ASCO 2010, New Drugs for Melanoma|May 15, 2011 9:39 pm

Ipilimumab at Plenary Session 2010

Today, for the first time anybody can remember, a melanoma study was presented at the ASCO plenary. It was very exciting for me to see my good friend Steve O’Day from The Angeles Clinic standing in front of what is literally a football stadium sized room that I estimate seats 15,000 people!

The study was presented in very straightforward manner. There are no questions at the plenary session, unlike in the disease specific oral abstract sessions.

There were not many new points of interest, since the NEJM article had become available yesterday. Basically, ipi showed an OS advantage over GP100 vaccine in advanced melanoma, 10.1 months vs 6.3 months. The addition of GP100 to ipi did not improve its efficacy. Ipi was consistently better than “control” in all measurable parameters.

The discussant, Dr. Vern Sondak, did a nice job of reviewing the melanoma treatment landscape and also the significance of the study results, as well as bringing up many of the questions that people have started to point out. He did not completely address those questions but of course that was not his role.

Overall, it is very exciting that a randomized clinical trial in Stage IV melanoma has, for the first time, shown a significant survival advantage for an experimental agent vs. a control. That being said, here are the questions that are floating around, like lightning bugs:

1. is GP100 a true placebo? Is it harmful? Would the survival in the control arm have been better with DTIC or a more standard “control” treatment?

2. There is another ipi trial that has not yet been unblinded due to lack of “events” (presumably deaths). This was also a large Phase III trial, comparing ipi/DTIC to DTIC alone. It was enrolled almost three years ago but has not yet had enough events, suggesting that the two arms have not had enough deaths to meet the pre-specified unblinding point. I don’t know their statistical design but we also don’t know if this trial is going to be signficant. What if it’s not? How would that affect our interpretation of the current trial? The doses are different, and the other trial is frontline therapy. Does that matter?

3. The current trial is second line therapy in an HLA restricted (HLA A2 pos) population. If approved by the FDA, will it be labeled as such? Will it be used for all Stage IV patients, regardless of HLA?(probably)

4. Can the significant toxicity be managed safely by community physicians without prior experience with the agent? Will there be early preventable deaths? By the way, the GP100 arm had 2.5% fatality rate thought to be related to therapy(!!)

5. I can’t shake the feeling that 6 and even 10 months are a little low for Stage IV melanoma in today’s world, particularly in specialty centers who may more aggressively pursue therapy. Looking through the posters today it seemed that almost all had median survivals more than ten months. Maybe the shorter term survivals were the result of having a larger multicenter trial.

Ultimately, as I noted elsewhere, it is refreshing to be critiquing a positive study for once, rather than lamenting another negative study. I believe that the truest measure of the power of the study will be revealed when the other study is unblinded.

Eric D. Whitman, MD

Senior Editor

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