Efficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: A phase II study

Abstract

Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T‐cell activation through overexpression of the inhibitory receptor programmed death 1 (PD‐1) ligands. The PD‐1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has shown promising anticancer activity in various cancers. We carried out a single‐arm, open‐label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma. Twenty‐four patients with stage III/IV or recurrent melanoma were enrolled and received i.v. nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate evaluated by an independent radiology review committee. The independent radiology review committee‐assessed overall response rate was 34.8% (90% confidence interval, 20.8–51.9), and the overall survival rate at 18 months was 56.5% (90% confidence interval, 38.0–71.4). Treatment‐related adverse events (AEs) of grade 3 or 4 only occurred in three patients (12.5%). Two patients discontinued nivolumab because of AEs, but all AEs were considered manageable by early diagnosis and appropriate treatment. Subgroup analyses showed that nivolumab was clinically beneficial and tolerable regardless of BRAF genotype, and that patients with treatment‐related select AEs and with vitiligo showed tendency for better survival. In conclusion, nivolumab showed favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma, with or without BRAF mutations. (Trial registration no. JapicCTI‐142533.)

Immune‐related adverse events correlate with improved survival in patients with advanced mucosal melanoma treated with nivolumab: A single‐center retrospective study in Japan

“…The results of these studies were consistent with the hypothesis that irAE are associated with a better outcome after this therapy. Several studies including patients treated with nivolumab for melanoma reported that the antitumor response was stronger in those exhibiting irAE . To our knowledge, however, similar findings have not yet been reported in patients with MM who exhibit worse response to nivolumab compared with those with cutaneous melanoma …”

“…However, the efficacy of nivolumab monotherapy in MM was not known because of its rarity. In Japanese clinical trials of anti‐PD‐1 monotherapy for advanced melanoma, the ORR for nivolumab and pembrolizumab was 34.8% and 24.3%, respectively, whereas the DCR for nivolumab and pembrolizumab was 65.2% and 48.6%, respectively. In comparison, the ORR and DCR in MM were 30% and 56%, respectively, in the current study.…”

Japanese real‐world study of sequential nivolumab and ipilimumab treament in melanoma

“…The median OS during the entire period of using nivolumab and after switching to ipilimumab was 17.1 months. This result was similar to the median OS of 18.0 months for previously treated melanoma in a Japanese phase II clinical trial . Similarly, OS rate at 18 months was 56.5% for treatment‐naïve melanoma in another Japanese phase II clinical trial …”

“…It can therefore be assumed that there are patient groups who are unlikely to respond to anti‐PD‐1 antibody monotherapy or nivolumab plus ipilimumab. In Japanese phase II clinical trials, ORRs to Nivolumab were 28.6% in previously treated advance melanoma and 34.8% in treatment‐naïve advanced melanoma, and ORR of 10.0% and BOR of 20.0% to ipilimumab were reported …”

Three cases of nivolumab therapy‐failed advanced melanoma successfully controlled by ipilimumab with intensity‐modulated radiotherapy

“…Recently, anti‐programmed death 1 (PD‐1) antibody (Ab) monotherapy has been one of the first‐line therapies for the treatment of advanced melanoma, especially for BRAF mutation‐negative melanoma . However, its efficacy rate is 24.1–34.8% in the Japanese population, which is lower than that of a previous clinical trial in another country (43.7%) .…”