Efficacy and safety of retreatment with nivolumab in metastatic melanoma patients previously treated with nivolumab

Nomura, Motoo; Otsuka, Atsushi; Kondo, Tomohiro; Nagai, Hiroki; Nonomura, Yumi; Kaku, Yo; Matsumoto, Shigemi; Muto, Manabu

doi:10.1007/s00280-017-3444-0

Cited by 55 publications

(55 citation statements)

References 20 publications

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“…A previous report suggests that the response to initial ICI treatments correlates with the clinical response to ICI rechallenge treatment in patients with melanoma [30]. However, our results failed to indicate a relationship between clinical outcomes of initial ICI treatment and ICI rechallenge treatment in patients with NSCLC.…”

Section: Discussioncontrasting

confidence: 99%

Retrospective Efficacy Analysis of Immune Checkpoint Inhibitor Rechallenge in Patients with Non-Small Cell Lung Cancer

Katayama

Shimamoto

Yamada

et al. 2019

JCM

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Little is known regarding the effectiveness and tolerability of immune checkpoint inhibitor (ICI) rechallenge after disease progression following initial ICI treatments. To identify eligible patients for ICI rechallenge, we retrospectively analyzed the relationship between clinical profiles and the effect of ICI rechallenge in patients with non-small cell lung cancer (NSCLC). We enrolled 35 NSCLC patients at six different institutions who were retreated with ICIs after discontinued initial ICI treatments due to disease progression. Cox proportional hazards models were used to assess the impact of clinical profiles on overall survival (OS) and progression-free survival (PFS). Median PFS and OS were 81 d (95% confidence interval, CI, 41–112 d) and 225 d (95% CI 106–361 d), respectively. The objective response rate was 2.9%, and the disease control rate was 42.9%. Multivariate analysis demonstrated that Eastern Cooperative Oncology Group Performance Score (ECOG-PS) ≥ 2 (hazard ratio, HR, 2.38; 95% CI 1.03–5.52; p = 0.043) and body mass index (BMI) > 20 (HR 0.43, 95% CI 0.19–0.95, p = 0.036) were significantly associated with PFS of ICI rechallenge. Our observations suggest that poor ECOG-PS and low BMI at intervention with ICI rechallenge may be negative predictors for ICI rechallenge treatment in patients with NSCLC.

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Section: Discussioncontrasting

confidence: 99%

Retrospective Efficacy Analysis of Immune Checkpoint Inhibitor Rechallenge in Patients with Non-Small Cell Lung Cancer

Katayama

Shimamoto

Yamada

et al. 2019

JCM

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“…Interestingly, in one of the PR patients, the metastases were decreased with nivolumab re-administration. Although the underlying mechanism is not clear, Nomura et al 20 reported that two melanoma patients with PD on both the first-line nivolumab and second-line ipilimumab achieved PR in the third-line nivolumab retreatment. In some sequential cases, the immune status may be altered in response to ipilimumab treatment.…”

Section: Discussionmentioning

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

The Journal of Dermatology

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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.

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“…(nivolumab) and anti-CTLA-4 (ipilimumab) has shown positive results in tumor treatment and significant enhancement in patients with metastatic melanoma [36], advanced RCC [37], and metastatic CRC [16,38] [40]. Based on conditional survival analysis of first-line treatment, Shao [41] showed that patients with advanced RCC put on nivolumab plus ipilimumab therapy had high survival rate compared with sunitinib.…”

Section: Discussionmentioning

confidence: 99%

The efficacy and safety of combined immune checkpoint inhibitors (nivolumab plus ipilimumab): a systematic review and meta-analysis

et al. 2020

Preprint

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Background: Currently, nivolumab and ipilimumab are the most widely used immune checkpoint inhibitors. We performed a meta-analysis to evaluate the efficacy and treatment-related adverse events (TRAEs) of nivolumab-ipilimumab combination therapy in cancer treatment. Methods: We examined data from PubMed, Web of science, EBSCO and Cochrane library. Eleven articles fulfilled our criteria, which we divided into 3 groups; nivolumab and ipilimumab versus ipilimumab, nivolumab and ipilimumab versus ipilimumab and nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3) versus nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1). We measured the complete response (CR), partial response (PR), objective response rate (ORR) and TRAEs in any grade and grade 3 or higher. Results: Compared with ipilimumab alone, the combined immunotherapy had better CR (RR: 4.89, p <0.001), PR (RR: 2.75, p <0.001), and ORR (RR: 3.31, p <0.001). The overall effect estimate favored the combined immunotherapy group in terms of the ORR (RR: 1.40, p <0.001) and PR (RR: 1.50, p <0.001) than nivolumab alone. Finally, N1I3 showed better PR (RR: 1.35, p =0.006) and ORR (RR: 1.21, p =0.03) than N3I1. The incidence of any TRAEs was similar between the both groups (RR: 1.05, p =0.06). However, the incidence of serious adverse events (grade 3 or higher) were lower in group N3I1 than group N1I3 (RR: 1.51, p <0.001). Conclusion: This meta-analysis showed that the curative effect of nivolumab plus ipilimumab was better than that of ipilimumab or nivolumab monotherapy. In the combination group, N1I3 combination was more effective than N3I1. Although the side effects were slightly increased in group N1I3, the overall safety was acceptable.

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Efficacy and safety of retreatment with nivolumab in metastatic melanoma patients previously treated with nivolumab

Abstract: This study showed that retreatment with nivolumab is an option for select metastatic melanoma patients after previous nivolumab treatment.

Cited by 55 publications

References 20 publications

Retrospective Efficacy Analysis of Immune Checkpoint Inhibitor Rechallenge in Patients with Non-Small Cell Lung Cancer

Retrospective Efficacy Analysis of Immune Checkpoint Inhibitor Rechallenge in Patients with Non-Small Cell Lung Cancer

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

The efficacy and safety of combined immune checkpoint inhibitors (nivolumab plus ipilimumab): a systematic review and meta-analysis

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