Pfizer have recently announced that they will provide the breast cancer drug, palbociclib, free of charge to patients.
Palbociclib is approved for the treatment of patients with locally advanced or metastatic breast cancer, specifically those who have hormone receptor-positive and human epidermal growth factor receptor 2-negative disease. The drug is used in combination with another breast cancer drug, letrozole, which belongs to a different drug class called aromatase inhibitors. The cost of a full course of treatment with palbociclib is approximately £80,000. In a draft guidance, NICE decided against recommending palbociclib due to its high cost in relation to its potential benefits:1
“The committee found that palbociclib stalled the growth of the cancer for an extra 10 months on average. The committee concluded that although it was likely that this would result in some improvement in overall survival, this could not be quantified from clinical trials.”
Pfizer announced that they would provide palbociclib free of charge while the NICE makes a final decision. It is an interesting proposition for pharmaceutical companies to provide drugs to patients on the NHS free of charge. Indeed, the potential benefits from a patient perspective include providing patients with more time before their disease progresses, allowing valuable time to spend time with family and friends.
However, while the addition of palbociclib to an aromatase inhibitor delayed progression of cancer in clinical trials, the drug has so far not been shown to increase the overall survival of patients. In recent years, a number of drugs have received approval based on an increase in progression-free survival without a corresponding increase in overall survival.2 Simply put, while patients will experience a longer time until their disease progresses, ultimately, they will not necessarily live longer than patients not receiving the treatment.
Recently, there has been increasing discussion about the use of progression-free survival as a clinically relevant endpoint in oncology clinical trials and drug approval in the oncology community.2-4 An interesting review by Booth et al. explains that while progression-free survival is measurable, we may be misled into thinking that prolonging it is important. Using progression-free survival compared with overall survival has the advantage of increasing the speed at which clinical trials are completed and, therefore, the speed at which new drugs are evaluated. However, Booth and colleagues believe this trend is worrying, as it “effectively lowers the bar for declaring new drugs to be active when, in fact, [they may] be offering little meaning to our patients.”2 They concluded that it is important that the oncology community and regulatory agencies ensure endpoints used in clinical trials, such as progression-free survival, are of true importance to patients, especially if it they are defining new standards of care.2
It is important to note, that improvements in progression-free survival are correlated with increased overall survival in some clinical trials.3 However, in a study by Adunlin, et al., the authors concluded that this effect may only be relevant for patients with breast cancer who have already received a number of treatments, and not just for patients who have metastatic cancer.3
Therefore, it is important to put the recent ruling of palbociclib by NICE, and other cancer drugs, into perspective. A number of recent news stories and quotes regarding the announcement by Pfizer, have used phrases such as ‘life-saving’ drug and ‘lifeline for thousands,’ which may be misleading to the general public and creating an unfavourable view of the NICE ruling. With the increasing pressure on the NHS, it is important for NICE to ensure robust cost–benefit analyses of new drugs. Therefore, it will be interesting to see the final ruling of NICE on palbociclib.
Reference: 1. NICE News and features. Available at: https://www.nice.org.uk/news/article/breast-cancer-drug-costs-too-high-in-relation-to-benefits-for-routine-nhs-funding Last accessed May 2017; 2. Booth, CM, Eisenhauer EA. J Clin Oncol 2012;30:1030-3; 3. Adunlin G, et al. Breast Cancer Res Treat 2015;154:591-608; 4. Hotte SJ, et al. Curr Oncol 2011;18(Suppl 2):S11-9.