Plenary Poster ANZBMS-MEPSA-ANZORS 2022

Bayesian Network Meta-Analysis of Cancer Events in Trials of Osteoporosis Therapies (#205)

Alexander H Seeto 1 , Joshua Long 1 , Kevin Leow 2 , Mina Tadrous 3 , Abadi Kahsu Gebre 4 , Joshua R Lewis 4 , Howard A Fink 5 , Peter R Ebeling 6 , Alexander J Rodriguez 6
  1. Griffith University, Southport, QLD, Australia
  2. The Canberra Hospital, Canberra
  3. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto
  4. Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Joondalup
  5. Geriatric Research Education and Clinical Center, VA Health Care System, Minneapolis
  6. Bone and Muscle Health Research Group, Monash University, Clayton

Anti-resorptive drugs reduce skeletal-related events in cancer. However, little is known about the effects of these and other osteoporosis therapies on incident cancer in postmenopausal women. Therefore, we conducted a network meta-analysis (NMA) examining cancer adverse event data from randomised trials of osteoporosis therapies in postmenopausal women.

Trials were identified from recent NMAs of osteoporosis therapies for fracture reduction, updated to December 2020. Included trials enrolled >100 postmenopausal women per study without cancer at baseline, randomised to placebo or an active comparator (bisphosphonate, denosumab, parathyroid [PTH] analogue, romosozumab, or menopausal hormone therapy [MHT] such as selective estrogen receptor modulators or direct estrogen and/or progesterone supplementation), and reported primary skeletal outcomes. We extracted incident cancer diagnoses from reported trial adverse events. Outcomes of interest were breast cancer, and a composite comprising all cancer events. Data were synthesized into a random-effects model using Bayesian principles. Relative to placebo, point estimates for the odds ratio with 95% credible intervals were generated. Probabilistic ranking of treatment safety in relation to cancer diagnoses was performed.

We identified 33 eligible trials, enrolling 54,617 women. During a mean follow-up of 24 months, 85 incident breast cancer events (0.16%) and 1229 incident all cancer events (2.25%) occurred. We found no significant difference in either cancer outcome between placebo or any osteoporosis therapy. In probabilistic ranking, MHT and bisphosphonates were less likely to have increased risk of breast cancer than placebo. Denosumab, romosozumab and PTH analogues ranked more likely to have increased risk of breast cancer than placebo. Probabilistic rankings were similar when considering all cancer events.

We found no pooled direct/indirect evidence that osteoporosis therapies significantly increased the risk of cancer relative to placebo. Equally, there was no convincing evidence that osteoporosis therapies reduced cancer risk in the setting of fracture reduction in postmenopausal women.

Probablistic Ranking

6292e0b8da97a-Breast+cancer+SUCRA.jpg