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17-10-2017 | Article

Advisory board comment

Author:
Fiona Blackhall MD, PhD

Comment on: No survival, QoL gain for many EMA cancer drug approvals

The findings in this article reinforce the need to consider objective endpoints that translate to clinically meaningful benefits for patients. The ESMO Magnitude of Clinical Benefit Scale (ESMO–MCBS) has been developed with this aim. Further work is needed to demonstrate its utility in new drug approvals and its impact on trial design moving forwards.

One caveat to the authors’ use of overall survival (OS) as the preferred endpoint for drug approvals in the metastatic setting is that treatments are often given in sequence as different lines of therapy. Each different line of therapy is indicated at or soon after the cancer is observed to progress, usually radiologically, on the current therapy. This means that OS for an individual is the sum of the outcomes from several treatments.

When patients enrolled in a randomized phase III trial can crossover to receive the experimental treatment or an agent with a similar mechanism of action either within or off trial, respectively, the progression-free survival rather than OS is a cleaner primary endpoint. As a case in point, the OS results from the PROFILE 1014 trial of crizotinib compared with chemotherapy were recently reported and shown to be similar for both arms but with a median OS in both arms of over 45 months, far exceeding historical data for chemotherapy alone (median OS 1 year).

It is of course a major goal of palliative therapy for metastatic cancer to not just prolong OS but to optimize quality of life. Living longer and living better will be achieved by treatment with drugs that have demonstrated efficacy after undergoing rigorous testing preclinically and then clinically in well-designed trials for the relevant clinical population. It is important for the approval of new drugs to consider the context and history of their development.

Moving forwards the ESMO–MCBS will assist in the interpretation of single studies and this article reinforces the need for critical appraisal of the evidence base to ensure that the next decades of anticancer therapies are providing more good than harm – both clinically and financially.