Role of aromatase inhibitors and Zoledronic acid ( Zometa ) as adjuvant treatment of premenopausal endocrine-responsive breast cancer patients is debated.
Letrozole ( Femara ) has never been tested in this clinical setting.
Following surgery and eventual neoadjuvant or adjuvant chemotherapy, premenopausal patients ( last menses within 1 year ) were randomly assigned 1:1:1 to Triptorelin ( Decapeptyl ) 3.75 mg every 4 weeks plus either Tamoxifen 20 mg/die ( T ), or Letrozole 2.5 mg/die ( L ) or Zoledronic acid 4mg iv every 6 months + Letrozole 2.5 mg/die ( ZL ), for 5 years.
The primary end-point was disease-free survival ( DFS ) including locoregional or distant recurrence, second breast or non-breast invasive cancer and death without cancer as event.
Analysis was based on intention-to-treatment.
From March 2004 to August 2015, 1065 patients were randomized ( T: 354, L:356, ZL: 355 ) in 16 centres in Italy.
Median age was 45; 68% had a pT1 tumor; 55% had negative nodes; 63% had received chemotherapy.
After 65 months median follow-up, there were 58, 44, and 32 DFS events and 5 years DFS probability was 0.85, 0.93 and 0.93 in the Tamoxifen, Letrozole and Letrozole - Zoledronic-acid arms, respectively ( P=0.008 ).
Pairwise comparison was statistically significant for Letrozole - Zoledronic-acid versus Tamoxifen ( hazard ratio, HR 0.52, 95% CI 0.34-0.80, P=0.003 ) but not for Letrozole versus Tamoxifen ( HR 0.72, 95% CI 0.48-1.07, P=0.06 ) and Letrozole - Zoledronic-acid versus Letrozole ( HR 0.70, 95% CI 0.44-1.12, P=0.22 ).
Letrozole - Zoledronic-acid was more effective than Tamoxifen in all subgroups, but for HER2-positive cases ( interaction P=0.002 ).
Twenty-six ( 7% ) patients with Tamoxifen, 26 ( 7% ) with Letrozole and 59 ( 17% ) with Letrozole - Zoledronic-acid stopped assigned treatment before 5 years due to toxicity or refusal.
Grade 3-4 side-effects were reported in 4%, 7% and 9% of patients with Tamoxifen, Letrozole and Letrozole - Zoledronic-acid, respectively; there were 4 cases of osteonecrosis of the jaw in the Letrozole - Zoledronic-acid arm.
In conclusion, HOBOE has shown that, in premenopausal early breast cancer patients, the Letrozole - Zoledronic-acid plus Triptorelin combination is more effective than Tamoxifen + Triptorelin in terms of disease-free survival.( Xagena )
Source: European Society of Medical Oncology - ESMO Congress, 2018