Retrospective study of advanced melanoma patients treated with ipilimumab after nivolumab: Analysis of 60 Japanese patients

To describe the treatment patterns of nivolumab and ipilimumab in Japan, a retrospective observational study was conducted in melanoma patients who received nivolumab and ipilimumab sequentially. Patients who received nivolumab and ipilimumab in combination were excluded from this study. Efficacy was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) in terms of the overall response rate (ORR), progression‐free survival (PFS), and disease control rate (DCR). Overall survival (OS) was also evaluated. Safety was assessed by the Common Terminology Criteria for Adverse Events (CTCAE). The treatment for all 68 patients enrolled involved switching from nivolumab to ipilimumab in 61 patients and switching from ipilimumab to nivolumab in seven patients. Switching occurred because of progressive disease in 55 patients and adverse events in eight patients. The median number of ipilimumab doses was three. Ipilimumab treatment achieved an ORR and DCR of 4.9% and 21.3%, respectively, and the median OS from start of ipilimumab was 7.0 months. During the study period, no new safety signals were noted. Independent factors which were indicative of poor prognosis for PFS were high neutrophil‐to‐lymphocyte ratio (NLR) and high C‐reactive protein (CRP) levels before ipilimumab treatment. An evaluation over a washout period indicated that no significant relationship existed with efficacy or safety. For the sequential administration of nivolumab and ipilimumab in Japanese melanoma patients, switch from nivolumab to ipilimumab was common, and the major reason for switching was progressive disease. The major prognostic factors for ipilimumab PFS after nivolumab were NLR and CRP before ipilimumab treatment.

Section: Discussionsupporting

confidence: 90%

Section: Discussioncontrasting

confidence: 60%

Section: Discussionmentioning

confidence: 89%

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

Tsutsumida

Fukushima

Yokota

et al. 2019

“…We administrated ipilimumab to patients who showed disease progression while being treated with an anti‐PD‐1 antibody. In past reports, the objective response rates were 3.6–16% in advanced melanoma patients given an anti‐PD‐1 antibody followed by ipilimumab . However, ipilimumab therapy is reportedly used more frequently and produces more severe immune‐related adverse events (irAE) than nivolumab .…”

Section: Introductionmentioning

confidence: 99%

Investigation of clinical factors associated with longer overall survival in advanced melanoma patients treated with sequential ipilimumab

Muto¹,

Kitano

Tsutsumida

et al. 2019

Self Cite

Melanoma is one of the most serious form of skin cancer. Nowadays, ipilimumab is used for advanced melanoma refractory to first‐line anti‐programmed death 1 (PD‐1) antibodies. Thirty patients (male : female ratio, 18:12; median age, 60.5 years) sequentially treated with ipilimumab after anti‐PD‐1 antibody (nivolumab or pembrolizumab), while 58 (male : female ratio, 27:31; median age, 66.5 years) with anti‐PD‐1 antibody only. The kind of therapy and schedules were as follows: nivolumab, 2 mg/kg at 3‐week intervals or at 3 mg/kg every 2 week; pembrolizumab, 2 mg/kg every 3 weeks; ipilimumab, 3 mg/kg at 3‐week intervals for four doses. The sequential therapy was selected for the patients with disease progression and/or recovered from severe (immune‐related [ir]) adverse events (AE) after PD‐1 blockade monotherapy. We evaluated multiple parameters and analyzed their relevance to overall survival (OS). The best objective response rate was 6.7% in sequential ipilimumab treatment. Median OS was 163 days (range, 16–489). Baseline absolute lymphocyte count (ALC) and performance status (PS) before sequential ipilimumab were associated with OS in univariate analyses. Baseline PS and irAE within 6 weeks after ipilimumab administration showed significant differences on multivariate analysis. Prior to first‐line PD‐1 blockade, these parameters were not associated with OS. The other factors (i.e. age, sex, number of doses, absolute neutrophil counts, neutrophil : lymphocyte ratio, lactate dehydrogenase and C‐reactive protein) were not associated with OS. [Correction added on 17 April 2019, after first online publication: ‘not related to OS' has been amended to ‘not associated with OS’.] Ipilimumab as sequential therapy did not appear to improve OS and was associated with more severe irAE than PD‐1 blockade monotherapy. We need to carefully consider treating patients with poor PS and low ALC.

“…For the patients with anti‐PD‐1 Ab‐failed advanced melanoma, ipilimumab is another choice, especially for melanoma without the BRAF gene mutation . However, because the efficacy of ipilimumab in patients with nivolumab‐resistant melanoma is extremely low after objective tumor progression, radiotherapy is sometimes administrated in combination with ipilimumab . Interestingly, Chandra et al .…”

Section: Discussionmentioning

confidence: 99%

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

Amagai

Fujimura

Kambayashi

et al. 2019

Self Cite

Anti‐programmed death 1 antibody monotherapy is a first‐line and widely used immunotherapy for the treatment of advanced melanoma. However, its efficacy rate is lower in the Japanese population compared with the Caucasian population. Ipilimumab is another immune checkpoint inhibitor (ICI) that activates and increases T cells, which suppress the function of regulatory T cells. Previous reports have suggested that ipilimumab is useful for treating advanced melanoma, particularly in combination with radiation therapy. In this report, we described three cases of nivolumab‐resistant melanoma successfully controlled by ipilimumab with intensity‐modulated radiotherapy, which may enhance the therapeutic effects of the sequential administration of ICI.