Biotech Values

[Biowatch]

Is their one cancer drug for any solid tumor which has met the PFS
endpoint with irrefutable exactitude?

Do you mean, "Is there any cancer drug for any solid tumor..."

Yes: "Advanced colorectal and advanced ovarian cancers seem to be the only two tumor types for which data supporting the surrogacy of PFS for OS have been demonstrated..."
Journal of Clinical Oncology 30, no. 10 (April 2012) 1030-1033.

Solid tumors are still hard to treat. Immunotherapy hasn't made much headway yet.

Progression free survival seems like a more meaningful metric than the fate of surrogate markers. However, increasing PFS does not always imply greater Overall Survival.
Progression-Free Survival: Meaningful or Simply Measurable?
Journal of Clinical Oncology 30, no. 10 (April 2012) 1030-1033.

You can knock back the level of a given surrogate without any affect on the patient's health if it is a "meaningless" biomarker. In prostate cancer, it is not clear what biomarker works well.

For further comments on PFS versus OS, see:
Progression-Free Survival: Helpful Biomarker or Clinically Meaningless End Point?
Journal of Clinical Oncology 33, no. 1 (January 2015) 4-6.



Progression-Free Survival: Meaningful or Simply Measurable?
Journal of Clinical Oncology 30, no. 10 (April 2012) 1030-1033.

Advanced colorectal and advanced ovarian cancers seem to be the only two tumor types for which data supporting the surrogacy of PFS for OS have been demonstrated... even for colorectal and ovarian cancers, some caution should be exercised with regard to whether the association between PFS and OS as defined in the cytotoxic era can be extrapolated to the era of contemporary oncology with novel targeted molecular therapies...

...It seems clear that the growing use of PFS as a primary end point in many RCTs of advanced solid tumors has not been based on evidence of its surrogacy for either OS or QOL. Indeed, one wonders if we have not been misled into believing that because a definition for progression exists (albeit created for another purpose), and we can measure it, there must be some importance to finding it prolonged. By doing this, we have made our trials shorter, evaluated new agents more quickly, and, coincidentally, likely had more positive trials (and new agents approved) than would have been the case had OS been used. This trend is worrying, because the adoption of new therapies through studies using an end point that effectively lowers the bar for declaring new drugs to be active may, in fact, be offering little of meaning to our patients.

It is time for the oncology community and regulatory agencies to take a hard look at PFS and challenge its growing use as a primary efficacy end point. There should be good evidence for its ability to predict improved QOL or OS improvements if it is to play a central role in defining new standards of care. If it does not have these properties, we must measure the true end points of importance to our patients, and not something that has as its chief advantage ease of measurement or speed of trial completion.

We should not let clinical cancer research fall victim to what has been termed the McNamara fallacy (after US secretary of defense in 1960s, known for quantifying progress of war in Vietnam by easily measurable metrics such as body counts), which states first, measure whatever can be easily measured; second, disregard that which cannot be measured easily; third, presume that which cannot be measured easily is not important; and finally, presume that which cannot be measured easily does not exist.40 Let us not assign meaning to something that is merely measureable, while failing to measure, or failing to make decisions based on, those things that are truly important.

See accompanying articles on pages 1114 and 112