PURPOSE Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) is approved for first-line treatment of patients with advanced melanoma in several countries. We conducted a phase IIIb/IV study (CheckMate 511) to determine if nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) improves the safety profile of the combination. PATIENTS AND METHODS Patients (N = 360) age 18 years or older with previously untreated, unresectable stage III or IV melanoma were randomly assigned 1:1 to NIVO3+IPI1 or NIVO1+IPI3 once every 3 weeks for four doses. After 6 weeks, all patients received NIVO 480 mg once every 4 weeks until disease progression or unacceptable toxicity. The primary end point was a comparison of the incidence of treatment-related grade 3 to 5 adverse events (AEs) between groups. Secondary end points included descriptive analyses of objective response rate, progression-free survival, and overall survival. The study was not designed to formally demonstrate noninferiority of NIVO3+IPI1 to NIVO1+IPI3 for efficacy end points. RESULTS At a minimum follow-up of 12 months, incidence of treatment-related grade 3 to 5 AEs was 34% with NIVO3+IPI1 versus 48% with NIVO1+IPI3 ( P = .006). In descriptive analyses, objective response rate was 45.6% in the NIVO3+IPI1 group and 50.6% in the NIVO1+IPI3 group, with complete responses in 15.0% and 13.5% of patients, respectively. Median progression-free survival was 9.9 months in the NIVO3+IPI1 group and 8.9 months in the NIVO1+IPI3 group. Median overall survival was not reached in either group. CONCLUSION The CheckMate 511 study met its primary end point, demonstrating a significantly lower incidence of treatment-related grade 3-5 AEs with NIVO3+IPI1 versus NIVO1+IPI3. Descriptive analyses showed that there were no meaningful differences between the groups for any efficacy end point, although longer follow up may help to better characterize efficacy outcomes.

Objective Optimism and social support serve as protective factors against distress in medically ill patients. Very few studies have specifically explored the ways in which these variables interact to impact quality of life (QOL), particularly among patients with advanced cancer. The present study examined the role of optimism as a moderator of the relationship between social support and anxiety, depression, hopelessness, and QOL among patients with advanced cancer. Methods Participants (N = 168) completed self-report assessments of psychosocial, spiritual, and physical well-being, including social support, optimism, hopelessness, depressive and anxious symptoms, and QOL. Hierarchical multiple regression analyses were conducted to determine the extent to which social support and optimism were associated with depressive and anxious symptomatology, hopelessness and QOL, and the potential role of optimism as a moderator of the relationship between social support and these variables. Results Higher levels of optimism were significantly associated with fewer anxious and depressive symptoms, less hopelessness and better QOL. Higher levels of perceived social support were also significantly associated with better QOL. Additionally, optimism moderated the relationship between social support and anxiety, such that there was a strong negative association between social support and anxiety for participants with low optimism. Conclusions This study highlights the importance of optimism and social support in the QOL of patients with advanced cancer. As such, interventions that attend to patients’ expectations for positive experiences and the expansion of social support should be the focus of future clinical and research endeavors.

Objective Cancer patients are advised to quit smoking to reduce treatment complications and future cancer risk. This study's main objective was to evaluate the efficacy of a novel, pre-surgical cessation intervention in newly diagnosed cancer patients scheduled for surgical hospitalization. Methods We conducted a parallel-arm, randomized controlled trial comparing the efficacy of our hospital-based, tobacco cessation “best practices” treatment model (BP; cessation counseling and nicotine replacement therapy) with BP enhanced by a behavioral tapering regimen (scheduled reduced smoking; BP+SRS) administered by a handheld computer before hospitalization for surgery. Cessation outcomes were short (hospital admission and three months) and longer-term (6 months) biochemically-verified smoking abstinence. We hypothesized that BP+SRS would be superior to BP alone. One hundred eighty-five smokers were enrolled. Results Overall, 7-day-point prevalence, confirmed abstinence rates at six months for BP alone (32%) and BP+SRS (32%) were high; however, no main effect of treatment was observed. Patients who were older and diagnosed with lung cancer were more likely to quit smoking. Conclusions Compared to best practices for treating tobacco dependence, a pre-surgical, scheduled reduced smoking intervention did not improve abstinence rates among newly diagnosed cancer patients.

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