Thoughts on Trials and Clinical Research by Melanoma Big Dogs

Y'all know I've been yelling about this for years:

Most recently here:  The trial of trials

And previously ~
2016:
The Problem with Clinical Trials

Medical studies in children go unpublished!!! Here we go AGAIN!!!

2015:
A beautiful lady, with eloquent, though heartbreaking words re: clinical trials....

2014:
Clinical Trials and Patient Rights...An oxymoron????

Patient rights in a clinical trial. An oxymoron???? Redux...

Challenges in Conducting Clinical Research on Patients With Advanced Melanoma.  Cancer J. 2017 Jan/Feb.  Sznol.

Unprecedented advances in the treatment of melanoma and the large number of investigational therapies entering clinical studies not only represent outstanding achievements, but also create major challenges for clinical research in melanoma. The challenges for accrual and for developing important new data in trials include the relatively low incidence of melanoma compared with other diseases, a shrinking pool of patients for trials because of the high efficacy of standard of care therapy, requirements for larger studies and longer duration of follow-up to detect signals of activity or establish efficacy, and suboptimal predictive biomarkers for the vast number of new combinations and new agents. The cost of new treatments remains a major concern, particularly because current standard of care involves doublets of targeted therapy or immune therapy, and clinically meaningful further increases in efficacy may require development of triplets or larger multidrug combinations. Toxicities of the current doublets, particularly for immune therapy, may limit development of some multidrug regimens or may require novel solutions such as sequencing or alternating schedules. The activity of first-line therapies may push development of new drugs or combinations into the second-line setting or into subgroups with suboptimal response to the first-line doublets as identified by predictive clinical variables or tissue biomarkers.

Clinical Trial Design and Endpoints for Stage IV Melanoma in the Modern Era.  Izar, Regan, McDermott.  Cancer J. 2017 Jan/Feb.

Immunotherapies and targeted therapies for the treatment of metastatic or advanced melanoma produce unique patterns of antitumor response. Conventional outcome measures, such as median progression-free and overall survival, may not be ideally suited to identify all patients who derive a benefit from such therapies. Therefore, the introduction of additional endpoint measures, such as milestone comparisons, may be necessary to characterize the potential benefit of such treatment approaches. Immune checkpoint inhibitors induce durable responses in a portion of patients that may continue after treatment cessation. Measuring the associated treatment-free interval, treatment-free survival, and associated patient-reported outcomes could provide important information when implemented in prospective clinical trials. In this article, we discuss the limitations of current endpoint measures and the potential advantage of using novel endpoints and how these might be used in designing clinical trials to address critical unanswered questions for patients with metastatic melanoma.  

YES!!!  While PFS and OS are certainly important milestones, as noted here:  After stopping anti-PD1 treatment...how long can melanoma patients maintain a complete response????    Identifying duration of response and patient outcomes are essential for progress and the development of intelligent treatment choices.

While wheels always turn more slowly than I'd like them to, I have to believe we will get it right....soon!  Thanks to all the ratties!  Hang tough! - love, c