Revisiting NICE's approval of 'breakthrough' drugs palbociclib and ribociclib
Claims of cancer drugs’ survival benefits must be accurate. To avoid fashion and fads, we must carefully examine the clinical and economic implications of newly approved cancer drugs before we seat them on the ‘breakthrough’ throne.
In November 2017, the National Institute for Health and Care Excellence (NICE) approved palbociclib and ribociclib (for post-menopausal patients), for medical use in combination with an aromatase inhibitor, in women in the UK with hormone (oestrogen or progesterone) receptor-positive / human epidermal growth factor receptor 2 (HER2)-negative, locally advanced breast cancer.
Examining the clinical implications
1. An average of 10-month improvement in progression-free survival (PFS) is noted.
2. The two drugs ‘might be’ beneficial and to ‘only’ 8,000 British women per year.
3. It is argued that the drugs would delay the need for chemotherapy and avoid the therapy’s unpleasant adverse effects (AEs), but palbociclib and ribociclib are not free from AEs.
4. Several trials showed AEs of grade 3/4 neutropenia with palbociclib in combination treatments. This may give lower or non-adherence. The NHS loses £500m a year to non-adherence.
5. During PALOMA trials with palbociclib, many patients underwent dose reduction and discontinuation. Medical professionals recommend dose reduction to ameliorate AEs. Research shows dose reduction and interruption with palbociclib negatively affects patient outcomes in regard to PFS, overall survival and onset to subsequent therapy. Dose reduction and discontinuation also lead to medication wastage because prior prescription doses cannot be retained for later or split. This would affect pharmacy costs, constrain the NHS budget, and allocate funds away from critical issues in healthcare, which was shown to increase the mortality gap in UK.
6. At the European Society for Medical Oncology Congress 2017, I attended the MONARCH III trial results session, which detailed a new member of CDK4/6 inhibitors’ second generation. Abemaciclib is more selective than the palbociclib and ribociclib, and the AE profile is expected to be better. Palbociclib and ribociclib are outdated within their generation.
Assessing the economic implications
1. The less clinically established drug, ribociclib, is approved for a third of the price per capsule compared with that of palbociclib, despite the similar mechanism of action and clinical outcomes.
2. The approval alleviates pressure from the Cancer Drugs Fund, and drives greater value from taxpayers’ increasing investment in cancer therapies; however, confidentiality arouses curiosity.
The drugs may seem beneficial, but ‘breakthrough’ is a loaded word reserved for ‘sustainable’ cancer drugs. Research has shown that drugs not approved by the US Food and Drug Administration were heralded as ‘breakthrough’ in the press 50% of the time. This leads to false and bias connotations, especially by patients.
NICE’s approval of palbociclib and ribociclib is a step in the right direction to possibly prolonging the lives of many women. But the ‘breakthrough’ description must be revisited and put into clinical, social and economic context.
University of Texas MD Anderson Cancer Center
Citation: Clinical Pharmacist DOI: 10.1211/CP.2017.20204074
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