Long-term real-world experience with ipilimumab and non-ipilimumab therapies in advanced melanoma: the IMAGE study

Abstract

Background Ipilimumab has shown long-term overall survival (OS) in patients with advanced melanoma in clinical trials, but robust real-world evidence is lacking. We present long-term outcomes from the IMAGE study (NCT01511913) in patients receiving ipilimumab and/or non-ipilimumab (any approved treatment other than ipilimumab) systemic therapies. Methods IMAGE was a multinational, prospective, observational study assessing adult patients with advanced melanoma treated with ipilimumab or non-ipilimumab systemic therapies between June 2012 and March 2015 with ≥3 years of follow-up. Adjusted OS curves based on multivariate Cox regression models included covariate effects. Safety and patient-reported outcomes were assessed. Results Among 1356 patients, 1094 (81%) received ipilimumab and 262 (19%) received non-ipilimumab index therapy (systemic therapy [chemotherapy, anti–programmed death 1 antibodies, or BRAF ± MEK inhibitors], radiotherapy, and radiosurgery). In the overall population, median age was 64 years, 60% were male, 78% were from Europe, and 78% had received previous treatment for advanced melanoma. In the ipilimumab-treated cohort, 780 (71%) patients did not receive subsequent therapy (IPI-noOther) and 314 (29%) received subsequent non-ipilimumab therapy (IPI-Other) on study. In the non-ipilimumab–treated cohort, 205 (78%) patients remained on or received other subsequent non-ipilimumab therapy (Other-Other) and 57 (22%) received subsequent ipilimumab therapy (Other-IPI) on study. Among 1151 patients who received ipilimumab at any time during the study (IPI-noOther, IPI-Other, and Other-IPI), 296 (26%) reported CTCAE grade ≥ 3 treatment-related adverse events, most occurring in year 1. Ipilimumab-treated and non-ipilimumab–treated patients who switched therapy (IPI-Other and Other-IPI) had longer OS than those who did not switch (IPI-noOther and Other-Other). Patients with prior therapy who did not switch therapy (IPI-noOther and Other-Other) showed similar OS. In treatment-naive patients, those in the IPI-noOther group tended to have longer OS than those in the Other-Other group. Patient-reported outcomes were similar between treatment cohorts. Conclusions With long-term follow-up (≥ 3 years), safety and OS in this real-world population of patients treated with ipilimumab 3 mg/kg were consistent with those reported in clinical trials. Patient-reported quality of life was maintained over the study period. OS analysis across both pretreated and treatment-naive patients suggested a beneficial role of ipilimumab early in treatment. Trial registration ClinicalTrials.gov, NCT01511913. Registered January 19, 2012 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01511913

Real‐world evidence of biological agents in dermatology: A review of its applications, advantages, and limitations

“…For example, in a multinational, prospective, observational study that involving adult patients, who were followed up for at least 3 years, with advanced melanoma treated with ipilimumab or non‐ipilimumab systemic therapies, the 3‐year OS rate was 28% in the ipilimumab‐treated cohort and 25% in the non‐ipilimumab–treated cohort, which was consistent with efficacy in ipilimumab clinical trials. Similar results can be captured between non‐ipilimumab‐treated patients who received subsequent ipilimumab therapy and who continued to take non‐ipilimumab therapy, which proved positive effects on patients switching to ipilimumab treatment 11 . In another study conducted from 23 Canadian medical centers focused on the efficacy of adalimumab on hidradenitis suppurative, 69% of the 138 patients achieved Hidradenitis Suppurativa Clinical Response (HiSCR) at week 24, which increased to 82% and 75% at week 52 in patients with medium and high AN count.…”

“…Similar results can be captured between non-ipilimumab-treated patients who received subsequent ipilimumab therapy and who continued to take non-ipilimumab therapy, which proved positive effects on patients switching to ipilimumab treatment. 11 In another study conducted from 23 Canadian medical centers focused on the efficacy of adalimumab on hidradenitis suppurative, 69% of the 138 patients achieved Hidradenitis Suppurativa Clinical Response (HiSCR) at week 24, which increased to 82% and 75% at week 52 in patients with medium and high AN count. The outcomes confirmed previous two 12-week phase three multicenter trials in a 12-month period with abundant patients who were not eligible for RCTs.…”

Health-related quality of life in patients with advanced melanoma treated with ipilimumab: prognostic implications and changes during treatment

“…Clinically meaningful worsening in HRQL in patients receiving ipilimumab monotherapy was detected in the MDX010-20 25 and KEYNOTE-006 26 trials, with similar findings reported in an observational study in real-world patients with metastatic melanoma. 27 The CheckMate 067 trial, 28 however, noted no clinically meaningful changes in the ipilimumab arm, but compliance was <70% at treatment completion.…”

Research Progress of Immune Checkpoint Inhibitors in Melanoma

“…Ipilimumab was the first FDA-approved antibody for melanoma, and has been proved to have a long-term survival advantage for patients with advanced cutaneous melanoma [14]. A prospective real-world study of ipilimumab and non-ipilimumab treatment in patients with advanced melanoma showed that the 3-year OS rate was 28% in the ipilimumab-treated cohort and 25% in the nonipilimumab-treated cohort [15]. This demonstrates that although ipilimumab is no longer commonly used as first-line monotherapy for patients with advanced melanoma, ipilimumab still gains benefit and has no detrimental impact on long-term quality of life (QoL).…”