A combination of PB272 (neratinib) and Kadcyla (ado-trastuzumab emtansine) may benefit HER2-positive metastatic breast cancer patients who previously received chemotherapy and another combo treatment, a clinical trial indicates.
Results of the FB-10 Phase 1b/2 trial (NCT02236000) revealed that 56 percent of patients saw their tumor shrink or disappear after the combo treatment. The patients had previously received chemo plus a combination of Herceptin (trastuzumab) and Perjeta (pertuzumab).
Patients were also able to tolerate the PB272-Kadcyla combo, the trial indicated.
The findings were presented at the American Association for Cancer Research (AACR) 2017 Annual Meeting in Washington April 1-5. The oral presentation was titled “NSABP FB-10: Phase Ib dose-escalation study evaluating trastuzumab emtansine (T-DM1) with neratinib in women with metastatic HER2-positive breast cancer.”
“We are pleased to see the high response rate of the combination of T-DM1 and neratinib in this patient population who were previously treated with both pertuzumab and trastuzumab,” Alan H. Auerbach, chief executive officer and president of Puma Biotechnology, said in a press release. “We look forward to completing enrollment in the current cohort and moving this combination into Phase 2 trials.”
PB272 is an irreversible tyrosine kinase inhibitor that Puma is developing as an oral treatment for patients with HER2-positive breast cancer. A Phase 2 clinical trial whose results were published in 2010 showed that PB272 by itself benefits HER-positive metastatic breast cancer patients.
While response rates and progression-free survival rates were better in patients who had not received doses of Herceptin, the treatment also worked in patients who had.
Kadcyla is an antibody-drug conjugate that uses the trastuzumab antibody to deliver a cytotoxic agent to cancer cells.
The FB-10 study is now evaluating the safety, tolerability, and preliminary effectiveness of the PB272-Kadcyla combination in patients who received previous chemotherapy plus Herceptin and Perjeta.
Patients received one of four dose-escalating cohorts of PB272 — 120, 160, 200, or 240 mg per day. They received Kadcyla on the first day of each 21-day cycle.
Among the 16 patients whom researchers were able to evaluate for the combo’s effectiveness, 56 percent responded. The breakdown was 19 percent complete responses, and 37 percent partial responses.
The most severe adverse events included diarrhea, nausea, hypertension, and low blood platelet numbers.
The company is recruiting additional patients for the 160-mg cohort so it can define a recommended Phase 2 dose.
“We are encouraged by these initial findings, and we will continue to enroll patients at the 160-mg dose to further evaluate the impact in this patient population,” said Dr. Jame Abraham, the principal investigator of the study. He is director of the Breast Oncology Program at Taussig Cancer Institute and a professor of Medicine at the Cleveland Clinic.
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