Dasatinib activity prominent in subset of GIST patients

Dasatinib might have activity in some subsets of patients with imatinib-resistant gastrointestinal stromal tumors (GISTs), investigators have reported.

The tyrosine kinase inhibitor had a 29% rate of 6-month progression-free survival (PFS) in a nonrandomized, 50-patient study.

That PFS rate was well above the 10% threshold that would have constituted evidence of inactive treatment, but it “fell just short of our goal” of 30% that would have been considered evidence of drug activity, wrote Scott M. Schuetze, MD, PhD, of the department of internal medicine, University of Michigan, Ann Arbor, and his coauthors. The report was published in JAMA Oncology.

It was also higher than the 16% 6-month PFS rate reported in a randomized trial of sunitinib, which was approved for imatinib-resistant GIST treatment in 2006. However, it was lower than the 38% 6-month PFS rate reported for regorafenib, which was approved in 2013 for that indication, the researchers noted.

Exploratory analyses did identify a few biomarker-driven subsets that might particularly benefit from dasatinib therapy. Notably, the 6-month PFS rate was 50% for patients with tumors expressing phosphorylated SRC.

While intriguing, the results of the exploratory analyses are hampered by the small number of patients enrolled in the trial; only 14 patients in the study had phosphorylated SRC.

“Further studies should explore whether activated SRC is a prognostic biomarker of more indolent disease, or is a predictive biomarker of response to tyrosine kinase therapy,” the researchers wrote.

Patients in the study had imatinib refractory GIST. They received dasatinib 70 mg twice daily. They were enrolled in 2008-2009 and followed for at least 5 years.

In addition to previously receiving imatinib, most enrollees (80%) had already been treated with sunitinib as well. The study started before the approval of sunitinib in GIST, but after the approval of regorafenib, the investigators noted.

“Preclinical research suggested that dasatinib had higher potency against mutations in the activation domain of KIT and PDGFRA than imatinib and sunitinib,” the authors recounted.

This trial did provide some evidence in support of that preclinical data: One patient with a specific mutation in PDGFRA exhibited prolonged tumor control.

Bristol-Myers Squibb provided funding for the trial and dasatinib. Dr. Schuetze reported disclosures related to Novartis, Amgen, Janssen, Daiichi-Sankyo, Eli Lilly, and AB Science.

SOURCE: Schuetze SM et al. 2018 Apr 26. doi: 10.1001/jamaoncol.2018.0601.

Dasatinib might have activity in some subsets of patients with imatinib-resistant gastrointestinal stromal tumors (GISTs), investigators have reported.

The tyrosine kinase inhibitor had a 29% rate of 6-month progression-free survival (PFS) in a nonrandomized, 50-patient study.

That PFS rate was well above the 10% threshold that would have constituted evidence of inactive treatment, but it “fell just short of our goal” of 30% that would have been considered evidence of drug activity, wrote Scott M. Schuetze, MD, PhD, of the department of internal medicine, University of Michigan, Ann Arbor, and his coauthors. The report was published in JAMA Oncology.

It was also higher than the 16% 6-month PFS rate reported in a randomized trial of sunitinib, which was approved for imatinib-resistant GIST treatment in 2006. However, it was lower than the 38% 6-month PFS rate reported for regorafenib, which was approved in 2013 for that indication, the researchers noted.

Exploratory analyses did identify a few biomarker-driven subsets that might particularly benefit from dasatinib therapy. Notably, the 6-month PFS rate was 50% for patients with tumors expressing phosphorylated SRC.

While intriguing, the results of the exploratory analyses are hampered by the small number of patients enrolled in the trial; only 14 patients in the study had phosphorylated SRC.

“Further studies should explore whether activated SRC is a prognostic biomarker of more indolent disease, or is a predictive biomarker of response to tyrosine kinase therapy,” the researchers wrote.

Patients in the study had imatinib refractory GIST. They received dasatinib 70 mg twice daily. They were enrolled in 2008-2009 and followed for at least 5 years.

In addition to previously receiving imatinib, most enrollees (80%) had already been treated with sunitinib as well. The study started before the approval of sunitinib in GIST, but after the approval of regorafenib, the investigators noted.

“Preclinical research suggested that dasatinib had higher potency against mutations in the activation domain of KIT and PDGFRA than imatinib and sunitinib,” the authors recounted.

This trial did provide some evidence in support of that preclinical data: One patient with a specific mutation in PDGFRA exhibited prolonged tumor control.

Bristol-Myers Squibb provided funding for the trial and dasatinib. Dr. Schuetze reported disclosures related to Novartis, Amgen, Janssen, Daiichi-Sankyo, Eli Lilly, and AB Science.

SOURCE: Schuetze SM et al. 2018 Apr 26. doi: 10.1001/jamaoncol.2018.0601.

Dasatinib might have activity in some subsets of patients with imatinib-resistant gastrointestinal stromal tumors (GISTs), investigators have reported.

The tyrosine kinase inhibitor had a 29% rate of 6-month progression-free survival (PFS) in a nonrandomized, 50-patient study.

That PFS rate was well above the 10% threshold that would have constituted evidence of inactive treatment, but it “fell just short of our goal” of 30% that would have been considered evidence of drug activity, wrote Scott M. Schuetze, MD, PhD, of the department of internal medicine, University of Michigan, Ann Arbor, and his coauthors. The report was published in JAMA Oncology.

It was also higher than the 16% 6-month PFS rate reported in a randomized trial of sunitinib, which was approved for imatinib-resistant GIST treatment in 2006. However, it was lower than the 38% 6-month PFS rate reported for regorafenib, which was approved in 2013 for that indication, the researchers noted.

Exploratory analyses did identify a few biomarker-driven subsets that might particularly benefit from dasatinib therapy. Notably, the 6-month PFS rate was 50% for patients with tumors expressing phosphorylated SRC.

While intriguing, the results of the exploratory analyses are hampered by the small number of patients enrolled in the trial; only 14 patients in the study had phosphorylated SRC.

“Further studies should explore whether activated SRC is a prognostic biomarker of more indolent disease, or is a predictive biomarker of response to tyrosine kinase therapy,” the researchers wrote.

Patients in the study had imatinib refractory GIST. They received dasatinib 70 mg twice daily. They were enrolled in 2008-2009 and followed for at least 5 years.

In addition to previously receiving imatinib, most enrollees (80%) had already been treated with sunitinib as well. The study started before the approval of sunitinib in GIST, but after the approval of regorafenib, the investigators noted.

“Preclinical research suggested that dasatinib had higher potency against mutations in the activation domain of KIT and PDGFRA than imatinib and sunitinib,” the authors recounted.

This trial did provide some evidence in support of that preclinical data: One patient with a specific mutation in PDGFRA exhibited prolonged tumor control.

Bristol-Myers Squibb provided funding for the trial and dasatinib. Dr. Schuetze reported disclosures related to Novartis, Amgen, Janssen, Daiichi-Sankyo, Eli Lilly, and AB Science.

SOURCE: Schuetze SM et al. 2018 Apr 26. doi: 10.1001/jamaoncol.2018.0601.