NICE Refuses Funding For Advanced Breast Cancer

NICE issued its final appraisal determination advising against NHS funding for Tyverb® (lapatinib), a treatment for an aggressive form of advanced breast cancer (ErbB2-positive).1 Lapatinib (in combination with Xeloda® [capecitebine]) offers a new treatment option for women whose disease has returned despite treatment with standard chemotherapies and Herceptin® (trastuzumab).2 There are very few treatment options available for these women and lapatinib offers a chance of additional time without their disease progressing.3 Lapatinib is the only licensed ErbB2 targeted treatment* for these patients.


GlaxoSmithKline (GSK) will consider appealing the decision. Simon Jose, General Manager, GSK UK commented; "We disagree with the NICE decision and believe Tyverb is a valuable and important treatment for eligible women. In recognition of the cost effectiveness challenges with drugs that treat patients with a short life expectancy, we offered the Tyverb Patient Access Programme to help ensure it was made available on the NHS. It is difficult to comment without the appearance of self interest. However, there is clearly more work to be done by all parties when flexible access programmes from industry and the recent changes by NICE for patients with a short life expectancy still fail to give them access to valuable medicines."


GSK proposed the patient access programme in the UK when NICE indicated early on in its review that it did not consider lapatinib to be cost effective in treating this patient population. In an effort to achieve a positive outcome for patients and greater value to the NHS, GSK bears the cost of lapatinib, for all eligible patients under the scheme, for up to the first 12 weeks of treatment. The NHS would commence payment only for the patients who continue to receive clinical benefit beyond 12 weeks. GSK will continue to honour the patient access programme for NHS trusts in the UK.


During the lapatinib assessment NICE proposed new advice for the assessment of treatments in small patient populations with a short life expectancy.4 Lapatinib is licensed for a particular type of breast cancer that affects around 2000 women a year.1Therefore lapatinib qualified for review under the new advice.


GSK submitted a sub-group analysis that met the overall survival criterion of this new NICE advice. However NICE concluded that whilst the data analysis could be useful in guiding future research, as it stands it would not change their conclusions. NICE's decision reflects the difficulty in demonstrating significant survival benefits in patients at this advanced stage of disease.1 Furthermore, trials are often halted early for ethical reasons to allow patients to cross over to the















active arm because of the effectiveness demonstrated by the medicine under study, as in the case of lapatinib.5


In its final appraisal determination NICE acknowledges that lapatinib is a clinically effective option, noting that lapatinib plus capecitabine demonstrated improved time to progression (TTP) and progression free survival (PFS) - significantly delaying the progression of the cancer and controlling the disease.1


GSK's NICE submission demonstrated that lapatinib, in conjunction with the patient access programme, could actually save the NHS money in patients who would have received trastuzumab (Herceptin®) containing regimens. NICE acknowledged this is the majority (>50%) of eligible patients, however NICE concluded that trastuzumab is not likely to be cost effective in this setting and therefore lapatinib plus capecitabine would not be cost effective.


Safety Information


Lapatinib plus capecitabine is generally well tolerated. The most common adverse events associated with lapatinib plus capecitabine were diarrhoea, rash, nausea, vomiting, fatigue and hand-foot syndrome.2,3 Diarrhoea and rash were more common with the combination whilst the incidence of hand-foot syndrome was similar between the two treatment groups.2 A decrease in left ventricular ejection fraction (LVEF) was reported by 2.5% of patients receiving lapatinib plus capecitabine vs. 1% of patients on capecitabine alone.2 Hepatobiliary events (mainly raised liver enzymes and/or bilirubin levels) have been reported commonly in association with lapatinib plus capecitabine therapy.2 Lapatinib has also been associated with reports of pulmonary toxicity.2



About Tyverb


- Tyverb, in combination with capecitabine, is indicated for the treatment of patients with advanced or metastatic breast cancer whose tumours overexpress ErbB2 (HER2). Patients should have progressive disease following prior therapy which must include anthracyclines and taxanes and therapy with trastuzumab in the metastatic setting.2


- Healthcare professionals should refer to the Tyverb Summary of Characteristics (SPC) for full prescribing information, including warnings and precautions.2


- * Tyverb received a conditional marketing authorisation in Europe, June 2008.2


GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit gsk


Tyverb® is a registered trademark of the GlaxoSmithKline group of companies. Herceptin® and Xeloda® are registered trademarks of F. Hoffmann-La Roche


GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer.


GlaxoSmithKline


View drug information on Herceptin; Xeloda.

Los Angeles Times Examines Association Between Breast Cancer Risk, Obesity

The Los Angeles Times on Monday examined the association between obesity and the risk of developing breast cancer. According to the Times, a high body mass index for women of childbearing age appears to lower the risk of developing breast cancer; however, the risk increases for girls who have a high BMI before puberty or for postmenopausal women who have a high BMI. A study published last week in the Nov. 27 issue of the Archives of Internal Medicine found that the association between fat and a lower risk of developing breast cancer was stronger earlier in a woman's life, the Times reports. The results of the study "square with the current understanding of how breast cancer develops," according to the Times. Studies have found that women who have a lower lifetime exposure to estrogen have a lower risk of developing breast cancer. In premenopausal women, fatty tissue produces low levels of estrogen that "feeds back on the ovaries and dampens their cyclical release of estrogen," thus subtracting from the total amount of estrogen to which they are exposed, the Times reports. Postmenopausal women have low levels of estrogen, "thus, any extra estrogen from fat is contributing to their total load, not subtracting," according to the Times. "It's like taking a little birth control pill," Anne McTiernan, director of the Prevention Center at the Fred Hutchinson Cancer Research Center, said, adding, "Obese and overweight women are not ovulating normally." In addition, obese and overweight premenopausal women are not producing progesterone -- a hormone associated with a higher risk of developing breast cancer -- in the same way that women of regular weight are, McTiernan said. According to the Times, health experts say the association of developing breast cancer and obesity should not prompt premenopausal women to gain weight. Amtul Carmichael, a breast cancer researcher at Russells Hall Hospital in Dudley, England, said, "[O]bese premenopausal women will become obese postmenopausal women," adding, "Obese women are two to three times more likely to die from breast cancer, and that's common to both pre- and postmenopausal women." In addition, treatments such as chemotherapy might be less effective for obese women because chemotherapy is based on weight, but physicians might give obese women slightly lower doses to avoid toxicity, Carmichael said (Beckman, Los Angeles Times, 12/4).

"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.