| General information |
| Database: | DB00009 |
| Objective: | Cytotoxic Tlymphocyteassociated antigen 4 (CTLA4) blockade with ipilimumab prolongs survival in patients with metastatic melanoma. CTLA4 blockade and granulocytemacrophage colonystimulating factor (GMCSF)secreting tumor vaccine combinations demonstrate therapeutic synergy in preclinical models. A key unanswered question is whether systemic GMCSF (sargramostim) enhances CTLA4 blockade.OBJECTIVE:To compare the effect of ipilimumab plus sargramostim vs ipilimumab alone on overall survival (OS) in patients with metastatic melanoma |
| Authors: | Hodi FS, et al |
| Title: | Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. |
| Journal: | JAMA. |
| Year: | 2014 |
| PMID: | 25369488 |
| Trial Design |
| Clinical Trial Id: | NCT01134614 |
| Agent: | ipilimumab
|
| Target: | Cytotoxic Tlymphocyte antigen 4 (CTLA4)
|
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Ipilimumab+ sargramostim |
| Study Type: | a USbased phase II randomized clinical trial |
| Key Patients Feature: | patients with unresectable stage III or IV melanoma, at least 1 prior therapy, no central nervous system metastases, and ECOG performance status of 0 or 1 |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | ipilimumab plus sargramostim vs ipilimumab alone |
| Treatment Info: | patients were randomized to receive ipilimumab, 10 mg/kg, intravenously on day 1 plus sargramostim, 250 ¦Ìg subcutaneously, on days 1 to 14 of a 21day cycle (n=123) vs ipilimumab alone (n=122). Ipilimumab treatment included induction for 4 cycles followed by maintenance every fourth cycle. |
| Primary End Point: | comparison of length of OS. |
| Secondary End Point: | progression free survival (PFS), response rate, safety, and tolerability. |
| Patients Number: | 245 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | There was no difference in PFS. Median PFS for ipilimumab plus sargramostim was 3.1 months (95% CI, 2.94.6) vs 3.1 months (95% CI, 2.94.0) for ipilimumab alone. |
| Median OS A vs. C: | Median OS as of December 2012 for ipilimumab plus sargramostim was 17.5 ms (95% CI, 14.9not reached) vs 12.7 ms (95% CI, 10.0not reached) for ipilimumab. The 1year survival rate for ipilimumab plus sargramostim was 68.9% (95% CI, 60.6%85.5%) compared to 52.9% (95% CI, 43.6%62.2%) for ipilimumab alone (stratified logrank 1sided P=0.01; mortality hazard ratio 0.64 [1sided 90% repeated CI, not applicable0.90]). A planned interim analysis was conducted at 69.8% of expected events (104 observed with 149 expected deaths). Planned interim analysis using the O'BrienFleming boundary was crossed for improvement in OS. |
| Adverse Event(agent arm): | Grade 3 to 5 adverse events occurred in 44.9% (95% CI; 35.8%54.4%) of patients in the ipilimumab plus sargramostim group vs 58.3% (95% CI, 49.0%67.2%) of patients in the ipilimumabalone group. |
| Conclusions: | Among patients with unresectable stage III or IV melanoma, treatment with ipilimumab plus sargramostim vs ipilimumab alone resulted in longer OS and lotheyr toxicity, but no difference in PFS. These findings require confirmation in larger studies with longer followup. |