Issue No. 2 February 2007

Dear NOCR member,

What's New
Quick Poll
Industry News
Clinical Trials
New Clinical Trials
What's Next
Contact

• Last month’s issue introduced a new feature, Quick Poll, which will appear monthly during 2007. An interactive clinical question will be asked about a current topic or issue in oncology/hematology, much like the Pattern of Practice questions utilized in our live meetings. Rapid reporting of the voting results and a brief discussion will be posted on our Web site, www.asoncology.com, within 7-10 days to provide feedback for Network members. Please see the left-hand margin of this page for this month’s Quick Poll.

• Great Debates in Breast Cancer is scheduled for Friday, October 26 and Saturday, October 27, 2007 at the Wynn Las Vegas. Please mark your calendars with these dates now and visit our Web site, www.asoncology.com, for more details and online registration in the coming months. This is a CME-accredited educational activity.

• A series of six Oncology Highlights^SM meetings are scheduled for 2007. These CME-accredited events provide expert key opinion leader discussions of the most important clinically relevant abstracts presented at the 43^rd Annual Meeting of the American Society of Clinical Oncology in Chicago on June 1-5, 2007. The schedule for the highlights meetings is as follows: July 14 in New York, July 21 in Miami, July 28 in Chicago, August 4 in Las Vegas, August 11 in New York, and August 18 in San Francisco. We invite you to visit our Web site for additional information and online registration.

FDA Actions:

• On February 2, 2007 the FDA converted the approval of Pfizer’s sunitinib malate (Sutent^®) for the treatment of advanced renal cell carcinoma (RCC) from accelerated approval to regular approval following confirmation of an improvement in progression-free survival (PFS). The drug was originally granted accelerated approval for this indication in January 2006 based on partial response rates and response duration. The conversion to a regular approval is based on efficacy data demonstrated in a randomized clinical trial of 750 patients with treatment-naïve metastatic RCC comparing sunitinib to interferon-alfa therapy. An interim PFS analysis showed a median PFS of 47.3 weeks for sunitinib treated patients vs 22.0 weeks for IFN (HR 0.415 with p< 0.000001).

• Pharmion has received approval from the FDA for its new drug application supplement to add intravenous (IV) use as a new route of administration to the approved prescribing information for the company’s DNA demethylating agent azacitidine (Vidaza^®). With this approval, the drug may now be administered IV over a period of 10 to 40 minutes in a clinic or hospital setting. Dosing remains the same with IV administration as the previously approved subcutaneous route at 75 mg/m² daily, for 7 days, every 4 weeks. The approval is based on the existing clinical data from the original application, as well as additional data from an in-use stability and compatibility study and a pharmacokinetic modeling study recently completed. In 2004, Vidaza became the first drug approved by the FDA for the treatment of patients with myelodysplastic syndromes (MDS).

• The FDA has accepted Ortho Biotech Products’ supplemental new drug application (sNDA) for doxorubicin HCl liposome injection (Doxil^®) as combination therapy with bortezomib (Velcade^®) for the treatment of patients with multiple myeloma. The sNDA was filed based on the results of a planned interim analysis from a randomized phase III trial of 646 patients with relapsed or refractory myeloma (at least one prior Rx) who received either Doxil plus Velcade or Velcade alone. Pts treated with the combination had 45% less risk of their disease progressing and a statistically significant improvement in median time-to-progression (TTP).

• GlaxoSmithKline (GSK) has received notice that the FDA has issued an approvable letter for the company’s once-daily anticoagulant, fondaparinux (Arixtra^®), for treating patients with acute coronary syndromes (ACS). The company hopes to receive approval of Arixtra for treating patients with unstable angina or non-ST segment elevation MI. In October 2006 the FDA granted priority review to the sNDA for the ACS treatment indication. The submission was based on results from the OASIS-5 trial that compared Arixtra with enoxaparin (Lovenox^®) in patients with unstable angina and non-ST elevation MI which demonstrated that the two drugs were similar in reducing the risk of ischemic events, but Arixtra substantially reduced major bleeding and improved long-term mortality and morbidity compared to Lovenox (NEJM 2006;354:1464-1476.). (Back)

• On February 12, 2007 Bayer Pharmaceuticals and Onyx Pharmaceuticals announced that an independent data monitoring committee (DMC) has reviewed the safety and efficacy data from the companies’ pivotal phase III trial (the SHARP trial) in 602 patients with advanced hepatocellular carcinoma (HCC) randomized to receive either sorafenib (Nexavar®) or placebo. This planned interim analysis of data demonstrated that the trial met its primary endpoint resulting in superior, significant overall survival (OS) in those patients receiving sorafenib vs those receiving placebo. There was no demonstrated difference in serious adverse event rates between the two treatments. Based on these conclusions, the DMC recommended that the trial be stopped early. The companies will stop the trial and allow all patients enrolled in the trial access to sorafenib. The companies continue discussions with both the FDA and European health authorities regarding the next steps in filing for approval for the treatment of HCC. They plan to sub it the results from the trial to the American Society of Clinical Oncology (ASCO) for presentation at its annual meeting June 1-5, 2007.

• On January 24, 2007 the National Cancer Institute (NCI) released positive results of a phase III clinical trial demonstrating that adult patients with untreated acute promyelocytic leukemia (APL) who had standard chemotherapy to induce remission of their disease, and then received arsenic trioxide (Trisenox^®, Cephalon) to maintain remission, had significantly better event-free survival (EFS) and better OS than those who received only standard chemotherapy. The trial was sponsored by the NCI and was led and coordinated by the Cancer and Leukemia Group B (CALGB). The study tested the efficacy and toxicity from adding two 25-day courses of IV arsenic trioxide to the standard combination of ATRA and chemotherapy. Five hundred eighty-two patients were randomized to receive standard Rx or the same standard Rx plus arsenic trioxide (the experimental combination arm). Results: The percentage of patients who remained alive and in remission – free of relapse of their leukemia – 3 years after diagnosis was 77% on the combination compared to 59% on the standard Rx arm. The difference was highly statistically significant. The more effective combination arm also resulted in better OS after 3 years at 86% vs 77% for patients in the standard Rx arm. The patients were followed for a median period of 29 months. These positive results are being released so that all APL patients will have a chance to benefit from this therapy. A complete scientific presentation of these study results is planned for the annual meting of ASCO in June 2007.

• An interim analysis of the XCALIBr (Xeloda in Combination with Avastin as First-Line Treatment for HER2-Negative Metastatic Breast Cancer) trial suggested that first-line therapy with oral capecitabine (Xeloda^®, Roche) in combination with bevacizumab (Avastin^®, Genentech) may offer clinical benefit in metastatic breast cancer (MBC) patients who have no prior treatment. These data were presented at the 29th Annual San Antonio Breast Cancer Symposium (SABCS). The primary objective was to evaluate progression-free survival (PFS). The interim analysis of 103 patients demonstrated that 42.7% remained progression-free on first-line Rx with the combination while 20% had progressed requiring second-line therapy after a median duration of 4.2 months. Treatment with the combination regimen produced a 72% clinical benefit (response rate + stable disease) with 5% CR + 29% PR = 34% overall RR; another 38% of patients had stable (non-progressed) disease. This combination was well tolerated in most patients. The most common grade 3 adverse events were HFS (13%) and pain (10%). (Back)

• Biogen Idec has initiated a randomized, controlled registration trial of an investigational anti-CD23 monoclonal antibody, lumiliximab, for patients with chronic lymphocytic leukemia (CLL). The phase II trial will compare treatment with lumiliximab in combination with fludarabine, cyclophosphamide, and rituximab (FCR) with FCR alone in patients whose CLL has relapsed or failed to respond to initial Rx. Lumiliximab was granted fast-track and orphan drug designation by the FDA for the CLL indication. The newly initiated registration study, the LUCID trial, will enroll 276 patients worldwide. CD23 is highly expressed on B-CLL cells. The primary objective is to compare the clinical benefit of each treatment arm in relapsed CLL patients. The primary endpoint is complete response rate, a predictor of PFS in CLL patients. Phase I/II study data of the monoclonal antibody presented in December 2006 demonstrated that when added to FCR, lumiliximab achieved a 52% CR rate in patients whose CLL had progressed after prior therapy.

• GlaxoSmithKline (GSK) has initiated an international breast cancer clinical trial to evaluate the use of lapatinib (Tykerb^®) in the adjuvant therapy of early breast cancer (BC). The TEACH (Tykerb Evaluation After CHemotherapy) trial will be the first phase III study to investigate whether adjuvant Rx with lapatinib will improve disease-free survival (DFS) in women with early stage HER2-positive BC, including those with positive and negative node involvement. Approximately 3,000 women will be enrolled in more than 30 countries. The trial is designed to compare the efficacy and safety of lapatinib vs placebo in women treated for early stage, HER2-positive BC who have no clinical or radiographic evidence of disease. Participants must have completed primary adjuvant chemotherapy but must not have received trastuzumab. Patients will be randomized to receive lapatinib 1,500 mg or matching placebo orally once/day for a maximum of 12 months or until disease recurrence. All women will be followed until death or until study closure.
  

Contact
The American School of Oncology™
4325 Alexander Drive
Alpharetta, Georgia
30022-3740 USA
www.asoncology.com
reply@asoncology.com

Next issue of OncoFacts™ will be in March 2007 and then monthly throughout the year.

OncoFacts™ Editor:

Jim Jones, MD

For ongoing improvement, we would appreciate your comments and suggestions.
E-mail your suggestions to: reply@asoncology.com.

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