YERVOY™ is the first and only treatment for pretreated patients with advanced melanoma with proven long-term survival beyond 2 years1,2,3,4,5
- Median OS benefit of 4 months1,2
- At 1 and 2 years, YERVOY™ nearly doubles the proportion of patients alive1,2
Study design of the registrational trial MDX010-020
This phase 3, double blind study enrolled patients with advanced (unresectable or metastatic) melanoma who had previously been treated. A total of 676 patients were randomized: 137 to the YERVOY™ monotherapy group, 403 to the YERVOY™ + gp100 group, and 136 to the gp100 alone group. The majority had received all 4 doses during induction. Thirty two patients received a re-induction dose: 8 in the YERVOY™ monotherapy group, 23 in the YERVOY™ + gp100 group, and 1 in the gp100 group. Duration of follow up ranged up to 55 months. Patients were randomized in a 3:1:1 ratio to receive YERVOY™ 3 mg/kg + an investigational gp100 peptide vaccine (gp100), YERVOY™ 3 mg/kg monotherapy, or gp100 alone. 1
*Due to the inclusion of the gp100 peptide vaccine comparator the study was restricted to patients with HLA-A2*0201 genotype.
† Because of the minimal amount of data re-induction is not within label. An additional four doses of treatment were offered to patients who developed progressive disease (PD) after initial clinical response (partial response [PR] or complete response [CR] or after stable disease (SD) lasting longer than 3 months from initial tumor assessment.
Patients received YERVOY™ every 3 weeks for 4 doses as tolerated (induction therapy). Patients with apparent tumour burden increase before completion of the induction period were continued on induction therapy as tolerated if they had adequate performance status. Assessment of tumour response to YERVOY™ was conducted after completion of induction therapy.1
- The primary endpoint was overall survival (OS) in the YERVOY™+ gp100 group vs. the gp100 group. 1,2
- Study 020 is the first phase 3 study in metastatic melanoma that set the standard of overall survival as the primary endpoint. 1,2
- OS in the YERVOY™+ gp100 group vs. the YERVOY™ monotherapy group and in the YERVOY™ monotherapy group vs. the gp100 group.
- Other secondary endpoints included best overall response rate (BORR) up to Week 24 and duration of response.
Baseline characteristics were well balanced across groups.* The median age was 57 years. The majority (71-73%) of patients had M1c stage disease and 37-40% of patients had an elevated LDH at baseline. A total of 77 patients had a history of previously treated brain metastases. 1
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* Exclusion criteria included anyone <18 years; having had any other cancer from which the patient had been disease free for <5 years; primary ocular melanoma; previous receipt of anti-CTLA-4 antibody or cancer vaccine; autoimmune disease; active untreated metastases in the central nervous system; lactation or pregnancy; concomitant treatment with any nonstudy anticancer therapy or immunosuppressive agent; long-term use of systemic corticosteroids; patients without liver metastasis with a baseline AST >5 × ULN; patients with liver metastasis with a baseline AST >5 × ULN, and patients with a baseline total bilirubin ≥3 × ULN were also excluded.
The YERVOY™ containing regimens demonstrated a statistically significant advantage over the gp100 control group in OS. The hazard ratio (HR) for comparison of OS between YERVOY™ monotherapy and gp100 was 0.66 (95% CI: 0.51, 0.87; p = 0.0026).
By subgroup analysis, it has been shown that the observed OS benefit was consistent within most of the subgroups of patients (M [metastases]-stage, prior interleukin-2, baseline lactate dehydrogenase, age, and sex). However, for women above 50 years of age, the data supporting an OS benefit of YERVOY™ treatment were limited. The efficacy of YERVOY™ for women above 50 years of age is therefore uncertain. As the subgroups analysis includes only small numbers of patients, no definitive conclusions can be drawn from these data. 1
1. YERVOY™ Summary of Product Characteristics.
2. Hodi FS et al. Improved Survival with Ipilimumab in Patients with Metastatic Melanoma. N Engl J Med. 2010;363(8):711-23.
3. European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) Assessment Report For YERVOY (ipilimumab) 24 October 2013.
4. McDermott D et al. Ann Oncol 2013;24:2694-8.
5. Eggermont AM et al. Eur J Cancer. 2011;47:2150–7.