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

Abstract

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.

The Prognostic Significance of Baseline Neutrophil-to-Lymphocyte Ratio in Melanoma Patients Receiving Immunotherapy

“…Finally, 18 studies including 2054 patients were included in the meta-analysis. [27][28][29][30][31][38][39][40][41][42][43][44][45][46][47][48][49][50] The main characteristics of the included studies were summarized in Table 1. All the studies were published between 2015 and 2020, with 5 studies published before 2018.…”

Prognostic value of neutrophil-lymphocyte ratio and lactate dehydrogenase in melanoma patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis

“…Eventually selected were 13 studies [23,24,26–36] involving 2328 individuals and concerning NLR, and 42 articles [24–26,30–32,34,36–69] including 5907 patients with regard to LDH. Seven studies [24,26,30–32,34,36] reported both NLR and LDH associated with OS or PFS. As the study by Wagner et al [62] included 2 cohorts, in which patients were treated with different regimens and reported the HR and 95% CI, respectively, we termed them as “ Wagner 2018 cohort 1” and “ Wagner 2018 cohort 2.” The characteristics of the selected studies are summarized in Tables 1 and 2.…”

“…Country Agent Sample size NLR cutoff Survival analysis Analysis model NOS Ascierto 2019 [24] United States Nivolumab\Pembrolizumab 71 5 OS/PFS Multivariate 7 Bartlett 2020 [23] United States Pembrolizumab 224 5 OS Multivariate 7 Balatoni 2018 [27] Hungary Ipilimumab 47 4 OS Univariate 6 Capone2018 [28] Italy Nivolumab 97 5 OS/PFS Multivariate 7 Cassidy 2017 [29] United States Ipilimumab 197 5 OS/PFS Multivariate 8 Chasseuil 2018 [30] France Nivolumab 87 3 OS/PFS Multivariate 7 Ferrucci 2016 [31] Italy Ipilimumab 720 [35] United States Nivolumab plus Ipilimumab 209 4.73 OS Multivariate 7 Tsutsumida 2019 [26] Japan PD-1/PD-L1 + CTLA-4 68 4 OS Multivariate 7 Zaragoza 2016 [36] France Ipilimumab 58 4 OS Multivariate 7…”

Neoadjuvant therapy for melanoma: A critical appraisal

“…Interestingly, the neutrophil to lymphocyte ratio appears to correlate with overall immune status and predicts the likelihood of response, with a high N/L ratio associated with a lower likelihood of benefit 23,24 . Other general markers of the immune state such as C‐reactive protein, a marker of inflammation, have demonstrated some value in assessing responsiveness 25 …”