Results of a multicenter, randomized, double‐blind phase 2/3 study of lenalidomide in the treatment of pretreated relapsed or refractory metastatic malignant melanoma

Abstract

BACKGROUND:The results of an international, multicenter, randomized, double-blind, controlled study assessing the efficacy and safety of lenalidomide treatment in patients with refractory stage IV metastatic malignant melanoma are reported. METHODS: The study compared treatment with lenalidomide (25 mg/d on Days 1-21 of a 28-day cycle) to placebo in 306 patients with metastatic malignant melanoma. Treatment was continued until progression of disease or unacceptable toxicity. RESULTS: There were no significant differences between lenalidomide and placebo in overall survival (median 5.9 months vs 7.4 months, respectively; P ¼ .32), time to progression (median 3.0 months vs 2.1 months; P ¼ .19), or Response Evaluation Criteria in Solid Tumors tumor response (5.3% vs 5.8%; P ¼ .82). None of the patients given placebo discontinued treatment because of treatment-related adverse events, compared with 4.6% of those treated with lenalidomide. Treatment-related myelosuppression was observed in 2.0% of patients treated with placebo and 7.3% of patients treated with lenalidomide. CONCLUSIONS: This study showed that treatment with lenalidomide (25 mg/d) has a manageable safety profile in patients with previously treated metastatic malignant melanoma but no benefit in tumor response, time to progression, or overall survival in these patients. Future trials for treatment of metastatic malignant melanoma with lenalidomide should focus on its use in combination therapies.

Role of Angiogenesis and Microenvironment in Melanoma Progression

“…Despite the fact that clinical response was not the primary end-point of the study and that the patients had not responded to prior therapy, clear evidence of drug activity in rapidly progressing malignant melanoma with one partial response and two minor responses of visceral disease have been obtained. Subsequent studies (Glaspy et al, 2009;Eisen et al, 2010) have demonstrated that treatment with Lenalidomide (25 mg/d) has a manageable safety profile in patients with previously treated metastatic malignant melanoma. Although no benefit in tumour response, time to progression, or overall survival has been achieved in these patients, future trials for treatment of metastatic malignant melanoma with Lenalidomide should be conduct which focus its use in combination therapies (Lu et al, 2009).…”

Lenalidomide in solid tumors

“…In another phase II/III multicenter, randomized study, lenalidomide at 25 mg/day on days 1-21 of a 28-day cycle was compared with placebo in patients with stage IV refractory metastatic melanoma [35]. In 128 lenalidomidetreated patients, no differences in overall response rate, survival, or time to progression were noted between patients who received lenalidomide vs. placebo (p = 0.82) [35].…”

“…In 128 lenalidomidetreated patients, no differences in overall response rate, survival, or time to progression were noted between patients who received lenalidomide vs. placebo (p = 0.82) [35].…”

Systematic Review and Network Meta-Analysis of Overall Survival Comparing 3 mg/kg Ipilimumab With Alternative Therapies in the Management of Pretreated Patients With Unresectable Stage III or IV Melanoma

“…1). However, comparing across classes implies that only RCTs evaluating treatments within two or more classes could be included for analysis, reducing our evidence base from 38 to 15 studies and excluding landmark trials such as that of Eisen et al [45], which is the only RCT in patients with metastatic malignant pretreated melanoma that is placebo controlled, and as such did not provide a link with the drug classes in the other studies. Table 2 provides an overview of the study and patient characteristics of the 15 studies included in the NMA.…”