Novartis today expressed great disappointment that the National Institute for Health and Care Excellence (NICE) has issued a final decision not to recommend its innovative advanced breast cancer treatment, Afinitor® (everolimus), to be available to patients on the NHS. Everolimus will continue to be available to patients in England only via the Cancer Drugs Fund (CDF), however, there is uncertainty around access for future patients as the fund may come to an end in 2014 and there is no clear direction as to how treatments will be funded after this.
Everolimus is the first new licensed therapeutic approach in fifteen years offering substantial impact on hormone responsive advanced breast cancer which affects over 30,000 women in the UK.[2, 3] Despite NICE describing everolimus as “a step change in treatment”, its final appraisal determination (FAD) recommends patients should not have access to the therapy via the NHS, marking the sixth treatment that NICE has turned down for patients with advanced breast cancer since 2011.[4-9]
Novartis is extremely disappointed with today’s announcement given the magnitude of clinical benefit that everolimus can offer patients with advanced breast cancer who have limited treatment options available. This is another blow for patients, clinicians and the breast cancer community who have heralded everolimus as a breakthrough treatment representing cutting-edge clinical innovation, which has the potential to change the current treatment pathway. Novartis does not believe that the methodology used to quantify the level of clinical effectiveness, and therefore cost effectiveness, is reasonable. Unless an avenue is found to secure continued access to drugs via the CDF beyond 2014, NICE’s interpretation will risk denying patients access to an effective and much needed therapy within less than a year.
Everolimus is approved for use in postmenopausal women with oestrogen receptor-positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer, in combination with exemestane, that has recurred or progressed following treatment with a non-steroidal aromatase inhibitor. The most common form of advanced breast cancer is the oestrogen receptor-positive type which accounts for approximately 75% of all breast cancers.
Professor Stephen Johnston, Professor of Breast Cancer Medicine at The Royal Marsden NHS Foundation Trust, said, “Everolimus represents a significant advance in the treatment of hormone receptor positive advanced breast cancer and it is disappointing that NICE will not be recommending its routine use on the NHS. For the first time we have a new treatment option which is proven to enhance sensitivity to hormone therapy, ultimately delaying the need for chemotherapy in this setting which is an important benefit for many patients. It is frustrating that because of this decision, a drug with this magnitude of clinical benefit will now not be available to all patients who could benefit.”
A comprehensive range of clinical and cost effectiveness evidence, including data from the pivotal Phase III BOLERO-2 (Breast cancer trials of OraL EverROlimus-2) study involving more than 700 patients, was submitted to the NICE Appraisal Committee and found that:
- treatment with everolimus plus exemestane more than doubled median progression-free survival (PFS) to 11.0 months compared to 4.1 months based on an independent central radiology review
- improvements in PFS with everolimus in combination with exemestane were achieved without compromising health-related quality of life
The most common grade 3-4 adverse reactions seen with everolimus treatment (incidence ³2%) were stomatitis, infections, hyperglycaemia, fatigue, weight decrease, pneumonitis and diarrhoea.
Advanced breast cancer encompasses metastatic breast cancer (stage IV) and locally advanced breast cancer (stage III A, B or C). Metastatic breast cancer is the most serious form of the disease and occurs when the cancer has spread to other parts of the body, such as the bones or liver. Locally advanced breast cancer occurs when the cancer has spread to lymph nodes and/or other tissue in the area of the breast, but not to more distant sites in the body.
Breast cancer is the most common form of cancer in women in the UK and accounts for around 31% of all new cancer cases.[2,12] Of these cases around three quarters are hormone receptor positive (HR+). It is estimated that advanced breast cancer affects over 30,000 women across the UK.[2, 3]
1. National Institute for Health and Clinical Excellence. Final appraisal determination – Everolimus in combination with exemestane for treating advanced HER2-negative hormone-receptor-positive breast cancer after endocrine therapy. Issue date June 2013.
2. Cancer Research UK. Breast Cancer Incidence Statistics. Prevalence. . Last accessed on 18 March 2013.
3. National Institute for Health and Clinical Excellence. Advanced breast cancer costing template CG81. Accessed on 18 March 2013.
4. National Institute for Health and Clinical Excellence. Appraisal consultation document – Everolimus in combination with exemestane for treating advanced HER2 negative hormone-receptor-positive breast cancer after endocrine therapy. Issue date: March 2013.
5. National Institute for Health and Clinical Excellence. Bevacizumab in combination with a taxane for the first-line treatment of metastatic breast cancer. Accessed on 18 March 2013.
6. National Institute for Health and Clinical Excellence. Fulvestrant for the treatment of locally advanced or metastatic breast cancer. Accessed on 18 March 2013.
7. National Institute for Health and Clinical Excellence. Eribulin for the treatment of locally advanced or metastatic breast cancer. Accessed on 18 March 2013.
8. National Institute for Health and Clinical Excellence. Lapatinib or trastuzumab in combination with an aromatase inhibitor for the first-line treatment of metastatic hormone-receptor-positive breast cancer that overexpresses HER2. Accessed on 18 March 2013.
9. National Institute for Health and Clinical Excellence. Bevacizumab in combination with capecitabine for the first-line treatment of metastatic breast cancer. Accessed on 18 March 2013.
10.Baselga, J. Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast Cancer. New England Journal of Medicine. February 9, 2012.
11.Afinitor Summary of Product Characteristics.
12.Murray et al. A randomised study of the effects of letrozole and anastrozole on oestrogen receptor positive breast cancers in postmenopausal women. Breast Cancer Res Treat. (2009) 114:495–501.
13.Piccart M et al. Everolimus for Postmenopausal Women with Advanced Breast Cancer: Updated Results of the BOLERO-2 Phase III Trial. Abstract #559. American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL.
14.Beck et al. BOLERO-2: Health-Related Quality-of-Life in Metastatic Breast Cancer Patients Treated with Everolimus and Exemestane. Abstract #539. American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL.
15.Advani, S. H. Targeting mTOR pathway: A New Concept in Cancer Therapy. Indian Journal Medical Pediatric Oncology. Oct-Dec 2010.
16.National Cancer Institute. What You Need to Know About Advanced Breast Cancer. Accessed on 18 March 2013.