Barcelona, May 29, 2020.- The VHIO is presenting a series of new breast cancer treatments at one of the year’s major cancer research congresses. The annual congress of the American Society of Clinical Oncology (ASCO) is normally held between the end of May and beginning of June in Chicago as a forum to discuss the latest advances in research on a disease that is one of the principal causes of death around the world.
This year, like so many other congresses, particularly in the health field, it has been forced to go online because of the pandemic situation caused by COVID-19.
Some of the studies presented this year making progress in developing breast cancer treatments include researchers from the Vall d’Hebron Institute of Oncology (VHIO). Ever-improving knowledge of the molecular profile of this tumor is making it possible to develop strategies aimed at the weak points of the disease, leading to promising results.
New treatment for HER2-positive patients with cerebral metastasis
Dr. Mafalda Oliveira is one of the researchers who have taken part in the HER2CLIMB study, which tested the effectiveness of a combination of tucatinib with trastuzumab and capecitabine in metastatic patients with HER2-positive breast cancer, including those with cerebral metastasis. “Now at ASCO we have presented the specific results in the subpopulation of patients with cerebral metastasis, where the results of this treatment are particularly significant, indicating that it could become a new standard of care.”
The data presented at this congress shows how, in previously treated patients with cerebral metastasis, this triple combination is capable of doubling the intracraneal objective response rate, reducing the risk of intracraneal progression by two thirds and cutting the risk of death by almost half. “These are good results for patients with cerebral metastasis, whether they have active metastasis or have previously been treated. This is undoubtedly the main point we can highlight in this study,” added Dr. Oliveira.
It must be borne in mind that there are currently limited treatment options for metastatic HER2-positive breast cancer patients whose disease progresses after using standard directed treatments like trastuzumab, pertuzumab and T-DM1. Patients with cerebral metastasis are particularly difficult to treat. “That is why it is so important to be able to develop new treatments for these patients, and this triple combination points to a promising new direction,” continued Dr. Oliveira.
Olaparib, effective as monotherapy
Therapies aimed at a molecular target on the cancer are increasingly proving more effective in treating the disease. Sometimes this is in combination with other drugs, but not always, as increasing numbers of treatments of this kind are achieving positive results as monotherapies. This is the case with olaparib, for example, an inhibitor of the enzyme poly (ADP-ribose) polymerase (PARP). The intermediate analysis of the phase IIIB study LUCY in patients with HER2-negative metastatic breast cancer and germline mutation in BRCA1 or BRCA2 confirms its real, safe clinical effectiveness as a sole treatment.
“The data we’re presenting now is consistent with previous studies and supports the use of olaparib as an alternative treatment to chemotherapy for this type of patient, with the benefits this involves for improving their quality of life,” said Dr. Judith Balmaña, one of the researchers who has taken part in the study.
By inhibiting the PARP enzyme, which helps repair DNA, olaparib prevents tumor cells repairing themselves, and they are destroyed. The BRCA genes form part of a mechanism for repairing damage to DNA called “homologous recombination”. “There was a suggestion that the strategy of using this PARP inhibitor would give results in patients whose tumors have a mutation in the genes involved in repairing DNA, and it has,” added Dr. Balmaña.
More than 250 patients have taken part in the LUCY study which was intended to provide additional data on the effectiveness and safety of monotherapy with olaparib in the real world to validate previous observations in the OlympiaAD trial. The treatment showed better results than the standard of care for patients with HER2-negative metastatic cancer with BRCA germline mutations.
A better hormone combination strategy for luminal patients with cyclin inhibitors
The current standard treatment for patients with luminal metastatic breast cancer is the combination of an aromatase inhibitor – an oral endocrine agent that drastically reduces estrogen levels – and an inhibitor of the cyclin-dependent kynases (CDKs) 4 and 6, which acts by slowing down the cellular cycle.
“Although aromatase inhibitors like letrozole have made up the first line of hormone treatment for advanced breast cancer for the last couple of decades, recent data suggested that fulvestrant – an intramuscular antagonist of pure estrogen receptors – works better than anastrozole, another aromatase inhibitor used in patients who have not previously had hormone therapy,” said Dr. Meritxell Bellet. “We also knew that the combination of fulvestrant and palbociclib, a CDK4/6 inhibitor, was better than fulvestrant-placebo in the most advanced lines of treatment,” she continued. Meanwhile, fulvestrant and ribociclib, another CDK4/6 inhibitor, had been associated with very long progress-free survival and even improved overall survival compared to fulvestrant plus placebo. “Considering all this, we believe we need to identify the best endocrine agent to combine with a CDK4/6 inhibitor, specifically palbociclib in the first line of treatment,” said Dr. Bellet.
To provide answers, the PARSIFAL study was set up, also including the VHIO associate translational researcher Dr. Javier Cortés. It recruited 486 patients who were divided equally into two branches of research. Half received the standard treatment of palbociclib and letrozole and the other half were given palbociclib combined with fulvestrant. Despite the initial assumption that fulvestrant-palbociclib would be best, the results of this trial do not demonstrate that progression-free survival is longer in the combination with fulvestrant, although neither do they show that it is shorter.
This data means the combination with letrozole continues to be the leading treatment because it also has the advantage of being administered orally. The strategy of many studies testing fulvestrant with new treatments aimed at moving to aromatase inhibitors together with CDK4/6 inhibitors is also corroborated. “We know that the sequence of aromatase inhibitors with CDK4/6 inhibitors is related to the acquisition of mutations in the estrogen receptor gene that cause the progression of the disease. And in this situation we know that fulvestrant can still be effective against tumors,” concluded Dr. Bellet.
Dr. Oliveira, Dr. Bellet and Dr. Cortés belong to the VHIO’s Breast Cancer Group led by Dr. Cristina Saura.
Dr. Balmaña is the principal investigator of the VHIO’s Hereditary Cancer Genetics Group.