CHICAGO -- A novel targeted agent failed to find much clinical benefit in HER2-negative metastatic breast cancer, although it may still find a role for a subgroup of patients, researchers found.
The fibroblast growth factor receptor 1 (FGFR1) inhibitor dovitinib held clinical benefit for no more than 12% of patients without high expression of the target, Fabrice Andre, MD, PhD, of the Institut Gustave-Roussy in Villejuif, France, and colleagues found
The drug achieved stable disease or at least 50% tumor shrinkage at 24 weeks for 15% of patients with high levels of both FGFR1 and hormone receptors, the group reported here at the American Society of Clinical Oncology meeting.
Although these results weren't good enough for the phase II trial to move forward, Andre suggested it may be too early to give up on the drug entirely.
Antitumor activity couldn't be ruled out in the hormone receptor-positive, FGFR1-amplified group, he told attendees.
He pointed to a 25% rate of partial response that couldn't be confirmed or stable disease at 24 weeks in this small group.
Only 8% to 10% of breast cancers show amplification of FGFR1.
But those that do are often the poor prognosis, HER2-negative luminal B type of breast cancers that are associated with endocrine therapy resistance despite estrogen receptor expression, he noted.
Dovitinib inhibits FGFR1 along with other receptor tyrosine kinases and has been tested in melanoma and renal cell tumors.
Andre's group tested it in an open-label phase II trial among 68 patients with metastatic HER2-negative breast cancer.
Patients received 500 mg of oral dovitinib once a day in a five-day-on, two-day-off schedule.
Partial response by RECIST criteria at four to six weeks that could not be confirmed beyond that point was achieved by 15% of patients with FGFR1- and hormone receptor-positive disease (three of 21) but no patients in the other tumor subgroups.
Stable disease as the best response was seen in:
Median progression-free survival was 3.6, 3.5, and 2.1 months, respectively.
The adverse event profile was "consistent with that of studies of other tyrosine kinase inhibitors in this indication and, as expected for this population of patients with breast cancer, with an anticipated poor outcome," Andre told attendees.
The poor response rates couldn't be chalked up to the drug not doing its job, as serum levels of markers of FGFR1 inhibition acted as expected.
One possibility was that the trial included patients who were just too advanced in their disease or too heavily pretreated to show a benefit, Andre suggested.
Patients had received no more than three lines of chemotherapy (70% got one or two lines in the metastatic setting) but at least one line of endocrine therapy for hormone-sensitive disease or at least one line of chemotherapy for hormone receptor-negative disease.
The patient population also frequently had multiple organ involvement (61% had at least three organs involved) with a high percentage of liver metastases (78%).
"Future trials are planned to include breast cancer patients with fewer prior treatments," Andre said.
The fibroblast growth factor receptor 1 (FGFR1) inhibitor dovitinib held clinical benefit for no more than 12% of patients without high expression of the target, Fabrice Andre, MD, PhD, of the Institut Gustave-Roussy in Villejuif, France, and colleagues found
The drug achieved stable disease or at least 50% tumor shrinkage at 24 weeks for 15% of patients with high levels of both FGFR1 and hormone receptors, the group reported here at the American Society of Clinical Oncology meeting.
Although these results weren't good enough for the phase II trial to move forward, Andre suggested it may be too early to give up on the drug entirely.
Antitumor activity couldn't be ruled out in the hormone receptor-positive, FGFR1-amplified group, he told attendees.
He pointed to a 25% rate of partial response that couldn't be confirmed or stable disease at 24 weeks in this small group.
Only 8% to 10% of breast cancers show amplification of FGFR1.
But those that do are often the poor prognosis, HER2-negative luminal B type of breast cancers that are associated with endocrine therapy resistance despite estrogen receptor expression, he noted.
Dovitinib inhibits FGFR1 along with other receptor tyrosine kinases and has been tested in melanoma and renal cell tumors.
Andre's group tested it in an open-label phase II trial among 68 patients with metastatic HER2-negative breast cancer.
Patients received 500 mg of oral dovitinib once a day in a five-day-on, two-day-off schedule.
Partial response by RECIST criteria at four to six weeks that could not be confirmed beyond that point was achieved by 15% of patients with FGFR1- and hormone receptor-positive disease (three of 21) but no patients in the other tumor subgroups.
Stable disease as the best response was seen in:
- 45% of the group positive for both FGFR1 and hormone receptor
- 48% of the FGFR1-negative, hormone receptor-negative group
- 24% of the group negative for both FGFR1 and hormone receptor
Median progression-free survival was 3.6, 3.5, and 2.1 months, respectively.
The adverse event profile was "consistent with that of studies of other tyrosine kinase inhibitors in this indication and, as expected for this population of patients with breast cancer, with an anticipated poor outcome," Andre told attendees.
The poor response rates couldn't be chalked up to the drug not doing its job, as serum levels of markers of FGFR1 inhibition acted as expected.
One possibility was that the trial included patients who were just too advanced in their disease or too heavily pretreated to show a benefit, Andre suggested.
Patients had received no more than three lines of chemotherapy (70% got one or two lines in the metastatic setting) but at least one line of endocrine therapy for hormone-sensitive disease or at least one line of chemotherapy for hormone receptor-negative disease.
The patient population also frequently had multiple organ involvement (61% had at least three organs involved) with a high percentage of liver metastases (78%).
"Future trials are planned to include breast cancer patients with fewer prior treatments," Andre said.
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