No survival, QoL gain for many EMA cancer drug approvals
medwireNews: Research published in The BMJshows that around half of the anticancer drugs recently approved by the European Medicines Agency (EMA) come with no clear evidence of an overall survival (OS) or quality of life (QoL) benefit.
“When expensive drugs that lack clinically meaningful benefits are approved and paid for within publicly funded healthcare systems, individual patients can be harmed, important societal resources wasted, and the delivery of equitable and affordable care undermined,” writes the team led by Courtney Davis, from King’s College London in the UK.
Between 2009 and 2013, the EMA granted a marketing authorization to 48 anticancer medications for 68 indications, but only 24 – just over a third – had evidence they provided an OS gain over existing treatments, best supportive care, placebo, or as an add-on therapy, with the magnitude of gain ranging from 1.0 to 5.8 months.
Just seven indications were associated with a QoL benefit, considered for the purpose of the study as a significant improvement in any item or subscale of a validated instrument, and in the majority (n=5) of these cases the QoL gain came without a concomitant OS benefit at the time of marketing authorization.
In the postmarketing period, with a median follow-up of 5.4 years, a further three indications were shown to be associated with an OS gain and five with some improvement in QoL. However, in one case the OS gain observed at the time of marketing authorization was found not to hold up with longer follow-up.
Davis et al summarize that just 35 (51%) indications were associated with a significant improvement in survival (n=26) or QoL (n=9), while for the remaining 33 (49%) indications, “uncertainty remains” regarding whether the drugs extend or improve life.
They also used the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) to evaluate the clinical value of the reported gains, finding that the gain was clinically meaningful for just 11 (48%) of the 23 indications evaluable with the tool.
Commentator Vinay Prasad (Oregon Health and Science University, Portland, USA), who observed similar results in an analysis of US Food and Drug Administration approvals, says that it appears “the regulatory system is broken.”
He believes that “[t]he default path to market for all cancer drugs should include rigorous testing against the best standard of care in randomised trials powered to rule in or rule out a clinically meaningful difference in patient centred outcomes in a representative population,” with the use of uncontrolled trial designs and surrogate endpoints being “the exception not the rule.”
Speaking to the press, Winette van der Graaf, from the Institute of Cancer Research in London, UK, pointed out that “[i]t takes a long time and costs a lot of money to take treatments through phase III trials and demonstrate an overall survival benefit,” which can be an issue in the setting of rare cancers and means that such patients “would find it extremely difficult to gain access to new treatments.”
Nonetheless, she agrees that “there is room for improvement in the design of clinical studies.”
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