More from SABCS 2007

Abstract #41: The ATAC trial comparing 5 years of anastrozole (A) vs 5 years of tamoxifen (T) as the initial adjuvant therapy for postmenopausal women with hormone-sensitive early breast cancer (BC) demonstrated that A is significantly more effective than T in preventing recurrences, has fewer serious side effects, and is better tolerated, but it is associated with a higher risk of fractures on treatment. Although previous reports at a median follow-up (F/U) of 33 and 68 months showed these positive findings, little data exist on whether efficacy benefits or side-effects persist after aromatase inhibitor (AI) treatment is completed.

This abstract presents new data comparing A with T at a median
F/U of 100 months. Primary endpoint was disease-free survival (DFS) and secondary endpoints were time to recurrence (TTR), new contralateral BC (CLBC), time to distant recurrence (TTDR), overall survival (OS), and death after recurrence. Results: significant improvements were seen for A compared with T for DFS (HR 0.85; p=0.003), TTR (HR 0.76; p=0.0001), TTDR (HR 0.84; p=0.022), and CLBC (OR of 0.6; p=0.004). Absolute differences for A and T increased over time (TTR 2.8% at 5 years and 4.8% at 9 years) and HRs remained lower on A vs T after therapy completion. Breast cancer deaths were nonsignificantly (ns) fewer with A than T, but there was no difference in OS (HR=0.97). Conclusions: 1) After median F/U of 100 months, the significant advantage for A over T for TTR, CLBC, and DFS has been maintained with TTDR also significantly superior. (2) Deaths after recurrence remain nonsignificantly lower on A than T. (3) After treatment completion, fracture rates on A were not different than T and no new side-effects were seen. (4) These data confirm the long-term superior efficacy and safety of A over T as initial adjuvant therapy for this patient population.

Abstract #48: This late-breaking abstract (LBA) presents the preliminary results of the ATLAS (Adjuvant Tamoxifen, Longer Against Shorter) international randomized trial of 10 vs 5 years of adjuvant tamoxifen among 11,500 women.

In estrogen receptor-positive [ER(+)] early BC, 5 years of tamoxifen substantially reduces the annual recurrence rate throughout the first decade (years 0-9). Despite this, appreciable risks of recurrence remain, and are persistent. Even with 5 years of treatment with tamoxifen, the annual recurrence risks for ER(+) disease are comparably high during years 0-4, years 5-9, and years 10-14 (and perhaps beyond). It is not reliably known how 10 years of adjuvant therapy with tamoxifen compares with the current standard duration of tamoxifen, which is just 5 years.

ATLAS randomized 11,500 patients (59% ER+, 41% ER untested) who had completed approximately 5 years of adjuvant tamoxifen to either continue for another 5 years (to a total of 10 yrs) or stop taking tamoxifen (control). Results: Mean F/U of 4.2 years per patient with annual recurrence rate in each of the 2 therapy groups approximately constant during and after the 5 year trial treatment period (ie, during years 5-9 and 10-14 after first starting therapy with tamoxifen). One thousand five hundred recurrences have occurred, 1300 during years 5-9 but, in these preliminary results, only 200 during years 10-14. Overall, the recurrence rate was significantly lower among those in tamoxifen continuation arm. No heterogeneity was seen in this recurrence rate reduction with respect to ER status, time period (years 5-9 or 10-14), age, or nodal status. There were approximately 700 deaths after recurrence and about 500 deaths before recurrence. Although BC mortality and overall mortality were lower in those continuing on tamoxifen, these differences were not statistically significant. Discussion: This large study shows that continuation of tamoxifen beyond the first 5 years reduces recurrence over the next few years, but further follow-up is needed to assess reliably the longer-term effects on recurrence and the net effects, if any, on mortality.

Final Notice
The 14th NOCR Annual Meeting will be held March 6-8, 2008, in Las Vegas, Nevada. This symposium uses a variety of educational formats for the exchange of information on the diagnosis and management of solid tumors and hematologic malignancies.

Supportive Care
Dates have just been announced for Perspectives in Oncology Symptom Management. State-of-the-art presentations on an array of topics including alternative therapies for oncologic pain, management of psychological conditions, and osteopenia will be provided by experts in the field of supportive care in oncology. The meeting will be held July 11-12, 2008, in Boston, Massachusetts. Registration opens soon.

Chronic Cannabis Smoking and Lung Cancer Risk

Smoking one cannabis (marijuana) “joint” is equivalent to 20 tobacco cigarettes in terms of lung cancer risk, according to results of a study performed by scientists at the Medical Research Institute of New Zealand. Studies in the past have demonstrated that cannabis can cause cancer, but few have established a strong link between cannabis use and lung cancer.

In an article published in the European Respiratory Journal, the researchers state that cannabis smoke contains twice the level of carcinogens, such as polyaromatic hydrocarbons, compared to the smoke of tobacco cigarettes. In addition to the higher carcinogen levels, the method of smoking cannabis further increases the risk of airway damage. Since joints are usually smoked without filters and almost to the very tip, the amount of smoke inhaled is increased. Cannabis smokers inhale more deeply and for a longer period of time, which facilitates the distribution of carcinogens into the airways. Cannabis smokers have 5 times more carbon monoxide in their blood compared to tobacco smokers.

The investigators questioned patients with lung cancer about tobacco smoking, family history, occupation, and cannabis smoking to determine their risk factors. After adjusting for other variables including cigarette smoking, the lung cancer risk rose by 5.7 times for those who smoked more than a joint a day for 10 years or 2 joints a day for 5 years. Based on their initial evaluation of 79 patients from this ongoing study, the researchers conclude that these results clearly show that long-term cannabis smoking increases lung cancer risk and could be responsible for one in 20 lung cancers diagnosed in New Zealand.

Digital Mammography: Who Needs It?

The Digital Mammographic Imaging Screening Trial (DMIST), initiated in 2001, was designed to compare digital mammography with traditional film-based mammography in 49,528 women. Early findings of the trial, published in 2005, suggested that younger women and women with dense breasts would benefit from digital mammograms, but also found that the digital test was no better than film mammography for the overall population of women. Unlike traditional mammograms, digital ones can be stored on a computer and the images can be enhanced and sent electronically. The digital type also uses less radiation than film mammograms, but the digital systems cost about 1.5 to 4 times more than the film systems.

In a more recent study, published in the journal Radiology, researchers performed a new analysis of the DMIST data to determine which women would benefit most from digital mammograms. They studied several subgroups of women including those of different age groups, menopausal status, and dense vs fatty breast tissue. Their results confirm earlier findings that the digital system was better for premenopausal and perimenopausal women under 50 years of age with dense breasts. For women over 65 years of age with fatty breasts, film mammography appeared to work better. For other groups, there was no significant difference between the 2 types of mammography.

Could a Simple Blood Test Predict Colon Cancer Survival?

At the 2008 Gastrointestinal Cancer Symposium late last month, investigators from the Fox Chase Cancer Center in Philadelphia presented information in abstract form (Abstract No. 299) titled: Circulating Tumor Cells (CTC), Progression-Free (PFS) and Overall Survival (OS) in Metastatic Colorectal Cancer (mCRC): A Subgroup Analysis of a Large Multicenter Study. The group recently demonstrated that CTC number at baseline and during therapy is an independent prognostic factor for PFS and OS for patients with mCRC who are beginning a new line of systemic therapy. The current analysis was to evaluate the relationship of pretreatment CTC number with outcome by treatment line (1st, 2nd, 3rd), type, and important clinical characteristics of patients (age, ECOG PS, liver metastases). Four hundred thirty patients with mCRC provided 7.5 mL of blood that was tested for CTC using immunomagnetic separation before starting first-, second-, or third-line therapy and at follow-up visits.

Results: Patients stratified into unfavorable (≥3 CTC per 7.5 mL blood) and favorable (<3 CTC per 7.5 mL blood) prognostic groups based on pre-therapy blood levels. Patients with favorable CTC levels before therapy had OS more than twice as long (19 months) as those with unfavorable CTC levels (9 months). Median PFS for patients with CTC levels that were “high” (unfavorable) progressed much sooner than those with “low” (favorable) CTC levels at 5 months vs 8 months, respectively. Conclusions (authors): CTC levels before treatment are an independent predictor of PFS and OS in patients with mCRC regardless of line of therapy, type of therapy, or clinical characteristics. Authors comments: 1) These results held up regardless of a patient’s age, type of therapy, extent of disease, or overall health. 2) A high CTC level doesn’t mean that a patient won’t respond to therapy, just that the person might not do as well as someone with a low CTC level. If people with high CTC levels begin therapy and their CTC levels drop substantially within several weeks, their risk of relapse or dying decrease also.

Industry News

FDA Actions

On January 30, 2008, the FDA granted priority review status to Millennium Pharmaceuticals Inc.’s bortezomib (Velcade®) for use in the treatment of patients with newly diagnosed multiple myeloma. The supplemental New Drug Application (sNDA) submitted to the FDA for this indication included data from the phase III VISTA trial comparing a bortezomib-based regimen VcMP (bortezomib, melphalan, prednisone) to a traditional standard of care, melphalan-prednisone (MP), alone. VcMP achieved statistically significant improvement of all efficacy endpoints (CR, TTP, PFS, and OS) when compared to MP alone in 682 patients with newly diagnosed myeloma. The company anticipates a potential approval decision from the FDA by June 2008.

On January 31, 2008, the FDA accepted the supplemental Biologics License Application (sBLA) for Schering-Plough Corporation’s peginterferon alfa-2b (Pegintron™) for the adjuvant treatment of patients with stage III malignant melanoma. The FDA has also granted priority review status for the sBLA which expedites the review process with a goal of taking action within 6 months. The application will be discussed by the FDA Oncology Drugs Advisory Committee (ODAC) on March 12, 2008.

At the March 12, 2008, ODAC meeting, the committee will also review and discuss the BLA for Amgen Inc.’s romiplostim (Nplate, formerly AMG 531), an investigational thrombopoiesis-stimulating agent, for use as treatment of thrombocytopenia in adults with chronic idiopathic (immune) thrombocytopenia (ITP). The BLA was submitted to the FDA in late October 2007 and was granted priority review status with an estimated FDA action date in April 2008. The proposed indication is for treatment of chronic adult ITP patients who are nonsplenectomized and have had an inadequate response to or are intolerant of corticosteroids and/or immunoglobulins; or patients who are splenectomized and have an inadequate response to splenectomy.

The next issue of OncoFacts will be in March 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