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Spotlight: BioPER trial for HR+/HER- advanced breast cancer

Updated: Jun 7, 2023

For breast cancer patients that have hormone-receptor positive/HER2-negative (HR+/HER2-) advanced breast cancer, the standard first line of treatment is cyclin-dependent kinases (CDK) 4 and 6 inhibitors plus endocrine therapy [1]. However, the optimal treatment for patients who experience a progression after this treatment remains largely unknown. Preliminary findings suggest that adaptive resistance may be more frequently related to endocrine therapy rather than to the CDK4/6 inhibitor [2]. Therefore, the BioPER study explored if re-treating patients with the CDK4/6 inhibitor palbociclib but changing the endocrine therapy regimen could provide a clinical benefit [3].

BioPER was an investigator-initiated, multicenter, single-arm, open-label, phase II trial that took place in 21 sites across Spain and Italy. The study included 33 women who had experienced a progressive disease after initially having a clinical benefit on a palbociclib plus endocrine therapy regimen. All patients were treated with the same dose of palbociclib that they received on their previous regimen, which was combined with the physician’s choice of endocrine therapy but had to be different from the previous treatment line. In addition to evaluating the clinical benefit of this strategy, the study also analyzed biomarkers to identify those patients who could benefit the most from this clinical approach.

The results of the scientific article were recently published in the journal Clinical Cancer Research, which showed that the study met its primary endpoint with 34% of patients experiencing a clinical benefit and 13% of tumors experiencing a loss in retinoblastoma (Rb) protein expression in tumor cells. Furthermore, a composite biomarker signature at baseline – low Rb score, high cyclin E1 score, ESR1 mutation – predicted worse outcome and represent a promising tool to identify patients who may not benefit from this strategy.

While the BioPER study confirms that a palbociclib rechallenge does not work for all patients, it did highlight the need to explore predictors of response to CDK4/6 inhibition. MEDSIR's PALMIRA trial, is.a larger randomized study that builds off the results of the BioPER study and could help to identify which patients would benefit from this treatment. This study (NCT03809988) is currently evaluating if palbociclib maintenance with an alternative endocrine therapy improves the antitumor activity of second-line treatment in 198 patients with HR+/HER2- advanced breast cancer.

"BioPER is the first prospective published trial to evaluate the antitumor activity, safety, and predictive biomarkers of palbociclib rechallenge in HR+/HER2- advanced breast cancer patients and its encouraging findings support further investigation in a larger randomized controlled trial."

- Dr. Antonio Llombart-Cussac

If you have an idea for a clinical trial or want to learn more about this or any of our other studies, contact us!


1. Cardoso et al. 3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3). Ann Oncol. 2017;28:16–33

2. O’Leary, et al. Cancer Discov. 2018; 8: 1390–1403

3. Albanell et al. Clin Cancer Res (2023) 29 (1): 67–80



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