Table 10

Adjuvant bone-modifying agents

StudyTrial nameSettingPrimary outcomeMedian follow-upDFS control (%)DFS gain (%)DFS HR*OS controlOS gain (%)OS HR*ESMO-MCBS V.1.1Reference
Clodronate vs placeboNSABP-B34Adjuvant clodronateDFS90.7 monthsNANil0.91 (0.78–1.07)NANil0.84 (0.65–1.05)NEB88
Ibandronate vs placeboGAINHR+ Node+DFS38.7 monthsNANil0.94 (0.77–1.16)NANil0.96 (0.71–1.31)NEB89
Denosumab vs placeboABCSG-18Postmenopausal women on AITime-to-first clinical fractureNANANANASNA90
Clodronate vs placeboAdjuvant clodronateAdjuvant clodronateTime-to-first bone metastases5.6 yearsNANANA79.3%3.60.77 (0.56–1.00) NSNEB91 92
Zoledronate vs placeboABCSG-12Premenopausal with OFSDFS94.4 months853.400.77 (0.60–0.99)94.5%2.20.66 (0.43–1.02)NEB64 71 72
Zoledronate vs placeboAZURE/BIG01-04DFS (all patients)84 monthsNA0.94 (0.82–1.06)NA0.93 (0.81–1.07)NEB93 94
Zoledronate vs placeboAZURE/BIG01-04DFS
5 years+menopausal at diagnosis
NA0.77 (0.63–0.96)NA0.81 (0.63–1.04)NEB93 94
Adjuvant bisphosphonate (meta-analysis)EBCTCGWith hormonal therapyDFS and OS5.6 yearsAllBreast cancer mortality 18.4%1.80.91 (0.83–0.99)C60
Adjuvant bisphosphonate (meta-analysis)EBCTCGWith hormonal therapyDFS and OS5.6 yearsAll-cause mortality 22.3%1.50.92 (0.85–1.00) p=0.06NEB60
Adjuvant bisphosphonate (meta-analysis)EBCTCGWith hormonal therapyDFS and OS5.6 yearsPostmenopausalBreast cancer mortality 18%3.30.82 (0.73–0.93)B60
Adjuvant bisphosphonates (meta-analysis)EBCTCGWith hormonal therapyDFS and OS5.6 woman yearsPremenopausalBreast cancer mortality 20.7%−0.1NEB60
  • Chart blanks—relevant variables not available in manuscript.

  • *HR values in parentheses refer to 95% CI.

  • AI, aromatase inhibitors; DFS, disease-free survival; ESMO-MCBS, The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale; HR+, hormone receptor-positive; NA, not applicable; NEB, No evaluable benefit; Node+, node-positive; NS, not statistically significant; OFS, ovarian function suppression; OS, overall survival; SNA, scoring not applicable.