Real‐world efficacy and safety data of nivolumab and ipilimumab combination therapy in Japanese patients with advanced melanoma

Abstract

The efficacy and safety of nivolumab + ipilimumab combination therapy were retrospectively examined in Japanese patients with unresectable advanced melanoma in clinical practice. Fifty‐seven patients with advanced melanoma received the nivolumab + ipilimumab combination therapy. The primary site was cutaneous, mucosal, uveal and unknown in 35, 16, two and four patients, respectively. The overall response rate was 26.3%, with complete response observed in two (3.5%) patients, partial response in 13 (22.8%), stable disease in 12 (21.1%) and progressive disease in 30 (52.6%). The response rate in the treatment‐naive and prior systemic therapy group was 40.7% and 13.3%, respectively. For those treated with a single immune checkpoint inhibitor followed by the nivolumab + ipilimumab combination therapy as second‐line therapy after disease progression, the response rate was 18.8%. Median progression‐free survival (PFS) and overall survival (OS) in all patients was 3.3 and 14 months, respectively. Median PFS in the treatment‐naive and prior systemic therapy groups was 13 and 2 months, respectively. Median OS was unreached in the treatment‐naive group and was 6.3 months in prior systemic therapy groups. There was no significant difference in PFS and OS for non‐acral, acral and mucosal melanoma. Adverse events occurred in 86% of patients; 56.1% were grade 3 or worse. The response rate in an actual clinical setting, including the prior systemic therapy group, was lower than that in the global study and the Japanese phase II study. However, in the treatment‐naive group, the rate was equivalent to that in the Japanese phase II study. PFS and OS in the treatment‐naive group were comparable with those in the global study and Japanese phase II study, suggesting that the treatment was effective. The proportion of grade 3 and 4 immune‐related adverse events was as high as that in the global study and Japanese phase II study.

Anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy in unresectable or metastatic mucosal melanoma: a retrospective, multicenter study of 329 Japanese cases (JMAC study)

“…Four studies have tested the efficacy of PD1 plus radiotherapy, including a study recently reported by our group, 22 , 23 , 24 , 25 two studies have tested PD1 plus a vascular endothelial growth factor receptor (VEGFR) inhibitor, 26 , 27 and four studies explored the efficacy of PD1 + CTLA4. 6 , 16 , 17 , 28 , 29 …”

“… 28 , 29 A single-institutional retrospective study that included 16 Japanese MCM patients showed an ORR of 12.5% (25% among the 8 patients who received PD1 + CTLA4 as a first-line therapy) and a median PFS of 2.6 months; the median OS was not reached. 6 In a Caucasian population, a pooled analysis of the CheckMate-067 and CheckMate-069 cohorts (35 MCM patients) showed that nivolumab plus ipilimumab displayed more favorable activity than nivolumab monotherapy, with an ORR of 37.1% and a median PFS of 5.9 months, although statistical analysis was not carried out. 16 Shoushtari et al.…”

“… 2 , 3 , 4 Notably, advanced MCM (unresectable primary or metastatic) is the most common advanced-stage subtype in Japan, accounting for 28%-38% of all melanoma subtypes at this stage. 5 , 6 , 7 MCM is genetically, molecularly, and clinically different from NACM in that it has distinct oncogenic drivers with a 3%-15% infrequent rate of BRAF V600 mutation, 8 a lower tumor mutational burden, 9 and a highly aggressive phenotype with a poorer prognosis. 10 …”

Combined carboplatin and paclitaxel therapy improves overall survival in patients with nivolumab‐resistant acral and mucosal melanoma

“…The RR of combined nivolumab and ipilimumab therapy for MCM as the second-line treatment was 0%, whereas it was 20% for cutaneous melanoma. 7 Moreover, the RR of ipilimumab monotherapy after progression on anti-programmed cell death protein 1 antibody monotherapy was reported as only 3Á6%. 8 Our study was limited by its retrospective design and small sample size.…”

“…6 Similar maximum doses (400 mg m -2 ) have been proposed in nodal T-cell lymphomas. 7 We report our experience with PEG-DOXO (Caelyx â ) as a maintenance strategy in advanced-stage MF, describing 18 patients who continued to receive doxorubicin following an initial response. Patient characteristics are shown in Table 1.…”