Friday, June 30, 2017

Outcomes for melanoma patients ~ clinical trials vs standard of care

I thought this was an interesting outcome to look at:

Outcomes in Melanoma Patients Treated with BRAF/MEK-Directed Therapy or Immune Checkpoint Inhibition Stratified by Clinical Trial versus Standard of Care. Goldman, Tchack, Robinson...Pavick, et al.  Oncology. 2017 Jun 10.

Since 2011, metastatic melanoma treatment has evolved with commercial approval of BRAF- and MEK-targeted therapy and CTLA-4- and PD-1-blocking antibodies (immune checkpoint inhibitors, ICI). While novel therapies have demonstrated improved prognosis in clinical trials, few studies have examined the evolution of prognosis and toxicity of these drugs among an unselected population. We assess whether survival and toxicity reported in trials, which typically exclude most patients with brain metastases and poor performance status, are recapitulated within a commercial access population.
182 patients diagnosed with stage IV melanoma from July 2006 to December 2013 and treated with BRAF- and/or MEK-targeted therapy or ICI were prospectively studied. Outcomes and clinicopathologic differences between trial and commercial cohorts were assessed
Patients receiving commercial therapy (vs. on trial) had poorer prognostic features (i.e., brain metastases) and lower median overall survival (mOS) when assessed across all treatments (9.2 vs. 17.5 months). While toxicity within trial and commercial cohorts did not differ, patients who experienced toxicity had increased mOS, irrespective of stratification by trial status or therapy.
Metastatic melanoma patients receiving commercial treatment may represent a different clinical population with poor prognostic features compared to trial patients. Toxicity may prognosticate treatment benefit. this report it is noted that folks who were NOT in a clinical trial, no matter if they were being treated with immunotherapy OR targeted therapy, did less well.  The researchers acknowledge that it is likely that folks who were in poorer health were the peeps who made up more of the population in the standard of care group.  Heaven knows....I have yelled and yelled about the exclusions that are so very often baked into clinical trials...and my firm belief that Big Pharma's (and even some researcher's) desire to make their outcomes look good drives much of this.  For far too long, folks who are in dire straits with significant tumor burden, prior treatments, and certainly CNS disease have been automatically excluded from clinical trials.  Consequently, when those folks finally get treatment from their local doc, outside of a clinical trial, they do less well when compared to the cream of the crop patients that the trials deign to include.

However, I feel there may be one other component relevant to this outcome ~ expertise. Participating in a clinical trial comes with some significant risks, expense, chaos and craziness inherent to the process. But, much of the time, it also comes with state of the art facilities, research labs, and renowned experts in the field in question who are at the top of their game and on top of the latest data and intel.  I fear that local oncs are not always well versed and experienced in the treatments they are providing.  They may fail to recognize symptoms of both progression and side effects as rapidly as a more expert clinician would.  Equally importantly, they may not allow the time needed for a response when dealing with immunotherapy, leading to the abandonment of a potentially good treatment outcome before the patient can attain the response needed, thus causing an unnecessary bad outcome.

As the article notes, these therapies have now been on the market, and therefore in the arsenal of melanoma treatments available for use by local oncologists, for 6 years.  Hopefully, local learning curves have been climbed and trial requirements will soon be adjusted in ways that make standard of care what it really should be for all melanoma patients. - c

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