Immunotherapy: specialists present their results at ASCO 2016
What has truly changed everything in immunotherapy against cancer is the discovery of immunomodulators. These molecules will “release” the immune system and enable it to attack cancer cells. The immune system does in fact respond to cancers, but the response is not sufficient. It has to be stimulated to ensure that it is strong enough to battle its opponent. Among the molecules able to unleash the action of the immune system and already to be proven effective are anti-CTLA-4 antibodies and molecules targeting PD-1 or PD-L1. The anti-PD-1/PD-L1 molecules prove effective against skin melanomas and bronchial cancers, as well as ENT, bladder, kidney and ovarian cancers. The list of cancers that could benefit from these new therapies is constantly growing.
>> Uveal melanoma
Institut Curie is a national reference in uveal melanoma treatment. As long as this rare cancer is localised, standard treatments are effective in local control of the disease. As soon as it begins to spread however, there is no effective treatment against it. Dr Sophie Piperno-Neumann, clinical oncologist at Institut Curie, assessed the effectiveness of anti-PD-1 in 21 patients suffering from metastatic uveal melanoma. This first study shows no evidence-based activity of this immunotherapy. However it is possible that anti-PD1 may be effective in certain patients. The new clinical trials must endeavour to reveal specific biomarkers of “responsive” patients.
>> Cortical adenoma
Professor Christophe Le Tourneau, who ran the early trials at Institut Curie, revealed the results of the phase I JAVELIN trial with anti-PD-L1 avelumab in 37 patients suffering from metastatic malignant cortical adenoma that have progressed following a first round of chemotherapy. This rare cancer occurs in the adrenal glands, above the kidneys. This was the first data for an immunotherapy for this tumour location. The first results showed effectiveness in certain patients with good tolerance.
>> Anticipate the response thanks to circulating tumour DNA
Today 20 to 40% of patients treated by these immunotherapies show a significant decrease in the size of their cancer lesions and 10 to 15% of patients enjoy lasting responses. In addition to research to improve their effectiveness, one of the challenges is to identify biomarkers to quickly find out whether these treatments are effective in patients.
Circulating tumour DNA (ctDNA) is a new quantitative blood biomarker, which can be taken via a simple blood test to track mutations of tumour being treated. Would it be possible to evaluate the response to immunotherapies thanks to ctDNA? This is one of the goals of the ALCINA study coordinated by Dr François-Clément Bidard, clinical oncologist. Patients treated by anti-PD-1 immunotherapy (nivolumab, pembrolizumab), for lung cancers, uveal melanomas and colorectal cancer at Institut Curie were therefore monitored to find out whether the early ctDNA quantitative variations are predictive of the effectiveness of these treatments, for which radiological evaluation is difficult. The results suggest that ctDNA is a promising biomarker for monitoring these new treatments.