TBP indicates treatment beyond progression

TBP indicates treatment beyond progression. Open in a separate window Figure 3. target lesion reduction of greater than 30% after progression compared with baseline, with no new or unexpected adverse events. Meaning Continued treatment with nivolumab may be 3,4-Dehydro Cilostazol an option to achieve further benefit without compromising safety in some patients with advanced melanoma. Abstract Importance Immune checkpoint inhibitors have exhibited atypical response patterns, which may not be fully captured by conventional response criteria. There is a need to better understand the potential benefit of continued immune checkpoint inhibition beyond progression. Objective To evaluate the safety and potential benefit of nivolumab 3,4-Dehydro Cilostazol (antiCprogrammed cell death receptor 1) monotherapy beyond Response Evaluation Criteria in Solid Tumors (RECIST) v1.1-defined progression. Design, Setting, and Participants Pooled, retrospective analysis of data from phase 3 trials of nivolumab in treatment-naive patients with advanced melanoma (CheckMate 066 or CheckMate 067) conducted at academic and clinical malignancy centers. Participants were patients treated beyond first disease progression, defined as those who received their last dose of nivolumab more than 6 weeks after progression (TBP group); and patients not treated beyond progression, who discontinued nivolumab therapy before or at progression (non-TBP group). Data analyses were conducted from November 6, 2015, to January 11, 2017. Interventions Nivolumab (3 mg/kg every 2 weeks) administered until progression or unacceptable toxic effects. Patients could be treated beyond progression 3,4-Dehydro Cilostazol if deriving apparent clinical benefit and tolerating study drug, at the investigators discretion. Main Outcomes and Steps Tumor response and safety in TBP and non-TBP patients. Results Among 526 randomized patients (39% [n?=?203] female; median age, 62 years [range, 18-90 years]), 306 (58%) experienced disease progression, including 85 (28%) TBP patients and 221 (72%) non-TBP patients. Twenty-four (28%) of the TBP patients had a target lesion reduction of greater than 30% after progression compared with baseline (TBP 30% group). At the time of this analysis, 65 (76%) TBP patients and 21 (87%) TBP 30% patients were still alive; 27 (32%) and 11 (46%), respectively, continued to receive treatment. Median (range) time from progression to last dose of treatment was 4.7 (1.4-25.8) months for TBP patients and 7.6 (2.4-19.4) months for TBP 30% patients. Median (range) time from progression to greater than 30% tumor reduction was 1.4 (0.2-7.0) months. Treatment-related select grade 3 to 4 4 adverse events were similar in the TBP and non-TBP groups (5 [6%] and 9 [4%], respectively). Conclusions and Relevance A substantial proportion of selected patients treated with frontline nivolumab who were clinically stable and judged to be eligible for treatment beyond RECIST v1.1Cdefined progression by the treating investigators derived apparent clinical benefit without compromising safety. Further analysis will help define the potential benefit of continued nivolumab treatment beyond progression. Trial Registration clinicaltrials.gov Identifiers: “type”:”clinical-trial”,”attrs”:”text”:”NCT01721772″,”term_id”:”NCT01721772″NCT01721772 (CheckMate 066) and “type”:”clinical-trial”,”attrs”:”text”:”NCT01844505″,”term_id”:”NCT01844505″NCT01844505 (CheckMate 067) Introduction Immune checkpoint inhibitors, which enhance antitumor immune response, are associated with atypical response patterns that may not be fully captured by conventional response criteria such as Response Evaluation Criteria in Sound Tumors (RECIST). These atypical response patterns include responses following an apparent increase in tumor burden (pseudoprogression) and responses in the presence of 3,4-Dehydro Cilostazol new lesions. In advanced melanoma, immune-related responses have been observed in?approximately?10% of patients treated with ipilimumab (antiCcytotoxic T-lymphocyte antigen 4), and in?approximately?7% to 9% of patients treated with nivolumab or pembrolizumab (antiCprogrammed cell Rabbit Polyclonal to EDG1 death receptor 1 [antiCPD-1]). Nivolumab is usually a fully human monoclonal IgG4 3,4-Dehydro Cilostazol antibody that selectively blocks the conversation between PD-1 on activated T cells and its ligands, programmed cell.