Bone health

Spotlight on underuse of bone modifying agents in cancer patients


Many Australian HER2+ metastatic breast cancer (MBC) patients with bone metastases do not receive a bone modifying agent (BMA) and there is significant practice variation among clinicians when it comes to dosing, interval schedules and de-escalating the therapy, registry data shows.

The prospective review of patient data from the HER2+ MBC registry, TABITHA, is the first to describe Australian clinicians’ prescription of BMAs.

Denosumab appeared to be favoured over bisphosphonates and the majority of patients were initiated on a BMA at the time of bone metastases diagnosis. However, one in four patients did not receive a BMA at any point in their treatment course. In addition, there was significant variation reported in BMA treatment intervals.

Of the 171 patients who had bone metastases at diagnosis between 2015 and 2020, 76% received a BMA, with clinicians favouring denosumab (69%) over a bisphosphonate (31%).

According to investigators from the Walter and Eliza Hall Institute of Medical Research, patients who received a BMA were more likely to have bone-only metastases at metastatic breast cancer diagnosis (24% vs 7%, p=0.02) and less likely to have presence of visceral metastases (51% vs 71%, p=0.03).

But for the 24% of patients who did not receive a BMA there was a lower proportion with bone-only metastases, and a higher proportion of patients with visceral metastases.

Speaking to the limbic, oncologist Dr Vanessa Wong from Ballarat Health Services Department of Medical Oncology in Victoria said, in the context of visceral disease, the prioritisation of systemic chemotherapy or HER-2 directed therapy may be a potential explanation for this finding, with clinicians electing to withhold BMA for fear of adding complexity to the existing systemic treatments.

Other reasons for non-initiation of BMA included low volume bone metastases  or wanting to wait until first- line systemic treatment had failed.

“Now we haven’t seen that in trials – that low volume bone metastases versus high volume changes the risk of bone complications” she said, noting guidelines recommend starting BMAs from first radiological confirmation of bone metastases, regardless of the presence of symptoms. This was based on landmark BMA studies in breast cancer showing a delay in the median time to the occurrence of the first skeletal related event by almost 50%.

Meanwhile, a significant proportion of patients who did not receive a BMA also did not receive any systemic therapy (either anti-HER2 agents or chemotherapy). This was likely to reflect a cohort of patients who, whether through preference or performance status, were unsuited for systemic anticancer treatment and were treated with best supportive care (BSC) alone, she noted.

Uncertainty persists

Dr Wong said despite their high uptake, uncertainty around the optimal use of BMAs still persisted.

“I think there’s a lot of uncertainty about risk-benefit, cost effectiveness and treatment burden – should we be asking patients who are at home, not receiving active systemic therapy for their cancer, to present to hospital to receive these agents particularly because it can take three months on treatment to see an effect and they may not survive this time.”

Some patients on a BSC pathway may not survive to receive this benefit, she added, saying that further research was needed on the optimal selection of patients that will benefit most from BMA in the BSC setting.

Dr Wong also noted there was ongoing uncertainty about what to do at progression of bone metastases while patients are on a BMA.

Of the 62 patients who had disease progression in the bone, either alone or with other sites, 60% continued on the same BMA,  14% switched BMA and 31% stopped their BMA.

In comparison, of the 25 patients who had non-bone disease progression, 40% continued on the same BMA, 4% switched 56% stopped their BMA.

Those that ceased BMA use also ceased all systemic HER2 directed treatment.

“We need further research to understand why clinicians are prescribing BMAs in different intervals and we need to know what the impact of this variation is on management of bone metastases,” said Dr Wong.

The team at WEHI are now recruiting patients into a new registry for advanced HR+ breast cancer called ARORA

“We’re hoping to have more data collected specifically on bone metastases to see about clinician variance in other subtypes of breast cancer as well.”

Clinicians are encouraged to contact the team to enrol patients who have been diagnosed from January 2020 on.

Internal Medicine Journal

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