Addition of GP100 Vaccine to Interleukin-2 Improves Clinical Response in Advanced Melanoma

DynaMed Weekly Update - Volume 6, Issue 23

There is currently little evidence for the efficacy of vaccines to limit the progression of metastatic cancer. Vaccine treatment (sipuleucel-T) has been associated with increased survival in men with prostate cancer ( N Engl J Med 2010 Jul 29;363(5):411). But a recent high-quality trial investigating the GP100 vaccine in patients with metastatic melanoma found no survival benefit for the combination of vaccine plus ipilimumab compared to ipilimumab alone and found reduced survival in patients receiving vaccine alone (N Engl J Med 2010 Aug 19;363(8):711). However, a new trial indicates that GP100 plus interleukin-2 increases clinical response, delays recurrence, and may improve survival.

A total of 185 patients with stage III-IV melanoma without brain metastases were randomized to GP100 plus incomplete Freund’s adjuvant in combination with interleukin-2 vs. interleukin-2 only. The GP100 group received the vaccine once per 3-week cycle. All patients had interleukin-2 at a dose of 720,000 units/kg IV bolus every 8 hours up to 12 doses per cycle. Complete clinical response was defined as disappearance of all lesions.

At mean follow-up of 41.5 months, the GP100 group had significantly higher rates of both complete clinical response (9% vs. 1%, p = 0.01, NNT 13) and any clinical response (16% vs. 6%, p = 0.03, NNT 10), and had longer progression-free survival (median 2.2 months vs. 1.6 months, p = 0.008) (level 3 [lacking direct] evidence). Also, there was a trend toward increased overall survival in the GP100 group (median 17.8 months vs. 11.1 months, p = 0.06) (level 2 [mid-level] evidence). The risk of arrhythmias was significantly increased in the GP100 group (15% vs. 2%, p< 0.002, NNH 7) (N Engl J Med 2011 Jun 2;364(22):2119).

For more information, see the Melanoma topic in DynaMed.