Utilization and Safety of Ipilimumab Plus Nivolumab in a Real-World Cohort of Metastatic Renal Cell Carcinoma Patients.

INTRODUCTION: Ipilimumab plus nivolumab was associated with a survival benefit in a phase III clinical trial of first-line treatment for metastatic renal cell carcinoma (mRCC). In this study, mRCC patients from the Canadian Kidney Cancer Information System (CKCis) database who received first-line ipilimumab plus nivolumab were analyzed to determine the safety and outcomes in a real-world setting. PATIENTS AND METHODS: Patients who received ipilimumab plus nivolumab as first-line therapy for mRCC in CKCis, were identified, and the amount of treatment received, discontinuation rates, and reasons for discontinuing treatment were determined. Toxicity data, including type and grade, were collected. Efficacy outcomes of interest included overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). RESULTS: The cohort included 195 patients, the majority with clear cell histology (74%). All 4 cycles of ipilimumab plus nivolumab were administered in 124 patients (64%). Progressive disease (n = 87; 45%) and toxicity (n = 36; 18%) were the most common causes for discontinuing treatment. Several patients (n = 18) did not receive all 4 doses of ipilimumab but received single agent nivolumab. The estimated median OS was 54.5 months (95% CI, 17.7 - NE) and 12-month OS was 72.2% (95% CI, 65.0 - 79.3). Median PFS was 7.4 months (95% CI 5.3 - 10.2) and ORR was 42.5%. Patients who received all 4 cycles of ipilimumab plus nivolumab had better ORR (50% vs. 28%) and a longer PFS and OS than those who received less than 4 cycles (P < .0001). Ninety-five AEs were documented in 72 patients who required dose reduction/change, with colitis being the most frequent. CONCLUSION: In this real-world cohort of treatment-naïve mRCC patients, outcomes, and safety were comparable to previously reported clinical trial data.

Open extremity fractures: impact of delay in operative debridement and irrigation.

BACKGROUND: Early (<8 hours) operative debridement and irrigation (D&I) of open fractures are considered essential to reduce the risk of deep infection. With the advent of powerful antimicrobials, this axiom has been challenged. The current study evaluates the rates of deep infections of open fractures in relation to the time to the first D&I. METHODS: A list of all blunt open fractures during a 6-year period was obtained from the trauma registry. Patients were evaluated for age, Injury Severity Score (ISS), physiologic derangement (systolic blood pressure, lactate, Revised Trauma Score [RTS]), and fracture type (Gustilo). Time to the first D&I was calculated. All patients received appropriate prophylactic antimicrobials. Infection rates were calculated and correlated to the time to the first D&I (<8 hours vs. >8 hours). Regression analysis was performed to identify independent predictors of infection. RESULTS: During the 72-month study period, 404 patients met entry criteria, with 415 open extremity fractures (upper, 129; lower, 287). Early (<8 hours) and delayed (>8 hours) groups were well matched, although the age was lower and ISS was higher in the group with greater than 8 hours. The rates of infection were 35 (11%) of 328 (<8 hour) and 17 (19%) of 87 (>8 hours) (p < 0.05). When fractures were subgrouped by extremity, for the lower extremity, both a delay of greater than 8 hours and higher Gustilo type correlated with the development of infection. In the upper extremity, only higher Gustilo type correlated, and a delay to the first D&I did not increase the incidence of infection. Regression analysis revealed that higher ISS (odd ratio [OR], 1.052; 95% confidence interval [CI], 1.019-1.086), Gustilo grade, and a delay of greater than 8 hours (OR, 2.035; 95% CI, 1.022-4.054) were independent predictors of infection for the all-extremity model. Separate models for upper and lower extremities showed that the same three parameters were independent predictors for the lower extremity (ISS: OR, 1.045; 95% CI, 1.004-1.087; Gustilo type and >8-hour delay: OR, 3.006; 95% CI, 1.280-7.059), but none for the upper extremity. CONCLUSION: Delay of greater than 8 hours to the first D&I for open fractures of the lower extremity increases the likelihood of infection but not for the upper extremity. Higher Gustilo type open fractures have a higher incidence of infection for both upper and lower extremities. The results have important implications in an era of decreasing surgeon availability, especially in off hours. LEVEL OF EVIDENCE: Therapeutic study, level IV.