For the December issue of OncoFacts, I will be updating you regarding 2 significant changes from organizations regarding routine screening recommendations for breast cancer and cervical cancer. However, prior to that, I would like to highlight a CDC collaborative report that focuses on prevention recommendations and usage for adults aged 50 to 64 in the United States.

US Preventive Service Task Force (USPSTF) Published New Breast Cancer Screening Guidelines

1. The Task Force recommends against routine screening for women ages 40 to 49. Whether to start screening before age 50 should be an individual choice.
2. The Task Force recommends screening every 2 years for women between ages 50 and 74.
3. The Task Force cannot make any recommendations on whether women ages 75 and over should be screened because there is not enough evidence upon which they can base a recommendation.
4. There is not enough evidence to make a recommendation about the value of clinical breast examination (a careful breast exam done periodically by a trained medical professional) for women 40 years of age or older
5. There is no evidence that teaching women how to do breast self examination makes an difference, so they recommend against teaching women how to do it
6. There is not enough evidence to say anything about the value of digital mammography and magnetic resonance imaging (MRI) screening in women at average risk of breast cancer

The American Cancer Society and multiple other organizations responded swiftly to these new recommendations by disagreeing with their conclusions and suggesting that the gains that we have made in reducing breast cancer mortality in this country will now begin to reverse.

What do we know about mortality from breast cancer currently? We know that deaths from breast cancer have declined 2.3% per year for all women, and 3.3% per year for women aged 40 to 49 beginning in the year 1990. Prior to 1990, the mortality rate was stable for about 6 decades. Some of this improvement in mortality is as a result of new and improved systemic therapy for breast cancer, and some is as a result of routine mammographic screening.

The USPSTF states that mammography screening at any age is a tradeoff of a continuum of benefits and harms, and that the age at which this tradeoff becomes acceptable to individuals and to society is not clearly resolved by available evidence. The USPSTF says there is a small net benefit for women aged 40 to 49 to get routine screening, so the decision to start screening mammography before age 50 should be individualized and take into account patient context including her values regarding specific benefits and harms.

The USPSTF looked at a meta-analysis from 8 trials that included screening mammography in women aged 39 to 49. When combining results, the pooled relative risk for women invited to be screened versus women getting standard care was 0.85, which indicates a 15% reduction in mortality from breast cancer. However, since breast cancer is less common for women in their 40s compared to those in their 50s or 60s, it would take 1904 women being invited to screening annually to prevent 1 breast cancer death. For women aged 50 to 59, there was a similar 15% relative reduction in mortality from breast cancer for those invited to be screened, but that it would take 1339 women being screened to save 1 life. For women aged 60 to 69, there was a 32% reduction in mortality with 377 women needing to be invited to screening for 1 life to be saved.

The American Cancer Society recommends regular mammography screening based primarily on the published evidence from international prospective randomized clinical trials. These trials are regularly re-analyzed; especially those that continue to follow the patients in the studies. When these studies are combined, mammography reduced breast cancer mortality by at least 15% to 20% for women ages 40 to 49 and 50 and older, while some individual studies demonstrated mortality reductions of 30% or greater for women in their 40s and women ages 50 and above. While the USPSTF principally considers the results when all trials are combined, the American Cancer Society looked more carefully at individual trials and large population studies that have been done more recently.

It should be noted that many of these clinical trials began prior to the 1990s. The mammography technology used at that time was not as advanced as it is today, nor was there an appreciation that breast cancer grows faster in younger women, and thus they will not likely benefit when the screening interval is every 24 months or longer. Experts believe that current mammography technology offers an even greater benefit because of well-documented improvements in imaging, interpretation of findings, and mandated quality and safety standards – all with reduced radiation doses.

For further information regarding this controversy, the USPSTF articles are found in the November 17, 2009 Annals of Internal Medicine. The response from the American Cancer Society can be found on their website: www.cancer.org.

Reference:
US Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;151(10):716-26, W-236.

Clinical Practice Guideline Update for Stage IV Non-Small Cell Lung Cancer: New American Society of Clinical Oncology^® (ASCO) Guidelines.

On November 16, 2009, ASCO published updated recommendations for the treatment of patients with stage IV non-small cell lung cancer (NSCLC). They reviewed 162 publications that met inclusion criteria for consideration. The following recommendations were obtained from the ASCO website:

Recommendations: The recommendations were base on treatment strategies to improve overall survival. Treatments that only improved progression-free survival promoted scrutiny of quality of life and toxicity. A platinum-based 2-drug combination of cytotoxic drugs was recommended for the first-line treatment of patients with performance status 0 or 1. For patients with contraindications for platinum therapy, non-platinum cytotoxic doublets were considered acceptable. A single cytotoxic drug is sufficient for patients with a performance status 2. In patients who do not respond to treatment, stopping first-line cytotoxic chemotherapy at disease progression or after 4 cycles is recommended. Even in patients who respond to therapy, the recommendation is to stop 2-drug cytotoxic chemotherapy at 6 cycles. For patients with known EGFR mutation, the first-line use of gefitinib may be recommended; however, for patients with negative or unknown EGFR mutation status, cytotoxic chemotherapy is preferred. Treatment with bevacizumab is recommended with carboplatin-paclitaxel, except for patients with certain clinical characteristics. For patients with EGFR-positive tumors by immunohistochemistry, cetuximab is recommended with cisplatin-vinorelbine. For second-line therapy, docetaxel, erlotinib, gefitinib, or pemetrexed are recommended. In third-line therapy, for patients who have not received prior erlotinib or gefitinib, erlotinib is recommended. Data are insufficient to recommend the routine third-line use of cytotoxic drugs, and data are insufficient to recommend routine use of molecular markers to select chemotherapy.

Reference:
Azzoli CG, Baker S, Temin S, et al. American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage IV non-small cell lung cancer. American Society of Clinical Oncology (ASCO) website. 2009. Available from: http://www.asco.org/ASCO/Downloads/Cancer%20Policy%20and%20
Clinical%20Affairs/Clinical%20Affairs%20(derivative%20products)
/NSCLC/NSCLC%20Unabridged%2011.23.09.pdf. Accessed December 20, 2009

The US Food and Drug Administration (FDA) routinely publishes online What’s New from the Office of Oncology Drug Products

The following information is for your perusal.

2009

• November 6, 2009 – Romidepsin for injection for the treatment of cutaneous T-cell lymphoma (CTCL) was approved by the FDA for use in patients who have receive at least 1 prior systemic therapy.
• October 26, 2009 – Ofatumumab was approved by the FDA for the treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab
• October 19, 2009 – Pazopanib tablets were approved by the FDA for the treatment of patients with advanced renal cell carcinoma
• September 24, 2009 – Pralatrexate injection was granted accelerated approval by the FDA for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL)
• July 31, 2009 – Bevacizumab use in combination with interferon alpha was approved by the FDA for the treatment of patients with metastatic renal cell carcinoma
• July 17, 2009 – The FDA implemented Class Labeling Changes of anti-EGFR monoclonal antibodies, cetuximab and panitumumab. Changes regarding KRAS mutations were made to the product labels of cetuximab and panitumumab
• July 2, 2009 – Pemetrexed was approved by the FDA for maintenance treatment of locally advanced or metastatic nonsquamous NSCLC patients with no disease progression after 4 cycles of platinum-based first-line chemotherapy.
• June 30, 2009 – Ferumoxytol was approved by the FDA for the treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD). Ferumoxytol is an iron-containing product for intravenous (IV) administration
• May 5, 2009 – Bevacizumab injection received accelerated approval by the FDA as a single agent for patients with glioblastoma with progressive disease following prior therapy.
• March 31, 2009 – Everolimus tablets received FDA approval for the treatment of patients with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib

During the morning session on December 16, 2009, the committee will discuss supplemental new drug application (sNDA) 021-743/S-016 regarding erlotinib tablets. The proposed indication for this product is first-line maintenance, monotherapy (first-choice, single drug) treatment in patients with NSCLC that is either locally advanced (has spread regionally within the lung and/or within the chest lymph nodes) or metastatic (has spread beyond the lung) and who have not progressed (including those patients with stable disease) on first-line treatment with platinum-based chemotherapy (a regimen including a platinum drug [cisplatin or carboplatin] plus another chemotherapy drug).

During the afternoon session, the committee will discuss sNDA 022-059/S-007 for lapatinib tablets. The proposed indication for this product is in combination with an aromatase inhibitor for the treatment of hormone sensitive advanced or metastatic breast cancer.

Reference:
FDA.gov. What’s new from the office of oncology drug products. US Food and Drug Administration website. 2009. Available from: http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm093885.htm. Accessed December 15, 2009.

FDA.gov. December 16, 2009: Oncologic drugs advisory committee meeting announcement. US Food and Drug Administration website. 2009. Available from: http://www.fda.gov/AdvisoryCommittees/Calendar/ucm191240.htm. Accessed December 15, 2009.

I hope that the 2009 issues of OncoFacts have been enlightening, and I hope the discussion of these new screening recommendations will provide for you some food for thought. I look forward to presenting the 2010 issues of OncoFacts.

OncoFacts™ Editor:

Christy Russell, MD

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