medwireNews: Bone-only (BO) metastatic breast cancer might have a distinct natural history to that of breast cancer with metastases affecting other organs with or without skeletal disease, research suggests.
The study pooled data for 10,521 patients taking part in 13 trials of metastatic breast cancer therapies such as palbociclib, bevacizumab, pertuzumab and lapatinib, explain Suparna Wedam and colleagues from the US Food and Drug Administration in Silver Spring, Maryland.
Half (49.0%) of the participants had bone metastases, including 12.5% of whom had metastases affecting only bone. But the proportion of patients with BO metastases ranged from 4.0% of patients with triple-negative tumours to around 15.0% of those with hormone receptor-positive/HER2-negative disease depending on prior treatment.
Using investigator-assessed outcomes, the team determined that BO metastases patients had significantly better progression-free survival (PFS) than both those with metastases affecting bone and other tissues (hazard ratio [HR]= 0.64) and those without bone metastases (HR=0.70). This was also true for overall survival, with corresponding HRs of 0.56 and 0.68.
“It is not surprising that BO [metastatic breast cancer] carries a potentially improved prognosis, given that organ function would not be affected”, the researchers comment in the Journal of Clinical Oncology.
“However, it is possible that the BO subset may respond differently to different types of therapies, given the natural history”, they suggest. “Trials looking at sequencing of therapy and potential de-escalation of therapy are merited.”
The investigators also examined the consistency of PFS when measured by local investigators and a blinded independent central review (BICR), using data from 6305 patients of nine trials.
The early discordance rate (EDR) – defined as the proportion of cases where the investigator called a progression event before the BICR – was higher for patients with BO disease than those with bone and other metastases or those with no bone metastases, at 63.2% versus 45.3% and 37.9%, respectively.
By contrast, the late discordance rate (LDR), when the investigators called progression at a later point than the BICR, was lowest for the BO patients, at 26.9% versus 40.0% and 47.6%, respectively.
These patterns were consistent when looking at subgroups of patients receiving hormone receptor- or HER2-positive agents or chemotherapy, say Suparna Wedam et al.
“It is important to note that the EDR and LDR rates only use individuals about whom there is disagreement, and that the BO subgroup has the lowest rate of overall disagreement”, the researchers
explain, but they believe that where disagreement exists in BO patients, “the local investigator tends to call the event earlier.”
Reflecting that this possible bias might be due to difficulties in assessing bone metastases, the authors summarise: “Ultimately, there seems to be an inherent difference in how the BO subgroup and the other two subgroups are assessed using RECIST.”
The investigators suggest that research into the impact of treatment on BO patients might be directed at the use of bone biomarkers or perhaps patient-reported outcomes focusing on bone pain.
“Further efforts are warranted to describe the appropriate imaging modalities and end points to better describe response to therapy and standardize bone radiographic evaluation for breast cancer clinical trials and clinical practice”, they add.
Wedam SB, Beaver JA, Amiri-Kordestani L, et al. US Food and Drug Administration pooled analysis to assess the impact of bone-only metastatic breast cancer on clinical trial outcomes and radiographic assessments. J Clin Oncol; Advance online publication 9 March 2018.
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