Childhood solid tumours: first results of paediatric Metro-PD1-study
Childhood solid tumours: first results of paediatric Metro-PD1-study
BRUSSELS – The Anticancer Fund proudly presents the initial findings of the French-Belgian Metro-PD1 study testing a treatment with nivolumab in combination with metronomic chemotherapy in children and adolescents with relapsing/refractory solid tumours. The study reveals new possible treatment avenues for paediatric solid tumours. The results were published in the European Journal of Cancer.
Solid tumours represent about 30% of all paediatric cancers. Some examples of solid tumours that occur in children but rarely develop in adults are neuroblastoma, osteosarcoma and retinoblastoma. Though most of these children will become cancer-free thanks to treatment, 30% eventually suffer from recurrent or refractory disease.
Controlling recurrent and refractory tumours is challenging because of the limited efficacy of traditional treatments at that stage. 20% of paediatric cancer patients still die from recurrent or refractory disease. Finding new treatment options that work better and have little side effects is therefore crucial for these children and their families.
Enhancing immune therapy in children
Recently, immune therapy, such as nivolumab, has yielded considerable results for many, mainly adult, cancer patients. Unfortunately, immune therapy hasn’t lived up to its expectations in children affected by solid tumours.
It is hypothesised that adding other treatments to immune therapy may improve its efficacy, by targeting a variety of cellular mechanisms used by the tumour to escape the immune therapy. To find the right drugs to overcome the problem of resistance to immune therapy in paediatric tumours is therefore a crucial step, made (more) difficult by the almost infinite number of possibilities to be tested.
Adding small doses of chemotherapy
Based on extensive preliminary research, the investigators of the Metro-PD1 trial identified a number of chemotherapeutic drugs that could possibly enhance the effect of immune therapy. In the Metro-PD1 trial, they tested if adding low, daily doses of selected chemotherapy (so called metronomic chemotherapy) in children and adolescents with relapsing/refractory solid tumours could get nivolumab to work better.
“It’s been very tough for children, their parents and their oncologists to experience that immune therapy doesn’t work well for paediatric solid tumours. Metro-PD1 is a great effort both to offer a therapeutic option to French and Belgian children in need and to attempt to change this.” says Gauthier Bouche, director of clinical research at the Anticancer Fund.
In a first stage, with 16 participants, it was determined which set of chemotherapy should be used with nivolumab. The results were recently published in the European Journal of Cancer. It was found that, from the 3 options tested (nivolumab combined with 1 drug, 2 drugs or 3 drugs), the one with 3 chemotherapeutic drugs, namely capecitabine, cyclophosphamide and vinblastine, was safe and deemed the most likely option to help the immune therapy work.
The second stage of the trial has started
The aim of the second stage of the trial, with a larger number of patients, is to find out if this combination identified in the first stage does indeed work better than the chemotherapy alone. This stage of the trial is currently ongoing.
Prof. Nicolas André, paediatric oncologist at La Timone University Hospital, Marseille, France, explains: “It was very exciting to design a trial built upon the different immune properties of metronomic chemotherapy and combine them with nivolumab. It moves the field of metronomics into the exciting area of immunotherapy for children with refractory malignancies. With the good safety profile and the signals of efficacy we’ve seen in the first part of the trial, I can't wait to have the results of the phase 2 part to learn more about the value of the combination.”
The Anticancer Fund provides direct funding to this trial and channels funding from KiCa Fund, managed by the King Baudouin Foundation, KickCancer, and Alexine Clarysse Fund.