Pfizer Inc. will present more than 30 abstracts, including data from investigational compounds, axitinib, crizotinib, and bosutinib, as well as data evaluating Sutent (sunitinib malate), across multiple tumour types, at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago from June 3-7. The company will also share analyses from early stage compounds focused on the science behind tumour growth.
“The research we are presenting at ASCO represents Pfizer’s continued commitment to finding novel treatment solutions and improving the lives of patients with cancer,” said Dr Mace Rothenberg, senior vice president of clinical development and medical affairs for Pfizer’s Oncology Business Unit. “We are excited to present data demonstrating the efficacy and tolerability of several of our late-stage compounds, while also highlighting early phase clinical research exploring key mechanisms and promising pathways which may help inspire new potential therapeutic approaches for many difficult to treat cancers.”
Pfizer is presenting results from the phase III AXIS 1032 trial, comparing axitinib to sorafenib in patients with previously-treated advanced Renal Cell Carcinoma (RCC). These are the first pivotal head-to-head data comparing active, targeted therapies in advanced RCC (Oral presentation, Abstract #4503, June 6). In addition, two other axitinib RCC abstracts will be presented.
Patient-Reported Outcomes (PRO) from the AXIS 1032 trial (Oral presentation, Abstract #4504, June 6)
Five-year overall survival data from a phase II trial of axitinib as a second-line treatment for patients with metastatic RCC (Poster discussion, Abstract 4547, June 7)
Axitinib is an oral and selective inhibitor of Vascular Endothelial Growth Factor (VEGF) receptors 1, 2 and 3,1 receptors that can influence tumour growth, vascular angiogenesis and progression of cancer (the spread of tumours).
At ASCO, Pfizer will publicly present for the first time data from an early stage study demonstrating the impact of crizotinib, an oral, first-in-class compound that inhibits the anaplastic lymphoma kinase, or ALK, compared to historical controls, on overall survival in patients with advanced ALK-positive non-small cell lung cancer (NSCLC) (Oral presentation, Abstract 7507, June 5).
Updated Progression-Free Survival (PFS) from a part II expansion cohort of a phase I study in patients with ALK-positive advanced NSCLC (Clinical Science Symposium, Abstract 2501, June 3).
Initial phase II results of crizotinib in advanced ALK-positive NSCLC (Poster discussion, Abstract #7514, June 6).
Pfizer continues to investigate the potential of targeting specific pathways in haematologic malignancies, and will provide an update on clinical trials of bosutinib as a single agent in both newly diagnosed3 and previously treated patients with Philadelphia chromosome positive (Ph+) Chronic Phase (CP) Chronic Myeloid Leukaemia (CML).
18-month follow up data from the Bosutinib Efficacy and safety in chronic myeloid LeukemiA [BELA] phase III study evaluating bosutinib as a first-line treatment in patients with CP CML (Poster discussion, Abstract #6509, June 3).
Bosutinib as third-line therapy for CP CML patients following failure of or intolerance to imatinib and dasatinib or nilotinib (Study 200) (Abstract #6535, June 6).
Health-related quality of life in newly diagnosed (Abstract #6612, June 6)14 and imatinib-resistant or imatinib intolerant CP CML patients (Abstract #6620, June 6).
Bosutinib is an investigational oral dual Src and Abl kinase inhibitor with minimal inhibitory activity against c-kit and PDGFR.16 It is believed that by dual inhibition of the Src and Abl tyrosine kinases, bosutinib may inhibit signaling in CML cells that allows the cells to grow, survive and reproduce.17
Since its approval in 2006, Sutent has changed the treatment landscape for advanced RCC and imatinib-resistant or -intolerant Gastrointestinal Stromal Tumours (GIST) and remains a standard of care in these indications.
In November 2010, Sutent was approved in Europe for the treatment of unresectable or metastatic, well-differentiated pancreatic Neuro-Endocrine Tumours (NET) with disease progression in adults. Experience with Sutent as first-line treatment is limited. Sutent is currently under review by the US FDA for the treatment of unresectable pancreatic NET.
At ASCO, Pfizer will present new analyses from trials evaluating Sutent in patients with advanced unresectable pancreatic NET4 and in patients with metastatic RCC.
Updated overall survival and progression-free survival data by Blinded Independent Central Review (BICR) of sunitinib versus placebo for patients with advanced unresectable pancreatic NET (Poster discussion, Abstract #4008, June 6).
Circulating protein biomarkers of sunitinib and interferon-a efficacy in treatment-naïve patients with metastatic RCC (Poster discussion, Abstract 10525, June 4).
A pooled analysis of the efficacy and safety of sunitinib in elderly patients with metastatic renal cell carcinoma (mRCC) (Abstract #4604, June 5). Additionally at ASCO, results from phase III studies of sunitinib in metastatic Castration-Resistant Prostate Cancer (mCRPC) and advanced hepatocellular carcinoma (HCC)20 will be presented.
Pfizer announced last year that these studies did not meet their primary endpoints.
Phase III trial of sunitinib with prednisone versus prednisone alone in mCRPC (Oral presentation, Abstract 4515, June 6).
Phase III trial of sunitinib versus sorafenib in advanced HCC (Oral presentation, Abstract 4000, June 7).
Pfizer will present data from its early stage pipeline evaluating multiple compounds targeting innovative pathways.
Phase I study of PF-04554878, a Focal Adhesion Kinase (FAK) inhibitor, in patients with advanced solid tumours (Clinical Science Symposium, Abstract 3002, June 5).
Phase I study of PF-03446962, a fully human monoclonal antibody (mAb) against activin receptor-like kinase 1 (ALK-1), a TGFß receptor involved in tumour angiogenesis (Oral presentation, Abstract #3009, June 5)
Randomized phase II study of PD 0332991, a Cyclin-Dependent Kinase (CDK) 4/6 inhibitor, in combination with letrozole for first-line treatment of patients with post-menopausal, estrogen receptor positive, HER2-negative advanced breast cancer (Abstract #TPS100, June 6).
Data on the following compounds and investigational agents will also be presented: Torisel (temsirolimus) (mantle cell lymphoma), neratinib (breast cancer), PF-00299804 (head and neck cancer), figitumumab (colorectal cancer), tremelimumab (pancreatic cancer), gamma secretase inhibitor – PF-03084014 (solid tumours), PARP (poly ADP ribose polymerase) inhibitor – PF-01367338 (peripheral blood lymphocytes), dual angiopoietin-2 (Ang2) and VEGF inhibitor – CVX-241 (solid tumours).
Sutent is an oral multi-kinase inhibitor that works by blocking multiple molecular targets implicated in the growth, proliferation and spread of cancer. Two important Sutent targets, VEGFR and Platelet-Derived Growth Factor Receptor (PDGFR) are expressed by many types of solid tumours and are thought to play a crucial role in angiogenesis, the process by which tumours acquire blood vessels, oxygen and nutrients needed for growth. Sutent also inhibits other targets important to tumour growth, including KIT, FLT3 and RET.
Hepatotoxicity has been observed in clinical trials and post-marketing experience. This hepatotoxicity may be severe, and deaths have been reported. It is recommended to monitor liver function tests before initiation of treatment, during each cycle of treatment, and as clinically indicated. Sutent should be interrupted for Grade 3 or 4 drug-related hepatic adverse events and discontinued if there is no resolution. Sutent should not be restarted if patients subsequently experience severe changes in liver function tests or have other signs and symptoms of liver failure.
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. Complete Blood Counts (CBCs) with platelet count and serum chemistries should be performed at the beginning of each treatment cycle for patients receiving treatment with Sutent.
The most common adverse reactions in GIST, RCC and pancreatic NET clinical trials were diarrhoea, fatigue, asthenia, nausea, mucositis/stomatitis, anorexia, vomiting, neutropenia, hypertension, dyspepsia, abdominal pain, constipation, rash, hand-foot syndrome, skin discoloration, hair colour changes, altered taste and bleeding.
Torisel is the only intravenous mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of advanced Renal Cell Carcinoma (RCC).
Based on preclinical studies, Torisel inhibits the activity of mTOR, an intracellular protein implicated in multiple growth-related cellular functions including proliferation, growth and survival. The inhibition of mTOR also reduces levels of certain growth factors, such as VEGF, which are overexpressed in solid tumours like kidney cancer and are thought to play a crucial role in angiogenesis, the process by which tumours acquire blood vessels, nutrients and oxygen needed for growth.
Torisel is contraindicated in patients with bilirubin >1.5 times the Upper Limit of Normal (ULN). If Torisel must be given to patients with mild hepatic impairment, it should be used with caution and at a reduced dose.
Torisel has been associated with serious and sometimes fatal side effects including: hypersensitivity reactions, hyperglycemia/glucose intolerance, infections, interstitial lung disease, hyperlipidemia, bowel perforation, renal failure, wound healing complications, and intracerebral haemorrhage.
Live vaccines and close contact with those who received live vaccines should be avoided. Women of childbearing potential should be advised of the potential hazard to the foetus and avoid becoming pregnant.
The most common adverse reactions (incidence = 30%) are rash, asthenia, mucositis, nausea, edema, and anorexia. The most common laboratory abnormalities (incidence = 30%) are anaemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, elevated alkaline phosphatase, elevated serum creatinine, lymphopenia, hypophosphatemia, thrombocytopenia, elevated AST, and leucopenia.
Strong inducers of CYP3A4/5 and inhibitors of CYP3A4 may affect concentrations of the primary metabolite of Torisel. If alternatives cannot be used, dose modifications of Torisel are recommended.
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