Issue No. 1 January 2007

Dear NOCR member,
Best wishes for a prosperous, Happy New Year!!

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

• A new feature will debut in this issue: Quick Poll. Each month an interactive clinical question will be asked about a current topic 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.

• Our 13th Annual Oncology Meeting will be held on Friday, February 16 and Saturday, February 17, 2007 at the Four Seasons Hotel in Las Vegas, Nevada. This CME accredited activity will include discussions of current issues in the major solid tumors and the hematologic malignancies by a carefully selected faculty of national thought leaders. Special sessions to be presented are Milestones of Oncology – “Events that Changed the Course of Cancer Therapy and Implications for the Future”, “Washington Update” on legislative issues, and a keynote address – “Tumor Stem Cells in Oncology”. We invite you to visit our Web site at www.asoncology.com for more information and to register online.

• The Hematology Highlights^SM and Breast Cancer Highlights^SM series provide expert key opinion leader discussions of the most important abstracts presented at the December 2006 American Society of Hematology Annual Meeting and the San Antonio Breast Cancer Symposium. The fourth and final Hematology Highlights^SM meeting is scheduled for February 3, 2007 in San Francisco. Remaining Breast Cancer Highlights^SM meetings are scheduled for February 3 in New York and February 10 in Chicago. You may visit our Web site at www.asoncology.com for more information and online registration.(Back)

• The Associated Press reported on January 17, 2007 that cancer deaths in the United States have declined for the second straight year, according to officials at the American Cancer Society in Atlanta, Georgia. A decline of 369 deaths from 2002 to 2003 was the first annual decrease in total cancer deaths in this country since 1930. This information, determined by a review of US death certificates by the American Cancer Society, was reported last year. Since the decline was so slight, experts were hesitant to say whether it was real or just a statistical fluke. However, the decrease from 2003 to 2004 was 3,014 fewer cancer deaths – more than eight times greater than the 2002 to 2003 decline.

• Experts are attributing the success to declines in smoking and to the earlier detection and more effective treatment of cancer. These have resulted in a fall in the death rates for breast, prostate, and colorectal cancer. The lung cancer death rate in men has been falling, but the female rate has reached a plateau. The largest drop in deaths among the major cancers was in colorectal cancer, which decreased by 1,110 in men and by 1,094 in women. Colon cancer screening is the major factor in the colon cancer mortality decline, but more effective treatments in recent years will have an impact as well. The American Cancer Society has projected that more than 1.4 million new cases of cancer and 559,650 cancer deaths will occur this year.(Back)

FDA Actions:

• On December 8, 2006 the FDA granted approval to Millennium Pharmaceuticals’ bortezomib (Velcade®), a proteasome inhibitor, for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. The approval is based upon data from the PINNACLE trial, a single-arm, multicenter study designed to assess response rate and duration of response in patients (N=155) with progressive MCL who had received at least one prior therapy. Patients (pts): 75% had 1 or more extranodal sites, 77% stage IV; 91% prior Rx with CHOP-like chemo. + rituximab and 37% refractory to last prior Rx. Results: Overall response rate, (CR + CRu + PR) was 31% with CR + CRu of 8% and median response duration of 15.4 months. Median time to response was 40 days.

• The FDA has accepted and granted priority review status to Wyeth Pharmaceuticals’ new drug application (NDA) for temsirolimus (Torisel™) to be used in the treatment of patients with advanced renal cell carcinoma (RCC). The FDA previously granted fast track designation and orphan drug status for the experimental drug for this indication. Temsirolimus is an mTOR (mammalian target of rapamycin) inhibitor that specifically inhibits the mTOR kinase that regulates cell proliferation, cell growth, and cell survival. The NDA contains interim data from a three-arm phase III trial of 626 pts with advanced RCC who had not received prior systemic Rx. Results showed that temsirolimus significantly increased overall survival (OS) by 49% compared to pts treated with interferon-alpha. The drug will be available in the US prior to FDA approval through an Expanded Access Program (EAP).

• Pharmacyclics, Inc. has submitted a NDA to the FDA for motexafin gadolinium (Xcytrin®) seeking approval to market the product for the treatment of NSCLC pts with brain metastases. The company submitted the pooled analysis of two phase III trials evaluating the safety and efficacy of whole brain radiation therapy (WBRT) alone to WBRT plus Xcytrin in 805 NSCLC pts with brain metastases. Primary endpoint was time to neurologic progression (TNP). Median TNP was 15.4 months for WBRT + Xcytrin vs 9.0 months for WBRT alone (p=0.016; HR=0.73). Xcytrin has a novel mechanism of action that is designed to selectively concentrate in tumors and induce apoptosis. In the trials it was well tolerated and did not interfere with the ability to deliver WBRT. It has been granted fast-track designation for the indication by the FDA.

• The FDA has assigned priority review status to Dendreon’s biologics license application (BLA) for sipuleucel-T (Provenge®), an experimental active cellular immunotherapy for the treatment of patients with asymptomatic, metastatic, androgen-independent (hormone-refractory) prostate cancer. The BLA submission is based primarily on the results of a phase III trial (D9901) that demonstrated a statistically significant 4.5 month improvement in OS in pts receiving Provenge vs those given a placebo (median 25.9 vs 21.4 months; p=0.01); these patients had a 41% overall reduction in the risk of death. At 36 months after treatment, the estimated survival rate in pts receiving Provenge was 34% compared to 11% for placebo pts. The drug is designed to stimulate the patients T-cell immunity to prostatic acid phosphatase (PAP), an antigen expressed in 95% of prostate cancers.
  JCO 24(19): 3089-3094, 2006.(Back)

• The final results from the landmark phase III study reporting that lapatinib (Tykerb®, GlaxoSmithKline) plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer (BC) that had progressed following prior therapy, including trastuzumab, were published in the December 28, 2006 issue of the NEJM. A total of 392 pts were enrolled; 96% had metastatic disease, 97% had prior anthracycline and taxane Rx, 97% had received trastuzumab. Primary endpoint was TTP. Interim analysis of TTP met specified criteria for early reporting due to superiority in the combination arm. Results: TTP with HR 0.49, p=<0.001 favoring the combination arm; median TTP 8.4 months vs 4.4 months favoring lapatinib + capecitabine Rx (p=<0.001). The analysis showed that the addition of lapatinib to capecitabine was associated with a 51% reduction in the risk of disease progression and the trial was stopped. This improvement in outcome was achieved without an increase in serious toxic effects or symptomatic cardiac events.

• According to an announcement last month, the combination of oral capecitabine (Xeloda®, Roche) plus oxaliplatin, known as Xelox, is as effective in delaying disease progression as the chemotherapy combination FOLFOX-4 (infusional 5-FU/leucovorin plus oxaliplatin) in the first-line treatment of patients with advanced colorectal cancer. Analysis of a large (627 pts), international phase III trial (NO16967) comparing the two regimens in pts who had received prior chemotherapy and whose disease had recurred or continued to progress demonstrates that the trial’s primary endpoint of progression-free survival (PFS) has been met. Secondary outcomes included OS, overall response rates, and safety profile. There were no unexpected safety findings in the study. Results from the NO16967 study will be submitted for presentation at future major medical meetings.

• Results of the second planned interim efficacy and safety analysis of the BCIRG 006 phase III study presented at the 2006 San Antonio Breast Cancer Symposium (SABCS) confirm, at a 3-year median follow-up, that trastuzumab (Herceptin®, Genentech) combined with docetaxel (Taxotere®, sanofi-aventis) – based regimens significantly improved disease-free survival (DFS) in women with early-stage HER2-positive breast cancer. The study was designed to maximize efficacy while minimizing toxicity in adjuvant Herceptin (H)-based therapies. Pts: 3,222 enrolled; could be node-positive or node-negative. Primary endpoint was DFS. Randomized to receive the control arm AC-T [4 cycles of doxorubicin (A) and cyclophosphamide (C) followed by 4 cycles of docetaxel (Taxotere = T)] or either of two experimental H and T-based Rx: AC-TH (adds 1 year of H to the AC-T with the H started concurrently with T) or TCH (6 cycles of T and carboplatin (C) with 1 year of H starting with the first cycle). Results: Reduction in the risk of death 41% (p< 0.0041) and 34% (p< 0.017) in the AC-TH and TCH arms, respectively when compared to the non-Herceptin control arm AC-T. The relative reduction in the risk of relapse was 39% (p< 0.001) and 33% (p= 0.0003) for AC-TH and TCH vs control. The interim analysis showed that 92% and 91% of pts were alive at 4 years in the Herceptin/Taxotere-containing arms (AC-TH and TCH) compared to 86% in the AC-T control arm. Note that TCH, the regimen without anthracycline, demonstrated similarly significant improvement in DFS and OS as the AC-TH arm. However, the TCH arm yielded a five-fold decrease in significant cardiotoxicity when compared to the anthracycline/Herceptin-containing arm. Conclusion of presenter: this trial demonstrates an optimal therapeutic index with the use of TCH (not include doxorubicin), thus avoiding the significant cardiac damage related to the sequential use of anthracyclines and trastuzumab. In this interim analysis, 6 cycles of TCH provided similar benefit as AC-TH (8 cycles in total) without increasing cardiotoxicity. There have been no secondary leukemias so far in the TCH arm (4 cases in anthracycline arms). TCH should be considered as an option for women with early stage HER-positive breast cancer, irrespective of nodal status.(Back)

Next issue of OncoFacts™ will be in February 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.

OncoFacts™ is produced by the Network for Medical Communication & Research, LLC (NMCR). NMCR is solely responsible for the content contained in this publication. NMCR assumes no liability for errors that may be in the source material. Neither NMCR nor any of its subsidiaries are affiliated or formally endorsed by any medical society. Copyright 2006 NMCR, LLC. All rights reserved.