Adjuvant bisphosphonates in early breast cancer: consensus guidance for clinical practice from a European Panel

Abstract

Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus. The panel recommended that bisphosphonates should be considered as part of routine clinical practice for the prevention of CTIBL in all patients with a T score of <-2.0 or ≥2 clinical risk factors for fracture. Compelling evidence from a meta-analysis of trial data of >18,000 patients supports clinically significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy. Therefore, the panel recommends that bisphosphonates (either intravenous zoledronic acid or oral clodronate) are considered as part of the adjuvant breast cancer treatment in this population and the potential benefits and risks discussed with relevant patients.

Indoleamine 2,3-Dioxygenase and Its Therapeutic Inhibition in Cancer

“…Early pembrolizumab combination data indicated that the combination was well tolerated with promising clinical activity (Gangadhar et al , 2016). Among 19 treatment-naïve advanced melanoma patients, 4 CR, 7 PR, and 3 SD were reported resulting in 58% ORR and 74% DCR, with responses in all epacadostat dose cohorts ≥50 mg BID and at all target lesion sites including in liver, lung and lymph nodes.…”

“…Among 19 treatment-naïve advanced melanoma patients, 4 CR, 7 PR, and 3 SD were reported resulting in 58% ORR and 74% DCR, with responses in all epacadostat dose cohorts ≥50 mg BID and at all target lesion sites including in liver, lung and lymph nodes. All responses reported at presentation were confirmed and ongoing and median PFS had not been reached (Gangadhar et al, 2016). These results compare favorably with pembrolizumab monotherapy or nivolumab-ipilimumab combination therapy in melanoma patients (Postow et al , 2015; Robert et al , 2015).…”

Inflammatory Reprogramming with IDO1 Inhibitors: Turning Immunologically Unresponsive ‘Cold’ Tumors ‘Hot’

“…In clinical studies, epacadostat is generally well tolerated at doses of >100 mg twice daily with some evidence of cancer control [134]. Efficacy is currently being studied in several tumor types in combination with anti-PD-1 or anti-PD-L1 antibodies with early data providing evidence of favorable clinical activity [135]. …”

St. Gallen/Vienna 2017: A Brief Summary of the Consensus Discussion about Escalation and De-Escalation of Primary Breast Cancer Treatment

“…Following a recent update of the respective joint ASCO/Cancer Care Ontario Clinical Practice Guideline [10], the panel clearly defined adjuvant bone-targeted agents such as zoledronic acid q 6 months or oral clodronate during adjuvant endocrine therapy as standard of care for postmenopausal patients, aiming at the improvement of disease free survival (DFS), irrespective of bone mineral density (76% yes, 18% no, 6% abstain) [11]. The panel was less clear on the same questions for premenopausal women on ovarian function suppression (plus tamoxifen or AI) (53% yes, 37% no, 10% abstain), and voted against adjuvant bisphosphonates for young patients without LHRH agonist therapy (90% yes, 2% no, 8% abstain).…”