More from ASH 2007

Abstract 187: Lenalidomide (Revlimid®, Rev) and Bortezomib (Velcade®, Vel) plus Dexamethasone (Dex) as Front-Line Therapy for Patients with Newly-Diagnosed Multiple Myeloma (MM): Preliminary Results of a Phase I/II Study. Goals were to determine maximum tolerated dose (MTD) of Rev/Vel/Dex, and to assess safety and efficacy. Multiple doses of the 3 drugs were used in dose-escalation fashion, and based on safety data the starting dose (Rev 25 mg, Vel 1.3 mg/m2, Dex 20 mg in all cycles) was given for up to eight 21-day cycles. Patients with G>2 peripheral neuropathy (PNY) were excluded; those with serum creatinine up to 2.5 mg/dL were accepted. Results: 53 patients enrolled (median age 56 years, 55% men, 84% IgG), median of 6 cycles of therapy. Toxicities were manageable with only one G4 toxicity (Tpenia), 2 deep vein thrombosis (DVT), reversed with LMWH, and no G≥3 PNY reported. Response rate across all dose cohorts (clinical response [CR]/near CR + very good partial response [VGPR]+partial response [PR]) is 98% including 52% CR and 29% near clinical response (nCR)+VGPR. Conclusions of authors: 1) Rev/Vel/Dex very active [98% relative response (RR) overall] and well tolerated in newly-diagnosed patients with MM. 2) Maximum planned dose reached at Rev 25 mg, Vel 1.3 mg/m2, and Dex 20 mg. 3) No significant G3-4 PNY seen.

Register today for The 14th NOCR Annual Meeting March 6-8, 2008 in Las Vegas, Nevada! This symposium features a world-class faculty and a variety of educational formats for the exchange of information on the diagnosis and management of solid tumors and hematologic malignancies. Register online at www.asoncology.com.

Only a few dates remain for Hematology and Breast Cancer Highlights. Local and internationally renowned experts will summarize and interpret the most clinically significant data released from recent meetings. Register online at www.asoncology.com.

Hematology Highlights: Highlights from the 49th Annual Hematology Meeting
February 2, 2008 New York, NY – Sold Out
February 16, 2008 Los Angeles, CA

Breast Cancer Highlights: Highlights from the 30th Annual San Antonio Breast Cancer Symposium
February 9th, 2008 New York, NY
February 16th, 2008 Chicago, IL

Industry News

The New Gold Standard for CT Scans?

Computed tomography (CT) scan radiation has become a medical issue. The December 2007 Quick Poll question and discussion of this newsletter dealt with this issue. As you may recall, an article in the November 29, 2007 New England Journal of Medicine (NEJM) titled: “Computed Tomography – An Increased Source of Radiation Exposure” asserted that the radiation from CT may cause up to 2% of all cancers in the US. The concern raised in this article stems from study results that demonstrate a several-fold higher amount of radiation is delivered by CT than any other radiology examination, plus the statement that 1.5% to 2% of all cancers theoretically may be caused by CT. On November 30, 2007, an ASCO Member Alert was sent via email to active members of ASCO regarding this situation.

On December 18, 2007, a Washington Post article reported that Philips Medical Systems had developed a new device, the Brilliance iCT scanner, that uses 80% less radiation than conventional CT scanners. It is 22% faster and has 4 times the resolution of other scanners. The new device can take 256 image slices of organs, such as the heart, or brain, compared to the usual 16 or 64 slices. A full-body scan takes less than a minute and images of the heart can be taken in just two heartbeats versus the standard five. This is close to essentially “freezing” the motion of the heart, which is important when trying to examine a child or a trauma patient who cannot hold his breath or stay still. This device has been in use since November 2007 at the MetroHealth Medical Center in Cleveland.

NCCN Updates Breast Cancer Guidelines:

The National Comprehensive Cancer Network (NCCN) has announced several new updates to the NCCN Clinical Practice Guidelines in Oncology™ Breast Cancer.

1. A new section focusing on the treatment of patients with inflammatory breast cancer (IBC) has been added. Recommendations from the NCCN Guideline Panel for treatment of IBC (without evidence of metastases) involve a combined modality approach, including preoperative chemotherapy with an anthracycline with or without a taxane followed by total mastectomy and radiation therapy for patients responding to preoperative chemotherapy.
2. The option of using a gene-based assay of tumor tissue (Oncotype DX®, Genomic Health) to help guide chemotherapy treatment decisions is now included within the systemic adjuvant treatment decision pathway for patients with hormone receptor-positive, HER2-negative tumors that are 0.6 cm to 1.0 cm and moderate/poorly differentiated or with unfavorable features, or greater than 1 cm.
3. Bevacizumab (Avastin®, Genentech) continues to be a recommended therapy in combination with paclitaxel for the treatment of recurrent or metastatic breast cancer.
4. The NCCN Breast Cancer Guidelines V.2.2008 now includes new sections covering principles of breast reconstruction following mastectomy and principles of radiation therapy.

For more information, visit www.nccn.org.

Physicians in the Baltimore, Rochester (MN), and San Francisco areas are invited to attend a complimentary dinner meeting on Chronic Myeloid Leukemia: A Practical Approach to Current Management. These short educational meetings provide valuable practice updates in a relaxed, collegial setting. Details are available at www.cmlupdates.com.

If you are looking to travel, upcoming conferences on hematologic malignancies (Paris, France), febrile neutropenia (Brussels, Belgium), lung cancer (Torino, Italy) CNS Malignancies (Berlin, Germany) and gastrointestinal cancer (Barcelona, Spain) offer attendees the opportunity for international travel and comprehensive educational updates. Details are available at www.imedex.com.

Looking ahead, be sure to mark your calendars for Perspectives in Colorectal Cancer, which will be held September 19-20 in Miami, Florida and Lymphoma & Myeloma 2008, scheduled for October 16-18 in New York City. Details coming soon!

This section will be dedicated to the 2007 San Antonio Breast Cancer Symposium (SABCS) with brief capsule summaries of important abstracts (Abs.) presented at the meeting. These abstracts are available online at (www.sabcs.org) the official Website of the SABCS. Expert thought leader discussions and interviews by James Epstein, MD are available at www.asoncology.com via our “Best of the Day” activity.

Abstract 10: Prognostic and Predictive Value of the 21-Gene Recurrence Score Assay (RS) in Postmenopausal (postMP), Node-Positive, ER(+) Breast Cancer (S8814, INT0100).

The 21-gene Recurrence Score assay (RS) is prognostic for women with node(-), ER(+) breast cancer (BC) treated with tamoxifen (T) alone and a high RS predicts a large, additional chemotherapy benefit. However, there are no data in a node(+) population with a T-alone control. The 2 primary objectives of this analysis were to determine if the RS: (1) provides prognostic data for disease-free survival (DFS) in the T-alone control arm and (2) predicts a group of patients (pts) that does not benefit from chemotherapy followed by T, despite positive nodes.

The phase III trial S8814 for postMP women with node(+), ER(+) breast cancer showed that cytoxan, doxorubicin, and 5-fluorouracil (CAF) chemotherapy added DFS and overall survival (OS) benefit to T-alone at 10 years, especially if T followed (CAF-T). Optional specimen banking from 45% of S8814 patients yielded tumor tissue blocks for analysis of the 21 genes for the RS. Analyses for DFS and OS were conducted by the Southwest Oncology Group (SWOG) using the T-alone and CAF-T arms of S8814 (367 patients).

Results: RS risk distribution was 40% low risk (<18), 28% intermediate risk (18-30), and 32% high risk (≥31). The RS was prognostic for DFS in the T-alone arm (p=0.006), with similar effects in the 1-3 and 4+ node subsets and for OS. There was no apparent DFS or OS benefit to CAF-T vs T-alone in the low RS group (10-year DFS 64% CAF-T vs 60% for T, p=0.97), whereas there was a large CAF benefit in the high RS subset (10-year DFS 55% for CAF-T vs 43% for T-alone, p=0.03). There was no statistical benefit in patients with intermediate risk. Continuous RS was prognostic in T-alone in the first 5 years (p<0.001), but not subsequently (p=0.80). For prediction of CAF benefit, the RS by treatment interaction was significant in the first 5 years for DFS (p=0.029), but not after 5 years (p=0.58), with nodal status strongly prognostic for both time periods. Results were similar for OS. Although the effects of RS on hazard rates were concentrated during the first 5 years, cumulative effects on DFS and OS were still observed at 10 years.

Conclusions: (1) The RS is prognostic for T-treated patients with positive nodes. (2) It is predictive of added CAF benefit in those patients whose tumors have a high RS. (3) A low RS may define a group of women with positive nodes who do not appear to benefit from anthracycline-based adjuvant chemotherapy.

Abstract 12: Extended Follow-up and Analysis by Age of the US Oncology Adjuvant Trial 9735: Docetaxel/Cyclophosphamide Is Associated with an Overall Survival Benefit Compared to Doxorubicin/Cyclophosphamide and Is Well-Tolerated in Women 65 or Older.

At SABCS 2005, the 5-year results were reported of a randomized trial of 4 cycles of docetaxel/cyclophosphamide (TC) compared to 4 cycles of doxorubicin/cyclophosphamide (AC) in women with node(-) (approx 50%) and node(+) early BC. A significant improvement in DFS, but not OS was observed. Older women are not commonly enrolled on adjuvant chemotherapy (CT) trials. It has been reported that only 8% of women on CALGB trials were ≥ 65 years of age. In the AC/TC trial, 16% (160 patients) were ≥ 65 years of age. With 2 more years of F/U, the investigators now report on OS as well as the effect of Rx by age (using 65 as the cutoff) on outcome and toxicity.

One thousand sixteen patients with stage I-III operable invasive BC with complete surgical excision of primary tumor randomized to 4 cycles of either AC (n=510) or TC (n=506) q3 weeks as adjuvant chemotherapy. Results: Median age in patients aged < 65 years was 50 years and for those aged ≥ 65 years was 72 years. Median F/U 6.9 years and the difference in OS between TC and AC is significant. Overall DFS: TC 85% vs AC 79% (p=0.018, HR is 0.69); DFS<65: TC 88% vs AC 82% (HR=0.64) and DFS ≥65 is TC 82% vs AC 75% (HR=0.69). Overall survival for TC 88% vs AC 84% (p=0.045, HR=0.73). In the TC patients, 75 DFS events (15%) and 57 deaths (11%); in the AC patients 108 DFS events (21%) and 83 deaths (16%). Younger patients in both the TC and AC groups had less febrile neutropenia (4.4% and 2.3%, respectively) compared to older patients (7.7% and 3.7%, not significant). Toxicity by treatment was similar in both age groups to the groups as a whole.

Conclusions: With longer follow-up, TC was associated with improved DFS as well as OS, compared to standard AC. TC should now be a standard non-anthracycline combination for early BC. In addition, TC was well-tolerated in older women without excessive toxicity compared to their younger counterparts, and may be preferable due to its lack of cardiotoxicity.

The next issue of OncoFacts will be in February 2008 and then monthly throughout the year.

OncoFacts Editor:

Jim Jones, MD

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

OncoFacts is produced by the American School of Oncology. The American School of Oncology is a brand and assumed name used by Imedex^®, LLC. Imedex is solely responsible for this program’s content. Although Imedex attempts to ensure that the information in our programs is accurate and timely, matters and opinions discussed and/or presented with respect to clinical matters are those of the discussion participants only, and not necessarily those of Imedex. Moreover, although Imedex attempts to identify and integrate the most qualified medical professionals and key thought leaders in our programs, TO THE FULLEST EXTENT PERMITTED BY LAW, IMEDEX EXPRESSLY DISCLAIM ALL WARRANTIES, EITHER EXPRESS OR IMPLIED, STATUTORY OR OTHERWISE, INCLUDING BUT NOT LIMITED TO THE IMPLIED WARRANTIES OF MERCHANTABILITY, NON-INFRINGEMENT OF THIRD PARTIES’ RIGHTS, AND FITNESS FOR A PARTICULAR PURPOSE, WITH RESPECT TO THE CONTENT PRESENTED. IMEDEX FURTHER MAKES NO REPRESENTATIONS OR WARRANTIES ABOUT THE ACCURACY, RELIABILITY, COMPLETENESS OR TIMELINESS OF THE CONTENT OR ANY MATERIAL PRESENTED.

In addition, the material presented and related discussions are not intended to be medical advice, and the presentation or discussion of such material is not intended to create and does not establish a physician-patient relationship. Medical advice of any nature should be sought from an individual’s own physician.

Neither Imedex nor any of its subsidiaries or affiliates is affiliated with or formally endorsed by a medical society.

© 2008 Imedex, LLC. All rights reserved.

If you would like to be removed from this list, please click here