Predicting the effectiveness of immunotherapy
The ability to know quickly whether or not a treatment is effective is a key challenge. And all the more so with the latest generation of anti-PD-L1 and PD-L1 antibody immunotherapy. Although we see very effective results in 10% to 20% of patients with these types of immunotherapies, for all cancer types taken together, for several months or years, certain patients do not respond and sometimes their tumor even progresses.
“Imaging dos not always give a response to the treatment early enough and precisely enough”, explains Dr. François Clément Bidard, medical oncologist at Institut Curie. “So we started to look at the potential of circulating tumor DNA (ctDNA)”.
When it develops, a tumor “discharges” some of its cells and genetic material - DNA - into the blood. We talk about circulating tumor cells and ctDNA. Thanks in particular to the work of Prof. Jean-Yves Pierga and Prof. François-Clément Bidard, we know that if we find one or the other this appears to be an indicator of the following:
- risks of relapse and occurrence of metastases
CtDNA, an indicator of response to immunotherapy
“We wanted to know whether the change in the level of ctDNA in the blood of patients treated using anti-PD-L1 and PD-L1 antibodies could predict the effectiveness of the treatment”, explains the physician-researcher. In patients with non-small cell lung cancer, uveal melanoma or another type of colon cancer, the rate of ctDNA seems to be a good indicator of the response to treatments and to be closely linked to the size of the tumor. Furthermore, if the ctDNA can no longer be detected in a patient, the patient has a lasting response to the treatment.
This is the first study to highlight the potential of ctDNA to predict the response to the brand new immunotherapy treatments. “This proof of concept is extremely important since one of the challenges of immunotherapy is now to find biomarkers to identify which patients respond and which don’t, thus avoiding unnecessary treatments”, adds François-Clément Bidard.
In parallel, research in immunotherapy needs to continue in order to:
- Discover other new biomarkers that predict a response to treatment.
- Understand the mechanisms of immunotherapy and why some patients respond while others don’t.
This is one of the challenges of the Cancer Immunotherapy Center at Institut Curie.
Beyond immunotherapy, it is also additional proof of the importance of circulating biomarkers, whether circulating tumor cells or ctDNA, in oncology. Finding out more about a type of cancer, its evolution or the response to treatment, based on a simple blood sample, is a hope that is increasingly becoming reality.
Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study.
Cabel L, Riva F, Servois V, Livartowski A, Daniel C, Rampanou A, Lantz O, Romano E, Milder M, Buecher B, Piperno-Neumann S, Bernard V, Baulande S, Bieche I, Pierga JY, Proudhon C, Bidard FC.
Ann Oncol. 2017 Apr 29. doi: 10.1093/annonc/mdx212. [Epub ahead of print]