Abstract 238P
Background
The results of the global BOLERO-2 trial established the efficacy and safety of combination everolimus (EVE, an mTOR inhibitor) and exemestane (EXE) in the treatment of ER+, HER2-, locally advanced, recurrent, or metastatic breast cancer (ABC). BOLERO-5 investigated this combination in Chinese post-menopausal women with ER+, HER2- ABC, refractory to letrozole or anastrozole (NCT03312738).
Methods
BOLERO-5 is a randomized, double-blind, placebo controlled, phase II trial comparing EVE (10 mg qd) or placebo (PBO) in combination with EXE (25 mg qd). The primary endpoint was PFS per investigator assessment. Key secondary endpoints included PFS per blinded independent review committee (BIRC), overall response rate (ORR), clinical benefit rate (CBR), and safety.
Results
A total of 159 patients were randomized to EVE + EXE (n = 80) or PBO + EXE (n = 79). By investigator assessment, treatment with EVE + EXE prolonged median PFS by 5.4 months (HR 0.52; 90% CI, 0.38, 0.71), from 2.0 months (PBO + EXE; 90% CI, 1.9, 3.6) to 7.4 months (EVE + EXE; 90% CI, 5.5, 9.0). Similar results were observed following BIRC assessment, with median PFS prolonged by 4.3 months (HR 0.46; 90% CI, 0.32, 0.67). Treatment with EVE + EXE improved ORR (8.8% [90% CI, 4.2, 15.8] vs 1.3% [90% CI, 0.1, 5.9]) and CBR (35.0% [90% CI, 26.1, 44.7] vs 16.5% [90% CI, 10.0, 24.9]). No new safety signals were identified in BOLERO-5, with the incidence of treatment-related adverse events in Chinese patients consistent with the safety profile of both drugs (Table). Non-infectious pneumonitis, associated with mTOR inhibitors, was reported in 5 patients (6.3%) randomized to EVE + EXE and was treatment-related. On-treatment deaths (EVE + EXE, n = 3; PBO + EXE, n = 2) were all attributed to the underlying malignancy. Table: 238P
Most frequent treatment-related AEs (reported in >20% of patients)
| EVE + EXEN = 80 | PBO + EXEN = 79 | |||
| All grades n (%) | Grade ≥3 n (%) | All grades n (%) | Grade ≥3 n (%) | |
| ≥1 Treatment-related AE | 79 (98.8) | 36 (45.0) | 46 (58.2) | 9 (11.4) |
| Hyperglycemia* | 34 (42.5) | 8 (10.0) | 2 (2.5) | 0 |
| Aspartate aminotransferase increased* | 32 (40.0) | 1 (1.3) | 11 (13.9) | 1 (1.3) |
| Stomatitis* | 27 (33.8) | 6 (7.5) | 5 (6.3) | 1 (1.3) |
| Alanine aminotransferase increased* | 23 (28.8) | 1 (1.3) | 9 (11.4) | 1 (1.3) |
| Anemia | 19 (23.8) | 3 (3.8) | 8 (10.1) | 3 (3.8) |
| Hypercholesterolemia* | 19 (23.8) | 0 | 0 | 0 |
| Mouth ulceration* | 19 (23.8) | 0 | 2 (2.5) | 0 |
| Weight decreased* | 17 (21.3) | 1 (1.3) | 2 (2.5) | 0 |
*AE occurs in a greater proportion of patients randomised to EVE + EXE (≥15% difference vs PBO + EXE)
Conclusions
The efficacy and safety results of BOLERO-5 validate the findings from BOLERO-2, and further support the use of EVE + EXE in Chinese post-menopausal women with ER+, HER2- ABC.
Clinical trial identification
NCT03312738.
Editorial acknowledgement
The authors would like to acknoweldge Mary-Clare Cathcart, PhD, of Novartis Ireland Ltd for medical writing support.
Legal entity responsible for the study
Novartis Pharma AG.
Funding
Novartis Pharma AG.
Disclosure
K. Amin, K. Slimane, Y. Qiao, Y. Liu: Financial Interests, Personal, Full or part-time Employment: Novartis. All other authors have declared no conflicts of interest.