;13:513-529; Cochrane Database Syst Rev 2009;4:Cd003370; Br J Cancer 2004;90:20-25]
“The AIs were generally more efficacious than fulvestrant 250 mg and tamoxifen,” said the researchers, favouring letrozole over the other two AIs given the favourable outcomes for both TTP/PFS and ORR.
Overall, letrozole and fulvestrant 500 mg had the most favourable efficacy and tolerability profiles among the agents evaluated, said the researchers. However, direct comparisons among other endocrine monotherapies are still warranted to determine other probable differences among these agents. Furthermore, therapy duration and the specific disease condition should also be taken into consideration when choosing treatment options, they added.