The CheckMate 066 trial investigated nivolumab monotherapy as first-line treatment for patients with previously untreated BRAF wild-type advanced melanoma.,Five-year results are presented herein.,In this multicenter, double-blind, phase III study, 418 patients with previously untreated, unresectable, stage III/IV, wild-type BRAF melanoma were randomly assigned 1:1 to receive nivolumab 3 mg/kg every 2 weeks or dacarbazine 1,000 mg/m2 every 3 weeks.,The primary end point was overall survival (OS), and secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.,Patients were followed for a minimum of 60 months from the last patient randomly assigned (median follow-up, 32.0 months for nivolumab and 10.9 months for dacarbazine).,Five-year OS rates were 39% with nivolumab and 17% with dacarbazine; PFS rates were 28% and 3%, respectively.,Five-year OS was 38% in patients randomly assigned to dacarbazine who had subsequent therapy, including nivolumab (n = 37).,ORR was 42% with nivolumab and 14% with dacarbazine; among patients alive at 5 years, ORR was 81% and 39%, respectively.,Of 42 patients treated with nivolumab who had a complete response (20%), 88% (37 of 42) were alive as of the 5-year analysis.,Among 75 nivolumab-treated patients alive and evaluable at the 5-year analysis, 83% had not received subsequent therapy; 23% were still on study treatment, and 60% were treatment free.,Safety analyses were similar to the 3-year report.,Results from this 5-year analysis confirm the significant benefit of nivolumab over dacarbazine for all end points and add to the growing body of evidence supporting long-term survival with nivolumab mono-therapy.,Survival is strongly associated with achieving a durable response, which can be maintained after treatment discontinuation, even without subsequent systemic therapies.
This study aimed to investigate the prognostic value of HRAS mRNA expression in cutaneous melanoma.,Cutaneous melanoma is an aggressive cancer with an increasing incidence.,Few studies have focused on the transcriptional level of RAS isoforms (KRAS, NRAS, and HRAS) in cutaneous melanoma.,To gain further insight into RAS isoforms at transcriptional level, we obtained the cutaneous melanoma data from cBioPortal and investigated the RAS mRNA expression levels in different stages of melanoma and evaluated their correlation with clinical characteristics and patients' survival.,Furthermore, we retrieved and analyzed the coexpression data and performed pathway enrichment analysis.,Totally, 452 cutaneous melanoma cases were included in this study.,We found that lower HRAS expression level was associated with longer patient survival. 206 genes that negatively correlated with HRAS expression were positively correlated with KRAS and NRAS expression.,In contrast, no gene that positively correlated with HRAS expression was positively correlated with KRAS and NRAS expression.,In conclusion, our data showed that transcriptional regulation was different for the three RAS isoforms in cutaneous melanoma.,This study highlighted the prognostic value of HRAS mRNA expression and revealed that HRAS greatly differs from KRAS and NRAS at the transcriptional level.