Effectiveness Of Nivolumab In Patients Research Articles

Effectiveness and safety of nivolumab in patients with advanced melanoma: A multicenter, observational study

This retrospective observational study aimed to determine the effectiveness, safety and patterns of the use of nivolumab in patients with advanced melanoma in real-world clinical practice in France using data from a Temporary Authorization for Use Program (ATU). Data were collected from patients with unresectable or metastatic melanoma enrolled in a French national database (Réseau pour la Recherche et l'Investigation Clinique sur le Mélanome: Ric-Mel) and treated with nivolumab during the ATU program (12 September 2014 to 31 August 2015). The primary objectives of the study were to evaluate the effect of patient characteristics on clinical response and overall survival (OS). Among 400 included patients (median age 66 years), the majority (83%) received nivolumab as second- or subsequent-line therapy. The median durations of progression-free survival and OS were 3.3 and 14.1 months, respectively, and 31.6% of patients achieved an objective response with a median duration of 20.1 months (range: 0-34.7). The safety profile of nivolumab was manageable and consistent with those of previous clinical trials, with an incidence of grade 3-5 adverse events of 13.8%. The safety and effectiveness of nivolumab in patients with advanced melanoma in real-world clinical practice in France were in line with the data reported in the Phase 3 trials CheckMate 066 and 037 of nivolumab in this patient population.

Cost Effectiveness of Nivolumab in Patients with Advanced, Previously Treated Squamous and Non-squamous Non-small-cell Lung Cancer in England.

ObjectiveThe aim of this study was to investigate the cost effectiveness of nivolumab versus docetaxel in previously treated, advanced non–small-cell lung cancer (NSCLC) in England and assess how conditional reimbursement within the Cancer Drugs Fund (CDF) can be used to ensure timely patient access to effective treatments.MethodsCost-effectiveness models developed for the National Institute for Health and Care Excellence (NICE) TA483 (squamous) and TA484 (non-squamous) technology appraisals were supplemented with updated overall survival (OS), progression-free survival (PFS), and time-to-treatment discontinuation data collected as part of the CDF data collection agreement. Both models were developed by using a partitioned-survival approach based on PFS and OS predictions from CheckMate 017 and CheckMate 057 to estimate the projected proportion of patients in each health state (progression free, progression, death) throughout the model’s time horizon. The primary outcomes were estimated costs, quality-adjusted life-years (QALYs), and the resulting incremental cost-effectiveness ratio (ICER) expressed as cost/QALY gained.ResultsBase-case ICERs for treating patients with nivolumab versus docetaxel were £35,657/QALY and £38,703/QALY for squamous and non-squamous NSCLC patients, respectively, which are substantially lower than those obtained from what were deemed to be the most appropriate analyses for decision making in the original submissions when run with the same patient access scheme discount: £68,576/QALY and £73,189/QALY gained for squamous and non-squamous NSCLC, respectively.ConclusionsNivolumab versus docetaxel is cost effective for treating locally advanced/metastatic NSCLC after prior chemotherapy in adults, regardless of tumour histology or programmed death-ligand 1 expression status.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-020-00245-4.

The neutrophil-lymphocyte ratio has a role in predicting the effectiveness of nivolumab in Japanese patients with metastatic renal cell carcinoma: a multi-institutional retrospective study

BackgroundThe neutrophil-lymphocyte ratio (NLR) is a well-known prognostic marker in various cancers. However, its role as a predictive marker for the effectiveness of nivolumab in patients with metastatic RCC (mRCC) remains unclear. We evaluated the relationships between the NLR and progression-free survival (PFS) or overall survival (OS) in mRCC patients treated with nivolumab.MethodsThe data of 52 mRCC patients who received nivolumab therapy were collected from seven institutes and evaluated. The median follow-up period from treatment with nivolumab was 25.2 months (IQR 15.5–33.2).ResultsThe median duration of nivolumab therapy was 7.1 months (IQR 2.9–24.4). The objective response rate was 25% and the 1- and 2-year PFS rates were 46.2 and 25.2%, respectively. The median NLR values at baseline and 4 weeks were 3.7 (IQR 2.7–5.1) and 3.3 (IQR 2.4–5.7), respectively. In the multivariate analysis, an NLR of ≥3 at 4 weeks was an independent predictor of PFS (P = 0.013) and OS (P = 0.034). The 1-year PFS of patients with an NLR of < 3 at 4 weeks was better than that of those with an NLR of ≥3 (75% versus 29%, P = 0.011). The 1-year OS of patients with an NLR of < 3 at 4 weeks was also better than that of those with an NLR of ≥3 (95% versus 71%, P = 0.020).ConclusionsAlthough the baseline NLR was not associated with PFS or OS, an NLR of ≥3 at 4 weeks after the initiation of therapy might be a robust predictor of poor PFS and OS in mRCC patients undergoing sequential treatment with nivolumab.

Real-world effectiveness of nivolumab in patients with non-small-cell lung cancer: a systematic review and meta-analysis.

Background: The effectiveness of immunotherapies for non-small-cell lung cancer under real-world clinical settings remains uncertain. Materials & methods: Systematic searches of PubMed, EMBASE and Web of Science were conducted. Random-effects models were used to estimate pooled median overall survival and progression-free survival estimates. Results: 36 studies of nivolumab were included for narrative synthesis and 11 of these studies were included for meta-analysis. Age, sex, histology and prior lines of treatment did not affect survival outcomes, while Eastern Cooperative Oncology Group Performance Status and brain metastasis were inversely associated with survival. In the meta-analysis, nivolumab was associated with 9.6 months (95% CI: 8.4-10.9) of overall survival and 2.6 months (95% CI: 1.6-3.6) of progression-free survival. Conclusion: Very-low-certainty evidence suggested the real-world effectiveness of nivolumab was consistent with those observed in the clinical trials.

464 Serum level of tumor-associated macrophage (TAMs)-related factors may be a predictive marker of the effectiveness of nivolumab in patients with advanced cutaneous melanoma

Antibodies against PD1, such as nivolumab and pembrolizumab, are widely used for treating various cancers, including advanced melanoma. PD1 antibody-based immunotherapy, co-administration of nivolumab and ipilimumab, is one of the optimal immunotherapies, especially in advanced melanoma with a high tumor mutation burden. Since this combined therapy leads to a high frequency of serious immune-related adverse events (irAEs) in patients with advanced melanoma, biomarkers are needed to evaluate the nivolumab efficacy to avoid serious irAEs caused by ipilimumab. Notably, PD-1 expression is a key factor in maintaining CD163+TAMs as M2-polarized, and blockade of PD-1/PD-L1 leads to conversion of TAMs into M1-polarized activated macrophages, leading to the release of sCD163 and other TAMs related chemokines (e.g. CXCL5, CXCL10, CCL22) in serum. From the above findings, in this study we analyzed the serum levels of sCD163 as well as CXCL5, CXCL10 and CCL22 in 75 cases of advanced melanoma using anti-PD1 antibodies. The serum levels of sCD163 were significantly increased after 6 weeks in responders compared to non-responders after the initial administration of nivolumab for cutaneous melanoma. Moreover, high baseline serum levels of CXCL5 correlated with the objective response to nivolumab in patients with advanced melanoma, whereas there were no significant relationships between the serum levels of CXCL10 and CCL22. These results suggest that sCD163 in combination with CXCL5 may be useful as a biomarker for selecting patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy.

Serum Level of Soluble CD163 May Be a Predictive Marker of the Effectiveness of Nivolumab in Patients With Advanced Cutaneous Melanoma.

Antibodies against programmed cell death protein 1, such as nivolumab and pembrolizumab, are widely used for treating various cancers, including advanced melanoma. Nivolumab significantly prolongs survival in patients with metastatic melanoma, and sequential administration with lipilimumab may improve outcomes when switched at the appropriate time. Biomarkers are therefore needed to evaluate nivolumab efficacy soon after first administration. This study analyzed serum levels of soluble cluster of differentiation 163 (sCD163) in 59 cases of advanced cutaneous melanoma and 16 cases of advanced mucosal melanoma treated using nivolumab. Serum levels of sCD163 were significantly increased after 6 weeks in responders compared to non-responders after initial administration of nivolumab for cutaneous melanoma. In contrast, no significant difference between responders and non-responders was seen among patients with non-cutaneous melanoma. These results suggest that sCD163 may be useful as a biomarker for selecting patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy.