Vall d’Hebron takes part in the development of the first effective drug for a subtype of GIST orphan of treatment

César Serrano
  • Avapritinib is the first effective drug in patients with advanced gastrointestinal stromal tumors (GISTs) carrying the PDGFRA D842V mutation. This novel drug was specifically designed to target this mutation.
  • Avapritinib induced tumor reduction in 55 of the 56 patients whose GIST harbored the PDGFRA D842V mutation, with almost 90% of success in obtaining a partial or complete response.
  • Other inhibitors, which were a therapeutic breakthrough, have shown low activity in patients with GIST carrying this mutation, for whom there was no treatment available.

Barcelona, June 30, 2020.– An international multicenter study, in which the Vall d’Hebron Institute of Oncology (VHIO) was involved, has demonstrated the safety and efficacy of avapritinib, a new targeted tyrosine kinase inhibitor therapy, in the treatment of advanced gastrointestinal stromal tumors (GIST) harboring the PDGFRA D842V mutation. The significance of this work lies in that no effective therapies were available for these patients, who had a survival of barely a year. This novel therapy was proven to be effective in almost the totality of patients.

The Lancet Oncology published the results of this study, which principal investigator is Dr. Michael Heinrich, at the OHSU Knight Cancer Institute of Portland, USA. The only Spanish researcher involved in the study is Dr. César Serrano, a medical oncologist at Vall d’Hebron University Hospital and leader of the Sarcoma Translational Research Group at the Vall d’Hebron Institute of Oncology (VHIO). Dr. Serrano was a member of the international team that conducted this clinical trial.

Dr. César Serrano, principal investigator at VHIO’s Sarcoma Translational Research Group.

“This is a step forward in the development of precision medicine in cancer. Once again, we turned a specific mutation into a therapeutic target, which allowed us to develop an effective treatment”, says Dr. César Serrano.

Although this is a phase 1 trial performed to assess the safety of the drug, the promising results obtained allow us to be optimistic about this new therapy. “This new drug was recently approved by the Food and Drug Administration (FDA) and is currently under evaluation by the European Medicines Agency (EMA). Approval of this therapy from health authorities represents a milestone in oncology, as it will be the first treatment for patients with GIST carrying this mutation”, explains Dr. Serrano.

Orphan-drug patients
GIST, a type of sarcoma, is a rare type of tumor, which hinders the development of clinical trials to find active drugs. This has a negative impact on patients. Up to 85% of GISTs harbor an oncogenic mutation in a tyrosine kinase receptor, either the KIT or PDGFRA gene; therefore, they are the ideal target for new treatments. The development of imatinib in the early 21st century represented a breakthrough in the treatment of the disease, as metastatic or unresectable GIST went from being a fatal disease to being a manageable, survivable disease, with a lasting response and a better overall survival.

“However, patients carrying the PDGFRA D842V did not benefit at all from imatinib or other tyrosine kinase inhibitors that were approved later. Avapritinib has been designed to attack in a powerful and selective way this specific resistance mutation. In the light of the results obtained in this trial, it is evident that it works” says Dr. César Serrano. “Now there is a really effective drug for patients for whom there was no treatment available”.

GIST is a rare tumor, as it only accounts for 1-3% of malignant gastrointestinal tumors. Even fewer patients have this mutation, accounting for only 5% of all GISTs. “Although they are few, these patients needed that a medicine was developed, as there wasn’t an alternative for them and their prognosis was unfavorable, with an overall survival of about five months, similar to that of all GIST patients in the pre-imatinib era”, adds Dr. Serrano.

Long-lasting response in pretreated patients
A total of 56 patients with GIST harboring the PDGFRA D842V mutation took part in the study, of whom 55 exhibited tumor reduction, with near 90% of success in obtaining a partial or complete response. These results are encouraging, if we consider that 96% of participants had metastatic disease and up to 61% had clinically-advanced disease. To date, other drugs such as imatinib, sunitinib and regorafenib –all being type 2 inhibitors– had demonstrated low or no activity in these patients.

“Although most patients had received other tyrosine kinase inhibitor therapies, response to avapritinib is also long-lasting. The results confirm the potential of the new drug to provide an enduring clinical benefit in these patients with GIST”, explained Dr. César Serrano, who added that most of adverse events related to avapritinib did not result in treatment withdrawal, could be managed, and were proportional to the dose.



Heinrich MC, Jones RL, von Mehren M, et al. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol. 2020;21(7):935-946. doi:10.1016/S1470-2045(20)30269-2