Chicago, 3 june 2019
ASCO 2019

Paediatric cancers:
Larotrectinib, first targeted therapy for childhood solid tumours, shown to be effective

Three studies on Larotrectinib, conducted in partnership with Gustave Roussy and presented at ASCO, show the value of this selective TRK inhibitor both in childhood and adult oncology. Larotrectinib is the first agent capable of selectively blocking TRK fusions, genetic abnormalities implicated in a number of cancers, most particularly rare cancers in adults and children. These arise early in the development of the cancer and remain present up to its possible dissemination. Their action involves sending signals that stimulate growth of cancer cells.

Concomitantly, the results of the MAPPYACTS international trial, also presented at ASCO and led by Gustave Roussy in France, Ireland and Italy, show that sequencing of tumours in children in relapse or with treatment failure can lead to the identification of young patients likely to benefit from Larotrectinib treatment.

MAPPYACTS shows that precision medicine is possible in children with treatment failure

The MAPPYACTS (MoleculAr Profiling for Pediatric and Young Adult Cancer Treatment Stratification) programme is a multicentre clinical study aiming to perform tumour molecular analysis in refractory cases or relapse in children, in order to identify specific abnormalities which might represent treatment targets. This programme is mainly supported by the ARC Foundation for Cancer Research, Imagine for Margo and the French National Cancer Institute.

This was conducted on 500 French, Italian and Irish children with cancer. Half of them were aged below 13. It was possible to analyse the data from 390 of these patients. 271 of them (70%) had at least one abnormal gene which was a potential treatment target. 72 of these did receive such treatment, most of them in the AcSé-ESMART clinical trial.   
Some of the genetic damage identified involved TRK fusions. “The European MAPPYACTS programme, led by Gustave Roussy at the national level, analysed the tumour in children with treatment failure in order to move to targeted therapy. In France this genome sequencing identified 6 young patients with TRK fusion,” explained Professor Gilles Vassal, Director of Clinical Research at Gustave Roussy and Chair of ITCC (Innovative Therapies for Children with Cancer).

It was possible to enrol these 6 patients in therapeutic trials testing Larotrectinib, a novel targeted agent.

Poster discussion
Saturday 1st June from 8:00 AM to 11:00 AM (Chicago time),
Hall A, followed by discussion from 1:15 PM to 2:45 PM, Room S504
Can paediatric and adolescent patients with recurrent tumors benefit from a precision medicine program? The European MAPPYACTS experience
Read the abstract No. 10018

The response rate with Larotrectinib reaches 94% in paediatric cancers

Larotrectinib has already been authorised in the United States, where it is indicated for adult and paediatric tumours with TRK fusions, regardless of tumour type. As such, it is the first targeted therapy to be authorised for an “agnostic” indication. The European Medicines Agency is currently examining an application. In France, while awaiting marketing authorisation, this agent has been available for some weeks and can be used under a cohort authorisation for temporary use arrangement. It should, therefore, soon become the first targeted therapy authorised for treatment of solid tumours in children.
A first study on Larotrectinib showed its long-lasting efficacy and safety in children with cancer carrying TRK fusions. 38 participants were recruited from two Larotrectinib clinical trials in which they had been entered after tumour genome sequencing revealed TRK abnormalities.

Of the 34 patients whose data could be evaluated, the overall response rate to Larotrectinib reached 94%. In 84% of the cases the median duration of the response exceeded 1 year.

Oral presentation
Sunday 2 June from 8:12 AM to 8:24 AM (Chicago time), Room S504
Larotrectinib efficacy and safety in pediatric TRK fusion cancer patients
Read the Abstract No. 10010

Larotrectinib efficacy on cerebral metastases and primary central nervous system tumours

The second study, conducted in collaboration with Gustave Roussy, showed that Larotrectinib was effective in patients with brain cancers carrying TRK fusions; the agent also offered lasting disease control in the presence of metastatic disease.

The study involved 14 patients, aged from 2 to 79, with cerebral tumours treated with Larotrectinib over several months. Five of these had secondary central nervous system cancer in the form of cerebral metastases, the other 9 primary central nervous system tumours with TRK fusions.

Larotrectinib was shown to be effective on cerebral metastases in patients with cancer bearing TRK fusions. Confirmed responses and durable disease control were seen with metastatic disease and with primary central nervous system tumours. These findings suggest that TRK fusions should be sought in all cancers, including primary central nervous system tumours.

Oral presentation
Monday 3 June from 3:15 PM to 3:27 PM (Chicago time), Room S102
Activity of larotrectinib in TRK fusion cancer patients with brain metastases or primary central nervous system tumors
Read the abstract No. 2006

Improvement in quality of life in children on Larotrectinib

In the last trial (July 2017), conducted in collaboration with the Gustave Roussy Department of Childhood and Adolescent Oncology, researchers evaluated the effects of Larotrectinib on patient quality of life. A number of quality of life questionnaires were completed at various points in their treatment by 37 patients (13 children and 24 adolescents and adults) with different tumours having TRK fusions in common. Participant responses showed rapid improvement in every aspect: physical, emotional, social, cognitive and scholastic. Although these results are derived from small samples, they reflect a marked improvement in quality of life in children, adolescents and adults treated with Larotrectinib for cancer with TRK fusions.

Saturday 1st June from 1:15 PM to 4:15 PM (Chicago time), Hall A
Patient-reported outcomes from two global multicenter clinical trials of children and adults with tropomyosin receptor kinase (TRK) fusion cancer receiving larotrectinib
Read the abstract No. 6602


Listen to Pr. Gilles Vassal’s explanations





Catégorie de la page: