A new study in the journal BMJ concludes that most oncology drugs approved by the European Medicines Agency between 2009 and 2013 failed to display a benefit on survival or quality of life, even at 3.3 years following market entry.
A new study in the journal BMJ concluded that most oncology drugs approved by the European Medicines Agency (EMA) between 2009 and 2013 failed to display a benefit on survival or quality of life (QOL), even at 3.3 years following market entry.
Surrogate endpoints have become commonplace in cancer clinical trials, and they are developed with the objective of being able to predict long-term survival outcomes. These endpoints include progression-free survival, objective response rate, disease-free survival, and tumor shrinkage, among others. While some of these markers are a better indicator of a drug’s biological activity, their impact on survival and a patient’s QOL remains a point of debate.
In the present study, researchers affiliated with several institutions across the United Kingdom—including King’s College London and the London School of Economics and Political Science—assessed publicly available regulatory and scientific reports on cancer approvals by the EMA between 2009 and 2013. The primary outcomes of the study included availability and magnitude of benefit on overall survival and QOL, both when approved and following market entry. Clinical value of treatment was assessed using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS).
The authors found that of the 48 cancer drugs that were approved for 68 indications, 8 drugs (12%) were approved based on a single-arm study, with significant prolongation of survival in 24 indications (35%). Overall survival benefit ranged between 1.0 to 5.8 months (median, 2.7 months). With respect to QOL benefit, only 7 of 68 (10%) indications showed an improved QOL at the time of marketing approval.
Evaluation of 44 indications that had no survival gains when they were authorized for marketing showed that 3 (7%) indications improved survival during the postmarketing period and 5 (11%) had a beneficial effect on QOL. Overall, at a median follow up of 5.4 years (range, 3.3 years to 8.1 years), only 35 drugs (51%) had shown a significant improvement in survival or QOL, while 33 (49%) remained uncertain. The ESMO-MCBS tool found that less than half the indications—11 of 23 (48%)—that were associated with a survival benefit were clinically meaningful.
Highlighting the negative impact of such a situation on patients and on overall public health, the authors concluded, “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.”
Davis C, Naci H, Gurpinar E, Poplavska E, Pinto A, Aggarwal A. Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13. BMJ. 2017;359:j4530. doi: 10.1136/bmj.j4530.