Articles

“Is progression-free survival time predictive of overall survival? Analysis of studies of targeted therapies in oncology”

 

 

 

 

“Is progression-free survival time predictive of overall survival? 

Analysis of studies of targeted therapies in oncology”

by G. Delépine, N. Delépine, S. Alkhallaf

 

presented in Bobigny congress  2017

 

 

Introduction

The duration of progression-free survival (PFS) is the first criterion of judgment of more than 90% of the trials of the current innovative therapies at the time of the MA application. This PFS is supposed to be predictive of overall survival and therefore of future usefulness for patients. This work aims to verify it as well as its predictive value of clinical utility for patients.

 

Method

A computerized search with key words Avastin, Herceptin, Erbitux, erlotinib, sorafenib, gefitinib, crizotinib, afatinib, temsirolimus, pazopanib, sunitinib, axitinib, in bronchopulmonary squamous cell carcinoma, kidney, colon, breast and ENT was realized. 110 trials were then examined to select those where SPP and long-term outcomes were published detailing overall survival and toxicity (51 studies). The gains in progression-free survival durations reported in the pivotal study were then compared to those of overall survival.

 

Results

The progression-free survival gains reported by the pivotal studies of targeted therapies are not correlated with a possible overall survival benefit or with a potential gain in quality of life. This result confirms many macroanalyses including those of Petrelli and the Cochrane Institute (for TKI and lung cancers), and the Cochrane Institute (for Avastin and breast cancer).

 

Conclusions

In trials of targeted therapies in oncology, the duration of progression-free survival does not prejudge either the overall survival time or a favourable benefit / risk balance. Favouring this criterion to award the AMM results in exposing patients to significant risks and most often without any real benefit. It should therefore no longer be accepted as the main crite

 

“Are the results of pivotal studies in oncology reliable?” in Overconsumption, overtreatment Bobigny congress 2017

 

 

colloque bobigny 2017 resultats-pivots

Colloque_2017_bobigny-poster-SSP_G_DELEPINE

two presentations in french  with curves of the results

 

“Are the results of pivotal studies in oncology reliable?”

by G. Delépine, N. Delépine, S. Alkhallaf

 

 

 

Introduction

Over the last fifteen years, the authorization to put innovative therapies on the market has been granted after one or sometimes two short placebo-controlled studies on a small number of patients. To see if these pivotal studies are reliable, we compared their initial results with the latest published results.

 

Material and methods

A computerized search with key words Avastin, herceptin, erbitux, erlotinib, sorafenib, gefitinib, crizotinib, afatinib, temsirolimus, pazopanib, sunitinib, axitinib, in bronchopulmonary squamous cell carcinoma, kidney, colon, breast and ENT cancers has been realized to find 42 pivotal studies. We then looked for those with distant results specifying the duration of progression-free survival, Overall survival and toxicity were published (32) and compared the results of the pivotal studies with those of the last trials on these three criteria.

 

Results

Less than 30% of the results presented to the regulatory agencies during marketing authorization applications are fully confirmed by subsequent trials. 20% of them are confirmed for 1 or 2 criteria. The discrepancies observed between initial and late results are always in the direction of greater efficacy or less toxicity of the new drug in the pivotal study.

 

Conclusions

In targeted therapies of solid tumors the favourable initial results of the pivotal studies are rarely confirmed by subsequent publications and the discrepancy still favours the new drug, suggesting that many of these trials do not represent real population use and that some of them benefited from the  » improvement  » of their results before presentation to regulatory agencies.

 

 

Conference « Overconsumption, overtreatment » of Medicine Faculty of Bobigny, Seine Saint Denis (France)

Summary of a communication (April 2017)

 

 

SEE  THE POSTER http://surmedicalisation.fr/?page_id=4556#Gerard_DELEPINE1  IN FRENCH