New Data Evaluating Sutent, CP-751,871 and Axitinib in Patients with Non-Small Cell Lung Cancer
"Pfizer is committed to developing innovative treatments for people with non-small cell lung cancer, the leading cause of cancer death in the United States," said Charles Baum, MD PhD, head of oncology development at Pfizer. "We are encouraged by the positive data presented today, which support our multi-faceted approach to targeting cancer cells."
Sunitinib malate Data
New data were presented from a phase II study demonstrating the anti-tumor activity of sunitinib malate, a multi-kinase inhibitor with anti-angiogenic and anti-proliferative activity. The study examined the safety and efficacy of single-agent sunitinib malate (37.5 mg/day given on a continuous dosing schedule), in 47 previously treated patients with advanced, recurrent NSCLC, who had received one to two prior chemotherapy regimens. The objective response rate was 2.1 percent. 17 percent of patients had stable disease, and observed median overall survival was 37.1 weeks. The study also showed median progression-free survival of 12.3 weeks, and demonstrated a tolerable safety profile. Most common adverse events included fatigue, dyspnea and diarrhea.
These findings further support the rationale for evaluating the role of sunitinib malate in advanced NSCLC in a phase III program which Pfizer plans to initiate later this year.
Also presented was an interim analysis of an ongoing, phase II, randomized, non-comparative, multi-center study of CP-751,871. This study evaluated 73 patients with late-stage NSCLC. 46 percent of patients treated with CP-751,871 combined with standard care (paclitaxel and carboplatin) achieved an objective response -- meaning the tumor either partially or completely disappeared. In a subset of patients with non-adenocarcinoma (a form of NSCLC), 52 percent of those receiving the combination of CP-751,871, paclitaxel and carboplatin had objective responses. Approximately one-third (32 percent) of patients receiving paclitaxel and carboplatin alone had objective responses. CP-751,871 was well tolerated as a single agent and in combination with paclitaxel and carboplatin; the most common adverse events were hyperglycemia, fatigue, neutropenia, and neuropathy. CP-751,871 is part of a treatment approach known as signal transduction, which blocks specific cellular signals important to cancer cell growth and survival. CP-751,871 targets and inhibits signaling on the IGF-1R pathway.
"Non-small cell lung cancer is a complex cancer with limited treatment options," said Daniel Karp, MD, Professor of Thoracic/Head & Neck Medical Oncology at the University of Texas, MD Anderson Cancer Center. "It is very exciting to be working with this new class of compounds targeted at what appear to be a critical pathway in the development of lung cancer. The data presented at ASCO on CP-751,871 support further research in an effort to expand the range of therapies available to physicians, allowing them to better tailor their treatment approach to each individual patient."
Promising results were also seen with axitinib, an oral and selective inhibitor of VEGFR 1, 2, 3 (vascular endothelial growth factor receptors 1, 2, 3). An open-label, multi-center phase II study evaluated the efficacy and safety of axitinib in 32 patients with advanced NSCLC, 78 percent of whom had received prior chemotherapy. Axitinib demonstrated activity as a single agent with an objective response rate of 9 percent and median overall survival of approximately 15 months. Axitinib was also well-tolerated in this population. The most common adverse events were fatigue, anorexia, diarrhea and hypertension. Axitinib is part of the therapeutic approach known as anti-angiogenesis, which means it works by inhibiting blood vessel formation, thereby starving tumors of blood and nutrients needed for growth.
The company is also developing PF-3512 676, a novel immunotherapeutic based on Toll-Like Receptor 9 agonism. Of the agents Pfizer is investigating for NSCLC, this is in the most advanced stage of development. Data is not being presented at ASCO but accrual of two phase III clinical trials was recently completed.
PF-676 is a toll-like receptor (TLR) 9 agonist, which stimulates dendritic cells to trigger a cytokine and chemokine cascade and subsequent T-cell activation. Two phase III clinical trials of PF-676, one with paclitaxel plus carboplatin, the other with gemcitibine plus cisplatin, began recruiting patients in November 2005 and completed accrual in April 2007. These studies are international, multi-center, open-label, two-arm, randomized phase III trials. The total enrollment for each study is approximately 800 patients.
About SUTENT(R) (sunitinib malate)
SUTENT is a multi-kinase inhibitor approved for the treatment of advanced renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate.
Women of child bearing age who are (or become) pregnant during therapy should be informed of the potential for fetal harm while on SUTENT.
Decreases in left ventricular ejection fraction (LVEF) to below the lower limit of normal (LLN) have been observed. Patients with concomitant cardiac conditions should be carefully monitored for clinical signs and symptoms of congestive heart failure.
Patients should be monitored for hypertension and treated as needed with standard antihypertensive therapy. CBCs with platelet count and serum chemistries should be performed at the beginning of each treatment cycle for patients receiving treatment with SUTENT.
In an ongoing clinical trial of patients with metastatic non-small cell lung cancer (NSCLC), fatal pulmonary hemorrhage occurred in two patients, both with squamous cell histology. SUTENT is not approved for use in patients with NSCLC.
The most common adverse reactions are fatigue, asthenia, diarrhea, nausea, mucositis/stomatitis, vomiting, dyspensia, abdominal pain, constipation, hypertension, rash, hand-foot syndrome, skin discoloration, altered taste, anorexia and bleeding.
For more information on SUTENT and Pfizer Oncology please visit www.pfizer.com.
DISCLOSURE NOTICE: The information contained in this release is as of June 2, 2007. Pfizer assumes no obligation to update any forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about various products in development, including their potential benefits, that involves substantial risks and uncertainties. Such risks and uncertainties include, among other things, the uncertainties inherent in research and development; decisions by regulatory authorities regarding whether and when to approve any drug applications that may be filed for any such products in development as well as their decisions regarding labeling and other matters that could affect their availability or commercial potential; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer's Annual Report on Form 10-K for the fiscal year ended December 31, 2006 and in its reports on Form 10-Q and Form 8-K.
Vanessa Aristide, 212-733-3784
Jennifer Torres, 917-921-4458
Posted: June 2007
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