Pfizer Inc. (NYSE: PFE) today announced results from studies evaluating
neratinib (HKI-272), an investigational, orally administered, pan-ErbB
inhibitor, in patients with human epidermal growth factor receptor-2
(HER2, also known as ErbB2) positive breast cancer at the 2009 CTRC-AACR
San Antonio Breast Cancer Symposium (SABCS). Neratinib is now part of
Pfizer’s expanded oncology portfolio, following the recent acquisition
of Wyeth.
“Data gathered from ongoing clinical trials of neratinib, both as a
monotherapy and in combination, continue to support its evaluation in
HER2 positive metastatic breast cancer,” said Maria Koehler MD, PhD,
Vice President, Women’s Cancers Strategy for Pfizer Oncology. “We look
forward to studying neratinib further in an effort to help seek to
provide HER2 targeted therapies for patients battling this aggressive
disease.”
Breast cancer of the HER2 positive type accounts for 20 to 30 percent of
all breast cancers and is identified by the overexpression of the HER2
protein in tumor tissue. HER2 positive breast cancer is more aggressive
than other breast cancers and has an increased likelihood of
metastasizing.
Neratinib Shows Activity in Phase 1/2 Study
This ongoing, Phase 1/2, open-label, two-part study evaluates the safety
and efficacy of neratinib in combination with weekly paclitaxel in
patients with solid tumors and HER2 positive metastatic breast cancer
(Poster #5081). Part 1 of the study showed that a standard oral dose of
240 mg of neratinib daily can be given with 80 mg/m2 of
paclitaxel weekly to patients with solid tumors. In part 2, only
patients with HER2 positive metastatic breast cancer (newly diagnosed or
following up to three recurrences) received therapy to evaluate the
overall response rate (ORR) of this combination of neratinib and
paclitaxel.
As of October 19, 2009, an ORR (including both complete and partial
responses) of 69 percent>
In part 2 of the study, preliminary clinical data indicate the
combination of neratinib 240 mg and paclitaxel 80 mg/m2 was
tolerable, with a similar toxicity profile to each drug given as
monotherapy. The most common treatment-emergent adverse events occurring
in ≥20 percent of patients included diarrhea, neutropenia, alopecia,
peripheral neuropathy, leucopenia, infection (any site), anemia, rash,
nausea, vomiting, fatigue, anorexia and pyrexia. Diarrhea of any grade
was the most common adverse event (in 91 percent of patients), and
presented as a grade 3/4 adverse event in 28 percent of patients.
Diarrhea was generally observed early (median onset, three days after
the first dose of neratinib; median duration, 30 days). Fifteen and 37
patients required dose reductions of neratinib and paclitaxel,
respectively, because of adverse events, and a total of 49 patients
discontinued the study. Most study discontinuations (39 patients) were
secondary to disease progression. Three patients discontinued therapy
due to adverse events (renal failure, left ventricular ejection fraction
reduction, and mouth ulceration).
Phase 2 Safety Results of Neratinib Monotherapy in Patients with HER2
Positive Breast Cancer