By Elizabeth Whittington

FDA OKs Tarceva Combo for Pancreatic Cancer

Tarceva® (erlotinib), initially approved for non-small cell lung cancer, has been granted a second indication by the Food and Drug Administration after showing benefit in advanced pancreatic cancer. Used in combination with Gemzar® (gemcitabine), Tarceva is now approved for first-line treatment of locally advanced, inoperable or metastatic pancreatic cancer.

Tarceva is the first approved therapy for advanced pancreatic cancer in almost a decade, and its approval was greatly anticipated because pancreatic cancer has few optimal treatments and often has a short survival time. Pancreatic cancer, one of the most aggressive cancers, has an average survival rate of three to six months once the cancer has spread.

Prior to Tarceva’s approval, Gemzar had been the standard treatment for advanced pancreatic cancer either alone or combined with other drugs in clinical trials. Other targeted agents and conventional chemotherapies had not had much success in pancreatic cancer, but Tarceva in combination with Gemzar showed an increase in one-year survival and progression-free survival. In a randomized phase III trial, patients with previously untreated advanced pancreatic cancer had a one-year survival rate of 24 percent with the combination regimen compared with 19 percent for those patients taking Gemzar alone—a 23 percent relative improvement. Common side effects included rash, fatigue, nausea and diarrhea.

Tarceva is an oral tyrosine kinase inhibitor that interferes with cell growth by inhibiting the epidermal growth factor receptor (EGFR). Overexpression of EGFR is common in many cancer types in addition to lung and pancreatic, including head and neck and colorectal cancers. Tarceva is also being tested in kidney cancer, ovarian cancer, mesothelioma and an aggressive type of brain cancer called glioblastoma multiforme. For details, visit www.tarceva.com.

Panitumumab Pummels Metastatic Colorectal Cancer

A phase III international study in metastatic colorectal cancer showed intravenous panitumumab (ABX-EGF) improved progression-free survival and response rates in patients whose cancer was resistant to standard chemotherapy. Comparing panitumumab with best supportive care, the monoclonal antibody produced a 46 percent decrease in tumor progression, which was greater than the 33 percent decrease researchers expected. The most common side effects with panitumumab are mild rash, fatigue and diarrhea. Overall survival data will be available in late 2006.

Granted fast-track status in July 2005, panitumumab binds with EGFR and inhibits tumor cell growth. Because EGFR is overexpressed in as many as 77 percent of colorectal cancers, it is a prime target for anti-cancer therapies, including monoclonal antibodies. Currently only one monoclonal antibody is approved for metastatic colorectal cancer, Erbitux® (cetuximab), which contains both human and mouse antibodies. Unlike Erbitux, panitumumab is a fully human antibody that eliminates the allergic reaction that occurs in 3 percent of patients taking Erbitux. Panitumumab can also be administered less frequently—every other week compared with Erbitux’s weekly regimen.

The FDA is expected to review panitumumab for treatment of metastatic colorectal cancer in 2006. It is also being considered in other cancers such as head and neck cancer. Panitumumab is currently being studied as both a single agent and in combination with the targeted agent Avastin® (bevacizumab). For more about panitumumab clinical trials, visit www.amgentrials.com.

Newer, Stronger Agent for Lung Cancer

A current standard chemotherapy combination for non-small cell lung cancer (NSCLC) is Taxol® (paclitaxel) and Paraplatin® (carboplatin). But in a recent phase I/II trial, patupilone showed benefit in patients with refractory or recurrent advanced NSCLC. Patupilone is an epothilone, a class of agents that work in a similar manner to taxanes, such as Taxol and Taxotere® (docetaxel). Both classes induce cell death, but epothilones are more potent.

In preclinical studies, epothilones have been effective in taxane-resistant NSCLC. A phase I/II study of patupilone reported an overall response rate of 46 percent, with a partial response occurring in five patients and disease stabilization in 16 patients. All 46 evaluable patients in the trial had received prior treatment with carboplatin or cisplatin, and nearly a third also had prior taxane therapy.

The most common side effects with patupilone were diarrhea and weakness. The trial established that patupilone given every three weeks had few side effects and produced a tumor response in nearly half of patients, including patients whose cancer recurred after standard chemotherapy. The phase II portion of the trial is ongoing.

The drug has shown benefit as a single agent in cancers of the breast, colon, prostate and ovary in preclinical studies, and researchers are also studying patupilone in combination with carboplatin. For more, visit www.novartisoncology.com.

Drug Update

CURE wants to keep you updated on items previously discussed in Drugs in the News...

Exjade Approved as First Oral Iron Chelator

Exjade® (deferasirox), a daily oral tablet that is dissolved in water or juice, received accelerated approval from the FDA in November for iron chelation. Patients who must undergo frequent blood transfusions, such as with myelodysplastic syndromes, may develop a life-threatening overabundance of iron. Chronic iron overload can cause liver failure, heart failure and diabetes. Side effects of Exjade include diarrhea and increased serum creatinine levels, which can signify kidney problems.

Arranon Approved for Rare Leukemia

The FDA granted accelerated approval in October to Arranon® (nelarabine), an effective drug against T-cell acute lymphoblastic leukemia, or T-ALL, in adults and children. Arranon is inactive until converted to its active, toxic form that inhibits cell growth and division. Side effects may include reduced blood counts, fatigue and infection. For more on Arranon, visit www.gsk.com.

HPV Vaccine Filed for Approval

Merck submitted a biologics license application (BLA) for Gardasil® to the FDA in early December. The drug company is seeking priority review for the cervical cancer vaccine, which means the FDA would review and act on the filing within six months of receipt as opposed to the standard 10 months. In a phase III trial, Gardasil prevented 100 percent of cervical pre-cancers and non-invasive cervical cancers associated with human papillomavirus (HPV) types 16 and 18, which combined account for approximately 70 percent of cervical cancer cases. The vaccine also protects against HPV types 6 and 11, which combined account for about 90 percent of genital wart cases. For more information, visit www.merck.com.