Data from MAINSAIL trial provides us with a cautionary tale ? THE ...

In November 2011 we reported that Celgene had terminated the Phase III, MAINSAIL trial of lenalidomide (Revlimid^?) in combination with docetaxel and prednisone?in treatment of men with chemotherapy-naive, metastatic, castration-resistant prostate cancer (mCRPC) for lack of efficacy.

The results of this trial were actually reported at the annual meeting of the European Society for Medical Oncology (ESMO), held in Vienna, Austria, at the end of September. The presentation by Daniel Petrylak, MD, was reported in December 15 issue of The ASCO Post.

The basic results of the trial ? which showed that lenalidomide + docetaxel + prednisone was no more effective and had greater toxicity than standard docetaxel + prednisone chemotherapy ? were expected based on the decision to stop the trial nearly a year earlier. What was, perhaps, less expected was expressed in an expert commentary by Robert Jones, MD.

Effectively, Dr. Jones argues that this Phase III trial should never have been carried out without a prior Phase II trial to demonstrate proof of concept. He points out that:

• Preclinical data suggested that lenalidomide + docetaxel + prednisone would be more toxic than docetaxel + prednisone.
• There were no studies demonstrating proof of the concept that adding lenalidomide to docetaxel + prednisone would have greater effectiveness.
• The first, planned interim analysis was conducted so late that 100% of patients had already been enrolled into the trial.

He states that,

All phase?III trials combining docetaxel with novel agents have been negative to date. This is also the fourth negative trial that fails to harness the power of antiangiogenic therapy in prostate cancer.

He then goes on to add that, in his opinion,

? future combination studies should demand proof of concept. We have an obligation to patients to minimize avoidable risks. Randomized phase?II trials should probably be required prior to initiating phase?III studies. We could consider better use of early stopping rules. We are still challenged by lack of a robust endpoint for early stopping [of trials like the MAINSAIL study].

Dr. Jones makes it very clear that these statements are being made with the benefit of hindsight, but they do raise important questions about whether sufficient care is being taken today to ensure that patient risk is being suitably addressed in the design of trials of new therapies for men with last stage prostate cancer, and whether the forms patients are asked to read and sign prior to participating in such trials are really sufficiently straightforward about what is and is not known.

Lenalidomide has been shown to have excellent activity and effectiveness in the treatment of other forms of cancer. However, it does have to be noted that activity and safety in Cancer A is no sort of guarantee of activity and safety in Cancer B. The ?New? Prostate Cancer InfoLink is as guilty as everyone else for not asking early on what data was available to justify the idea that adding lenalidomide to docetaxel + prednisone in the treatment of men with chemotherapy-naive mCRPC.

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Filed under: Drugs in development, Living with Prostate Cancer, Management, Treatment Tagged: | castration-resistant, chemotherapy-na?ve, docetaxel, lenalidomide, MAINSAIL, mCRPC, metastatic

Source: http://prostatecancerinfolink.net/2013/01/02/data-from-mainsail-trial-provides-us-with-a-cautionary-tale/

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