Capecitabine differentially helpful based on HR status

Breast cancer

By Mardi Chapman

27 May 2021

[Editor’s note: Due to a technical glitch, some readers may not have been able to access this article when it was first published on 27 May. We now republish it in full.]

A Cochrane review of the evidence has confirmed capecitabine has a moderate benefit in hormone receptor‐positive metastatic breast cancer but found no benefit in any hormone receptor subgroups in the neoadjuvant therapy.

The systematic review of 12 metastatic studies comprising 4,325 participants found a small improvement in progression‐free survival (PFS) was seen for all people (HR 0.89).

This was largely accounted for by a moderate improvement in PFS hormone receptor‐positive cancers (HR 0.82) compared to no difference in PFS for hormone receptor‐negative cancers (HR 0.96).

In six neoadjuvant trials comprising 3,152 patients, no difference in pathological complete response (pCR) was observed for either hormone receptor‐positive (OR 1.22), or hormone receptor‐negative tumours (OR 1.28).

In eight adjuvant trials comprising 13,457 patients, overall survival was no different in hormone receptor-positive patients (OR 0.86) but improved in hormone receptor-negative cancers (HR 0.72).

The review, co-authored by Associate Professor Andrew Redfern from the Fiona Stanley Hospital and the University of WA, said their findings supported other retrospective analyses that capecitabine had superior efficacy in HR+ metastatic breast cancer

“Overall, capecitabine as a single agent had comparable efficacy to other single agents, and so is a reasonable choice for all subtypes in this setting due to a relatively favourable toxicity profile.”

“Differential sensitivity of relevance to clinical practice was again observed in the adjuvant setting, albeit in the reverse direction.”

“Although no significant benefit was observed for capecitabine inclusion in the hormone receptor‐positive population, we identified statistically and clinically significant disease‐free survival and overall survival benefits for the addition of capecitabine to docetaxel, when given sequentially either before or after an anthracycline‐based component, in hormone receptor‐negative or triple‐negative breast cancer. Capecitabine inclusion should therefore be considered, at least in high‐risk triple‐negative cases, after surgery.”

They said differential activity of capecitabine between hormone receptor‐positive and ‐negative cancers in micro‐metastatic and macro‐metastatic settings could provide an opportunity to better understand the differential biology between these settings.

“Future studies should stratify by hormone receptor and triple‐negative breast cancer (TNBC) status to clarify the differential effects of capecitabine in these subgroups across all treatment scenarios, to optimally guide capecitabine inclusion,” it concluded.

Associate Professor Andrew Redfern told the limbic about 75% of patients with metastatic disease receive capecitabine at some stage.

“Where it isn’t used when it could be is for triple negative breast cancers who have an op first, The review shows that if capecitabine is combined with taxanes in the adjuvant chemo there is a strong survival advantage.”

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