Promoted by SOLTI and developed in scientific collaboration with the Vall d’Hebron Institute of Oncology (VHIO), the SOLTI-1910 RADIOLA study is the first prospective trial to provide evidence of the predictive value of the RAD51 functional test in metastatic gBRCA, HER2-negative breast cancer, allowing a more comprehensive reading than the genetic analysis based solely on BRCA1/2 gene mutations
The study shows that patients with germline alterations in the BRCA1 or BRCA2 genes whose tumors have low levels of RAD51 foci -lower functional DNA repair capacity- are more likely to respond to olaparib treatment (68.3% versus 21.4% of tumors with higher functional DNA repair capacity), confirming the biomarker’s value for identifying candidates with greater clinical benefit
Progression-free survival was also higher in patients with low RAD51 levels versus those with high levels, reinforcing the potential of the biomarker to select targeted therapies
These results, which position RAD51 as a potential biomarker to optimize the selection of gBRCA patients who may derive greater benefit from PARP inhibitors such as olaparib, are presented at the international San Antonio Breast Cancer Symposium (SABCS25)
SOLTI, a clinical cancer research group, presented today the results of the SOLTI-1910 RADIOLA study, which highlights the utility of a new biomarker developed by the Vall d’Hebron Institute of Oncology (VHIO), to identify patients with HER2-negative metastatic breast cancer who will benefit the most from treatment with a PARP inhibitor (olaparib). This functional test allows tumors to be classified according to their ability to repair DNA, verifying whether the cell’s natural system for DNA repair and survival, called homologous recombination, is functioning correctly or is damaged (in which case we refer to tumors with defective homologous recombination or HRD).
So far, this deficiency was mostly inferred through the presence of alterations in the BRCA1/2 genes, but this approach was not always sufficient to predict whether the patient would respond to PARP inhibitors.
To address this, the new RAD51 foci test was designed, capable of identifying HRD tumors, based on the detection of a protein involved in DNA repair, called RAD51, whose effectiveness is analyzed in this prospective study.
These results were made public during the last international breast cancer congress of the year, the San Antonio Breast Cancer Symposium (SABCS 2025), held in Texas (USA).
Thus, the RAD51 foci test has identified a subgroup of tumors, those with low RAD51 functional activity (and therefore defective homologous recombination), which shows up to 7 times greater likelihood of responding to olaparib treatment compared to those that maintain competent homologous repair.
According to Dr. Isabel Pimentel, first author of the study, medical oncologist at Vall d’Hebron University Hospital and researcher at the VHIO Breast Cancer Group: “RAD51 identified among patients with a pathogenic variant in the BRCA1 or BRCA2 genes, a subgroup with defective homologous recombination whose response rate to olaparib was 68.3%, compared to 21.4% in tumors without this functional deficiency.”
“We know that patients with pathogenic variants in the BRCA1 or BRCA2 genes usually benefit from PARP inhibitors, but not all respond. With the RADIOLA clinical study, we wanted to understand which tumors actually present a defect in DNA repair function that makes them especially sensitive to treatment,” says Dr. Judith Balmaña, principal investigator of the study, medical oncologist at Vall d’Hebron University Hospital, and head of the VHIO Hereditary Cancer Genetics Group, adding that RADIOLA addresses a specific clinical need: “It allows for more tailored decisions for the patient and avoids unnecessary or low-benefit treatments.”
A detailed analysis of the study results shows in Cohort 1 (comprising patients with a mutation in the BRCA1/2, PALB2, or RAD51C/D genes), an objective response rate of 68.3% in tumors with RAD51-low foci, compared to 21.4% in tumors with RAD51-high foci. This difference was also reflected in a longer progression-free survival (7.1 months vs. 5.6). In Cohort 2 (comprising patients classified as RAD51-low without a pathogenic variant in a DNA repair gene), more modest signs of benefit were observed.
Dr. Aleix Prat, co-principal investigator of the study and director of the Clínic Barcelona Comprehensive Cancer Centre, notes: “If these results are confirmed in larger studies, RAD51 could become a complementary filter to the detection of mutations in the BRCA genes to decide which patients should receive a PARP inhibitor and where the expected benefit is lower.”
The findings from RADIOLA consolidate an idea that is gaining increasing weight in oncology: it is not enough to know the pathogenic variants of the tumor; it is necessary to understand how its actual DNA repair machinery works. Combining genetic information with functional biomarkers like RAD51 allows for a more accurate picture of tumor biology, and with that, select with greater precision the patients who could benefit from a PARP inhibitor.
“RAD51 allows us to go beyond the genetic profile and understand the functional behavior of the tumor in clinical practice. These types of tools provide a layer of precision that is key to moving toward truly personalized therapies and avoiding treatments that may not deliver the expected benefit,” says Dr. Prat.
Looking ahead, this approach could have a particularly relevant impact in early-stage disease, an area where there is active work to optimize treatments and reduce the toxicity associated with some interventions. In this line, Dr. Balmaña concludes: “In patients who will receive neoadjuvant treatment (before breast tumor surgery) or adjuvant treatment (after surgery), a functional biomarker like RAD51 could help us identify which patients would benefit from a PARP inhibitor without the need for chemotherapy. It is a promising route toward more secure, biologically-driven therapeutic optimization.”
RADIOLA is a Phase II, open-label, multicenter study that included 65 patients with HER2-negative metastatic breast cancer. The RADIOLA study has been carried out in collaboration with the Vall d’Hebron Institute of Oncology (VHIO) and supported by AstraZeneca.
About the RADIOLA study (SOLTI-1903)
RADIOLA is an open-label, multicenter Phase II trial promoted by SOLTI, evaluating the predictive value of the RAD51 functional test in HER2-negative metastatic breast cancer patients treated with olaparib. The trial examines RAD51’s ability to identify functional deficiencies in homologous recombination and its association with objective response, progression-free survival, and clinical benefit.
