Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma

Abstract

Purpose: To provide a more precise estimate of long-term survival observed for ipilimumab-treated patients with advanced melanoma, we performed a pooled analysis of overall survival (OS) data from multiple studies.

Methods: The primary analysis pooled OS data for 1,861 patients from 10 prospective and two retrospective studies of ipilimumab, including two phase III trials. Patients were previously treated (n = 1,257) or treatment naive (n = 604), and the majority of patients received ipilimumab 3 mg/kg (n = 965) or 10 mg/kg (n = 706). We also conducted a secondary analysis of OS data (n = 4,846) with an additional 2,985 patients from an expanded access program. OS rates were estimated using the Kaplan-Meier method.

Results: Among 1,861 patients, median OS was 11.4 months (95% CI, 10.7 to 12.1 months), which included 254 patients with at least 3 years of survival follow-up. The survival curve began to plateau around year 3, with follow-up of up to 10 years. Three-year survival rates were 22%, 26%, and 20% for all patients, treatment-naive patients, and previously treated patients, respectively. Including data from the expanded access program, median OS was 9.5 months (95% CI, 9.0 to 10.0 months), with a plateau at 21% in the survival curve beginning around year 3.

Conclusion: To our knowledge, this is the largest analysis of OS to date for ipilimumab-treated patients with advanced melanoma. We observed a plateau in the survival curve, beginning at approximately 3 years, which was independent of prior therapy or ipilimumab dose. These data add to the evidence supporting the durability of long-term survival in ipilimumab-treated patients with advanced melanoma.

Trial registration: ClinicalTrials.gov NCT00032045 NCT00058279 NCT00077532 NCT00094653 NCT00135408 NCT00261365 NCT00289627 NCT00289640 NCT00324155 NCT00623766.

Fig 1.

Primary analysis of pooled overall survival (OS) data. Individual patient data were pooled from 10 prospective trials and two retrospective, observational studies of ipilimumab in metastatic melanoma (n = 1,861). Median OS was 11.4 months (95% CI, 10.7 to 12.1 months) with a 3-year survival rate of 22% (95% CI, 20% to 24%). Crosses indicate censored patients.

Fig 2.

Subset analysis of overall survival (OS) by prior therapy. Nonrandomized subset analysis of OS in treatment-naive (n = 604) and previously treated (n = 1,257) patients with metastatic melanoma who received ipilimumab in 10 prospective trials and two retrospective, observational studies. Median OS was 13.5 months (95% CI, 11.9 to 15.4 months) for treatment-naive patients and 10.7 months (95% CI, 9.6 to 11.4 months) for previously treated patients, with 3-year survival rates of 26% (95% CI, 21% to 30%) and 20% (95% CI, 18% to 23%), respectively. Crosses indicate censored patients.

Fig 3.

Subset analysis of overall survival (OS) by ipilimumab dose. Nonrandomized subset analysis of OS in patients who received ipilimumab at 3 mg/kg (n = 965), 10 mg/kg (n = 706), or other dosing regimens (n = 190) in 10 prospective trials and two retrospective, observational studies. Median OS was 11.4 months (95% CI, 10.3 to 12.5 months) for 3 mg/kg, 11.1 months (95% CI, 9.9 to 13.0 months) for 10 mg/kg, and 12.4 months (95% CI, 10.4 to 15.1 months) for other dosing regimens; the 3-year survival rates were 21% (95% CI, 17% to 24%), 24% (95% CI, 21% to 28%), and 20% (95% CI, 14% to 26%), respectively. Crosses indicate censored patients.

Fig 4.

Pooled overall survival (OS) analysis with expanded access protocol (EAP) data. Individual patient survival data were pooled from 1,861 patients with metastatic melanoma from 12 clinical investigations of ipilimumab and 2,985 patients with metastatic melanoma from a US EAP (n = 4,846). Median OS was 9.5 months (95% CI, 9.0 to 10.0 months) with a 3-year survival rate of 21% (95% CI, 20% to 22%). Crosses indicate censored patients.