Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL).

Sznol, Mario; Kluger, Harriet M.; Callahan, Margaret K.; Postow, Michael A.; Gordon, Ruth Ann; Segal, Neil H.; Rizvi, Naiyer A.; Lesokhin, Alexander M.; Atkins, Michael B.; Kirkwood, John M.; Burke, Matthew M.; Ralabate, Amanda; Rivera, A.L.; Kronenberg, Stephanie Anne; Agunwamba, Blessing; Feely, William F.; Qin, Hong; Krishnan, Suba; Gupta, Ashok; Wolchok, Jedd D.

doi:10.1200/jco.2014.32.15_suppl.lba9003

Cited by 93 publications

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“…Overall, the characteristics of response observed with nivolumab plus ipilimumab in the current study are consistent with previously reported results, 15, 16 with most responses occurring by time of first tumor assessment, and in many patients, responses continuing despite discontinuation of therapy. The response rate of the combination regimen in this current phase 2 study was even higher than response rates previously reported, which may be explained by the patient population being treatment naïve in this study.…”

Section: Discussionsupporting

confidence: 92%

“…A prior phase 1 trial of the combination regimen at varying doses showed high 1- (85%) and 2-year (79%) overall survival. 15, 16 …”

Section: Discussionmentioning

confidence: 99%

“…16 PD-L1 positivity was defined as at least 5% of tumor cells exhibiting cell-surface PD-L1 staining of any intensity in a section containing at least 100 evaluable tumor cells.…”

Section: Methodsmentioning

confidence: 99%

“…13, 14 High response rates, prolonged duration of response, and favorable overall survival of 79% at 2 years were seen in a phase 1 study in patients receiving the combination regimen of nivolumab and ipilimumab. 15, 16 Here, we report the results of a randomized, double-blind trial comparing the objective response rate of nivolumab in combination with ipilimumab to standard of care ipilimumab monotherapy as a first line treatment in patients with advanced melanoma.…”

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confidence: 99%

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Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma

et al. 2015

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Background In a phase 1 dose-escalation study, combined inhibition of T-cell checkpoint pathways by nivolumab and ipilimumab demonstrated a high objective response rate, including complete responses in patients with advanced melanoma. Methods In this double-blind study, 142 treatment-naïve patients with metastatic melanoma were randomized 2:1 to receive ipilimumab 3 mg/kg combined with either nivolumab 1 mg/kg or placebo every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg or placebo every 2 weeks until disease progression. The primary endpoint was investigator-assessed objective response in BRAF wild-type patients. Results Among BRAF wild-type patients, the confirmed objective response rate was 61.1% (44/72) in the nivolumab and ipilimumab combination group versus 10.8% (4/37) in the ipilimumab monotherapy group (P<0.001), with complete responses reported in 16 (22.2%) patients in the combination group; none in the ipilimumab group. Median duration of response was not reached with either treatment. Median progression-free survival was not reached for the combination versus 4.4 months for ipilimumab monotherapy (hazard ratio 0.40, 95% CI 0.23 to 0.68; P<0.001). Similar results for response and progression-free survival were also observed in 33 BRAF mutation-positive patients. Grade 3–4 drug-related adverse events were reported in 54.3% of patients receiving the combination compared with 23.9% with ipilimumab monotherapy. Select adverse events of immunological etiology were consistent with phase 1 reports, and most resolved with immune-modulating medication. Conclusion Nivolumab combined with ipilimumab significantly improved objective response rate and progression-free survival compared with ipilimumab monotherapy in treatment-naïve patients with advanced melanoma, and had a manageable safety profile. (ClinicalTrials.gov number, NCT01927419)

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Section: Discussionsupporting

confidence: 92%

“…A prior phase 1 trial of the combination regimen at varying doses showed high 1- (85%) and 2-year (79%) overall survival. 15, 16 …”

Section: Discussionmentioning

confidence: 99%

“…16 PD-L1 positivity was defined as at least 5% of tumor cells exhibiting cell-surface PD-L1 staining of any intensity in a section containing at least 100 evaluable tumor cells.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma

et al. 2015

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“…Importantly, the majority of responses seen in the concurrent arm were fast, deep (one-third achieving 80% reduction in tumour burden) and durable (78% of patients alive at 2 years). 47 Notably, there were some substantial toxicities. In the concurrent regimen, treatment-related grade 3-4 elevated liver enzymes were seen in 15%, gastrointestinal toxicities reported in 9%, rash in 4%, and pneumonitis and endocrinopathy occurred in 2% each.…”

Section: Combinations Of Coinhibitory Checkpoints Targeting Cytotoxicmentioning

confidence: 99%

The promise of immunotherapy in head and neck squamous cell carcinoma: combinatorial immunotherapy approaches

Economopoulou¹,

Kotsantis²,

Psyrri³

2016

ESMO Open

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The immune system plays a fundamental role in preventing cancer development by recognising and eliminating tumour cells. The recent success in the field of immunotherapy has confirmed the potential to exploit the immune response as a cancer treatment. Head and neck squamous cell carcinoma (HNSCC) is a malignancy characterized by dismal prognosis and high mortality rate; low survival outcomes in combination with significant toxicity of current treatment strategies highlight the necessity for novel therapeutic modalities. HNSCC is a favourable disease for immunotherapy, as immune escape plays a key role in tumour initiation and progression. T-cell checkpoint inhibitors targeting programmed cell death protein-1 have emerged as novel immunotherapy agents showing remarkable efficacy in HNSCC. However, only a minority of patients derive benefit for single-agent immunotherapies. In this regard, combinatorial immunotherapy approaches represent an alternative strategy that might increase the number of patients who respond to immunotherapy. Focusing on HNSCC, this review will summarise novel combinations of immune checkpoint blockade with other immunotherapy treatment modalities.

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Targeting immune checkpoints in unresectable metastatic cutaneous melanoma: a systematic review and meta‐analysis of anti‐CTLA‐4 and anti‐PD‐1 agents trials

et al. 2016

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Anti‐cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4) and anti‐programmed cell death‐1 (PD‐1) inhibitors have been shown to significantly improve survival in patients with metastatic cutaneous melanoma. However, there was some heterogeneity as well as some variation in the degree of benefit across studies. We reviewed randomized trials and performed a meta‐analysis to determine the efficacy and safety of immune checkpoint inhibitors in comparison with conventional regimens. Eligible studies were limited to randomized controlled trials comparing anti‐CTLA‐4 or anti‐PD‐1 inhibitors to chemotherapy or vaccination treatment in adult patients with unresectable cutaneous metastatic melanoma. Progression‐free survival (PFS) rate at 6 months was 28.5% versus 17.7% (RR: 0.84, 95% CI: 0.76–0.93), overall survival (OS) rate at 1 year was 51.2% versus 38.8% (RR: 0.72, 95% CI: 0.59–0.88), and overall response rate (ORR) at 6 months was 29.6% versus 17.7% (RR: 0.85, 95% CI: 0.76–0.95) favoring immune check point inhibitors over chemotherapies or vaccination. Immune check point inhibitors were associated with more frequent immune‐related adverse events at 13.7% versus 2.4% of treated patients (RR: 6.74, 95% CI: 4.65–9.75). Subgroup analyses demonstrated significant PFS (RR: 0.92 vs. 0.74, P < 0.00001) and ORR (RR: 0.95 vs. 0.76, P = 0.0004) improvement with anti‐PD‐1 treatment compared to anti‐CTLA‐4 when each of them was compared to control treatments. Collectively, these results demonstrate that immune checkpoint inhibitors have superior outcomes compared to conventional chemotherapies or vaccination, and support the results of recent randomized trials that showed superior outcomes with anti‐PD‐1 agents over ipilimumab in unresectable metastatic cutaneous melanoma patients.

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Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL).

Cited by 93 publications

References 0 publications

Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma

Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma

The promise of immunotherapy in head and neck squamous cell carcinoma: combinatorial immunotherapy approaches

Targeting immune checkpoints in unresectable metastatic cutaneous melanoma: a systematic review and meta‐analysis of anti‐CTLA‐4 and anti‐PD‐1 agents trials

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