A team of researchers from the Bellvitge Biomedical Research Institute (IDIBELL), the Catalan Institute of Oncology and the Bellvitge Hospital are carrying out the first clinical trial aimed at lung cancer patients with untreated brain metastases. The trial, published today in the Journal of Clinical Oncology, shows that the combination of chemotherapy and immunotherapy applied from the moment of diagnosis is effective both in the lung and in the brain. This makes it possible to attack both fronts from the start, keeping brain tumors stable for 7 months, at which time cranial radiotherapy will become necessary.
Lung cancer is the solid tumor that most commonly metastasizes to the brain. In fact, almost a quarter of diagnosed patients present them at the time of diagnosis. In this regard, traditionally, before receiving whole-body treatment, brain metastases are treated with cranial radiation therapy. This can delay the application of systemic treatment and unfortunately has a negative impact on neurological function, especially when the spread of the tumor requires radiation therapy to the whole brain.
“The combination of chemo-immunotherapy that we used in this study has proven to be effective both in the brain and in the rest of the body and allows us to postpone the use of brain radiotherapy. In addition, we can continue to administer chemo-immunotherapy even when radiotherapy becomes necessary, allowing us to act on the disease throughout the body at all times”, points out Dr. Ernest Nadal, head of the Thoracic Tumors research group at IDIBELL and the Catalan Institute of Oncology, and leader of the project.
Combination of chemotherapy and immunotherapy without neurocognitive involvement
In this phase 2 trial, promoted by the Spanish Lung Cancer Group, 40 patients received Carboplatin and Pemetrexed as chemotherapy, combined with Atezolizumab, an antibody that stimulates the ability of the immune system to attack to cancer cells.
The results of the study show that with chemo-immunotherapy almost all patients who respond at the systemic level also do so at the brain level. In fact, more than 40% of patients partially or totally reduced the disease. In addition, it kept brain metastases stable for about 7 months, more than double that with conventional treatment.
“Until now, patients with brain metastases were excluded from clinical trials if they had not previously been treated with brain radiation therapy. We wanted to design a specific therapeutic approach for them. That is why we have paid great attention to the effects on the brain of applying systemic treatment from the beginning and postponing radiotherapy”, explains Dr. Jordi Bruna, author of the article, head of the Neuro-Oncology research group at IDIBELL and Coordinator of the Neuro-Oncology Functional Unit of the Catalan Institute of Oncology and the Bellvitge University Hospital.
To standardize the results, international criteria were used to monitor the evolution of brain metastases during treatment. In addition, the patients underwent neuropsychological evaluations to know their cognitive state at all times.
Valentín Navarro, co-author of the article and coordinator of the Clinical Research Unit of the Catalan Institute of Oncology, explains that they have used an innovative statistical method that allows the efficacy and safety of the treatment to be analyzed in real time. “In this way we have been able to ensure that no patient has crossed the safety threshold that we had established at the beginning”, he comments.
The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).