Peripheral blood and tumor biomarkers in patients with advanced melanoma treated with combination nivolumab (anti-PD-1, BMS-936558, ONO-4538) and ipilimumab

Callahan, Margaret K.; Horak, Christine E.; Schaer, David; Yuan, Jianda; Lesokhin, Alexander M.; Kitano, Shigehisa; Qin, Hong; Ariyan, Charlotte E.; Busam, Klaus J.; Feely, William F.; Jure-Kunkel, Maria; Grosso, Joseph F.; Simon, Jason S.; Wigginton, Jon M.; Gupta, Ashok; Phillips, Teresa A.; Simmons, Pauline; Sznol, Mario; Wolchok, Jedd D.

doi:10.1186/2051-1426-1-s1-o6

Cited by 12 publications

(11 citation statements)

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“…At present, no predictive biomarkers have been validated that can be used to guide patient selection for treatment with immunotherapy. Although there are some data to suggest that objective response rates with nivolumab, either as monotherapy or in combination with ipilimumab, are highest in patients with positive PDL1 expression in NSCLC and melanoma, the absence of this marker is not an indication that patients will fail to respond to treatment [85,86]. …”

Section: Introductionmentioning

confidence: 99%

What have we learned from cancer immunotherapy in the last 3 years?

Ascierto

Marincola

2014

Journal of Translational Medicine

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Until recently, most immunotherapeutic approaches used to fight cancer were ineffective, counteracted by the tumour’s ability to evade immune attack. However, extensive research has improved our understanding of tumour immunology and enabled the development of novel treatments that can harness the patient’s immune system and prevent immune escape. Over the last few years, through numerous clinical trials and real-world experience, we have accumulated a large amount of evidence regarding the potential for long-term survival with immunotherapy agents in various types of malignancy. The results of these studies have also highlighted a number of recurring observations with immuno-oncology agents, including their potential for clinical application across a broad patient population and for both conventional and unconventional response patterns. Furthermore, given the numerous immune checkpoints that exist and the multiple mechanisms used by tumours to escape the immune system, targeting distinct checkpoint pathways using combination approaches is an attractive therapeutic strategy with the potential to further enhance the antitumour immune response.

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Section: Introductionmentioning

confidence: 99%

What have we learned from cancer immunotherapy in the last 3 years?

Ascierto

Marincola

2014

Journal of Translational Medicine

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“…In the melanoma trial, 37 responses to combined checkpoint blockade were seen with equal frequency in PD-L1-positive and -negative tumors, suggesting that the addition of anti-CTLA-4 may alter factors in the tumor microenvironment, possibly rendering PD-L1-negative tumors more susceptible to anti-PD-1 blockade. 35 A trial comparing clinical activity of the combination of nivolumab and ipilimumab with standard TKI therapy in advanced RCC has been initiated (ClinicalTrials.gov No. NCT01472081).…”

mentioning

confidence: 99%

Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab

McDermott

Drake

Sznol

et al. 2015

JCO

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Purpose Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts. Patients and Methods A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation. Results Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible. Conclusion Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC.

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“…22 Subsequent data suggested that metastatic melanoma patients who lacked PD-L1 expression their tumor could still respond to PD-1/PD-L1 inhibtion, albeit at a lower rate. 26,27,28 While these results showed the utility of PD-L1 staining, this may not yet be useful at the individual patient level since patients with PD-L1 negative tumors can have responses to treatment. Ongoing clinical trials that have collected pre-treatment tumor biopsies will be useful in future assessment of PD-L1 expression and correlations with tumor response.…”

Section: Future Directionsmentioning

confidence: 94%