|WikiProject Medicine||(Rated Start-class, Low-importance)|
I'm parking citations here until I get back to work on this story some more.
I thought I could find a simple explanation specifically of PFS vs. OS in the BMJ, but I'm still looking. The discussion of PFS in BMJ (and other journals) seems to be in the context of specific drugs that were approved for specific indications on the basis of PSF and not OS, such as bevacizumab.
Many cancer drugs approved on the basis of progression-free surivival have failed to show improvements in overall survival in postmarketing surveillance. Measuring overall survival will increase study size, cost, and time to drug availability, but they will ensure that drugs are effective. For example, a 69yo man with refractory advanced kidney cancer joined the trial for axitinib, but 4 months later died from GI bleeding. The FDA approved axitinib, a $10,000/mo drug, without proof that it would improve survival or QOL.
http://www.nejm.org/doi/full/10.1056/NEJMp1106984 Changing End Points in Breast-Cancer Drug Approval — The Avastin Story
http://www.bmj.com/content/343/bmj.d4244 FDA committee votes to withdraw bevacizumab for breast cancer
http://www.bmj.com/content/343/bmj.d4946 Potential withdrawal of bevacizumab for the treatment of breast cancer Why is progression-free survival a controversial surrogate end point? Traditionally in the US an improvement in overall survival was a clear and unambiguous end point that needed to be met before a drug was deemed suitable for approval for everyday use. Progression-free survival has been suggested as an alternative in the past five years and is increasingly used as the primary end point in randomised clinical trials. However, a poor correlation exists between response rates and progression-free survival as surrogate end points for overall survival in metastatic breast cancer.5 In the E2100 trial, bevacizumab combined with paclitaxel had among the best results of any chemotherapy regimen used in terms of response rates or progression-free survival but it did not translate into an overall survival advantage in this unselected population.
http://jco.ascopubs.org/content/25/33/5153.full Toward Progression-Free Survival As a Primary End Point in Advanced Colorectal Cancer OS is usually defined as time to death from any cause and may be considered a composite end point based on the cause of death where the event is the first of death related to the same cancer, death related to another cancer, death related to treatment, or death resulting from other causes. PFS is a composite end point where the event is the first of progression resulting from increasing size of tumor, progression resulting from formation of a new tumor, death related to the same cancer, death related to another cancer, death related to treatment, or death resulting from other causes. The component events are listed in Table 1 for the PFS and OS end points along with their relationship to the disease process under study or the therapies being studied.
This article is marred by the fact that it does not precisely define "Progression free survival".
In particular, the article needs to specify precisely when a patient has been deemed to "progress". It appears from an amateur and cursory glance at the literature that subject to some conditions the prevailing definition is a 20% increase in sum-of-diameters of target tumors from the lowest reading on study, which may or may not be the patient's first reading on study.
It would be nice if an expert would verify this and make this article more precise!
There is no single definition nor a single measurement of PFS. It is instead a collection of various measurements and imaging techniques that are collected and simplified into the single value "Progression Free Survival", either by the primary investigators or by an independent group. For solid tumors, the RECIST guidelines have been created by the European Organization for Research and Treatment of Cancer to help unify measurements of PFS in the study of chemotherapeutic agents.
However, PFS has not been strictly limited to studying solid tumors. Just one example, PFS has been used as a primary end point in a study on Cystic Fibrosis: http://erj.ersjournals.com/content/34/5/1079.full Sheldahl (talk) 16:07, 18 July 2015 (UTC)
- John Fauber, Elbert Chu (Oct 27, 2014). "The Slippery Slope: Is a Surrogate Endpoint Evidence of Efficacy?". Milwaukee Journal Sentinel/MedPage Today.