Assessing the validity of progression-free survival as an endpoint in clinical trials

We work on primary liver cancer, that is cancer that starts in the liver – also known as hepatocellular carcinoma (HCC). This is a common cancer (it is predicted by 2025 there will be >1 million cases) that is usually rapidly fatal. Its incidence is rising very fast. (We have published extensively in this area and references are available if required). Sometimes HCC can be cured by surgery but usually it is too advanced for surgery to be effective, by the time it is diagnosed.
In the absence of physical removal of the tumour by surgery or other methods we rely on other approaches such as chemotherapy or immunotherapy. Slow but steady progress is being made in this area. But the progress is impeded because of the cost and complicated nature of the clinical trials that need to be carried out before a new drug can be introduced.
In the field of clinical trials ‘Progression free survival’ (PFS) is a widely used measurement of the effectiveness of a new drug on a particular cancer within a clinical trial. We have major concerns about the validity of PFS:
a) In recent trials, the correlation between PFS and overall survival has been poor suggesting that PFS is not a good way to test a drug’s effectiveness.
b) The calculation of PFS appears to give variable results depending on the time during a trial at which it is assessed.
c) We have noted extreme variation in response to treatment of individual lesions (tumours) within the same organ.
We now seek access to existing clinical trial data in which serial examination of tumour sizes (and certain clinical variables) has been recorded together with reported PFS calculation and overall survival.
This research will establish if PFS is really a good way to measure the efficacy of a new cancer treatment. If this is not the case, then it could have a detrimental effect on patient care through the approval of drugs which may not actually be effective.
We plan to do this through the assessment of a series of simple plots which will show the change in the size of individual tumours in the liver of a patient over time. Therefore, it can be determined whether the behaviour of tumours in response to the same treatment in a patient is consistent over time.