..Drafting.
Targeted therapies, focused on a specific molecular characteristic of the tumor, which is key to its continuous invasion or division, are increasingly playing a leading role in cancer treatment. So far the use of olaparib, a drug that inhibits the PARP protein, essential in DNA repair processes, in breast cancer was restricted to the context of metastatic disease in patients with a genetic alteration in BRCA1 o BRCA2. Now, the results of the Olympia study, recently published in The New England Journal of Medicine and that are presented in the plenary session of the virtual congress of DISGUST, support the expansion of the use of olaparib in patients diagnosed with early breast cancer.
The results of the Olympia study support the expansion of the use of olaparib in patients diagnosed with early breast cancer
“These data represent a great clinical breakthrough, because they indicate that patients with an inherited genetic alteration in BRCA1 or BRCA2 may receive a targeted treatment with a high impact on your chance of being cured, since we are talking about the initial stages of the disease”, explains the Drag. Judith Balmaña, responsible for the Cancer Genetics Group and member of the Breast Cancer Unit of the Vall d’Hebron Institute of Oncology (VHIO), who is co-author of the publication, one of the researchers of the study Olympia, forming part of its steering committee on behalf of the Solti group and who has also been the co-chair of the study’s genetics subcommittee on behalf of VHIO.
Reduced risk of relapse
In this studio Olympia A total of 1,836 patients with a germline mutation participated in BRCA1 O BRCA2 with early and HER2 negative breast cancer. The study evaluated the efficacy of olaparib after conventional chemotherapy treatment (neoadjuvant or adjuvant), surgery, and radiation therapy to prevent disease relapse. “It should not be forgotten that these genetic alterations in BRCA1 or BRCA2 usually predispose to diagnosis of potentially aggressive tumors and at a young age ”, Dr. Balmaña emphasizes.
Dr. Judith Balmaña: “We have shown that olaparib achieves a reduction of more than 40% in having a relapse of the disease compared to the control group”
The study randomized the patients into two groups, one receiving olaparib and the other receiving placebo. In both cases together with hormonal treatment if the tumor was hormone receptor positive. All this after completing the surgical treatment, chemotherapy and conventional radiotherapy. The treatment was administered for a year and it was found that olaparib was indeed capable of significantly reducing the risk of relapse. “We have shown that olaparib achieves a greater than 40% reduction in having a relapse of the disease compared to the control group “, explains Dr. Judith Balmaña.
Analyzing the data obtained at three and a half years of follow-up, it could be seen that the absolute reduction in the risk of distant relapse in the olaparib group was 7% compared to the control group. “Regarding invasive disease relapse, this means that at three years in the placebo group 77% of the patients did not have a relapse, and this benefit was extended to 86% in the patients treated with olaparib. This represents an important healing opportunity and, without a doubt, it will mean a change in clinical practice ”, adds the doctor. Likewise, it emphasizes that the toxicity of this drug is low and that its administration is oral, which allows maintaining a good quality of life.
The toxicity of this drug is low and its administration is oral, which allows maintaining a good quality of life
Mutations in BRCA1 o BRCA2
The genes BRCA1 Y BRCA2 produce tumor suppressor proteins. Thus, they help repair damaged DNA and therefore ensure the stability of the genetic material of each of the cells. However, when a mutation occurs in one of these genes, the corresponding protein stops working properly. Therefore, there is a greater chance of having additional genetic alterations that can lead to cancer. A woman’s risk of developing breast or ovarian cancer is greatly increased if she inherits a harmful gene mutation BRCA1 or in the gene BRCA2. Some studies indicate that women who inherit any of these mutations have up to a 70% chance of developing breast cancer. In contrast, this probability is 12% in the non-carrier population.
A mutation in the genes BRCA1 O BRCA2 it is an increased risk of developing cancer. Furthermore, it also makes tumors especially sensitive to treatment with olaparib. It is an inhibitor of the PARP protein and is the first treatment aimed at tumor cells that have a deficiency in the homologous recombination DNA repair pathway. Such are precisely those tumors with a mutation in BRCA1 o en BRCA2.
“This drug had already shown its usefulness in the treatment of patients with metastatic breast cancer. With the results of the Olympia study, it takes a step forward and is shown to offer an important benefit in the possibility of cure in an initial stage of the disease “, concludes the Dr. Saura, Head of the Breast Cancer Unit of the Vall d’Hebron University Hospital (HUVH). She is also head of the Breast Cancer Group at the Vall d’Hebron Institute of Oncology (VHIO).
Olympia Study Results Show Olaparib Offers Significant Curable Benefit in Early Stage Breast Cancer
This study has been possible thanks to an alliance to carry out a clinical study between academia and the pharmaceutical industry worldwide. In Spain, the cooperative group Solti and the cooperative group Geicam for breast cancer research have participated as academic groups that belong to BIG (Breast International Group). “Together they have recruited almost 122 patients, which represents almost 10% of the total“, As detailed by the VHIO in a statement.
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