Nivolumab in Advanced Hepatocellular Carcinoma: Safety Profile and Select Treatment-Related Adverse Events From the CheckMate 040 Study.

BACKGROUND: CheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment-related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open-label CheckMate 040 study. MATERIALS AND METHODS: Select TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose-escalation and -expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and the outcome of treatment with immune-modulating medication (IMM) was evaluated. RESULTS: The analysis included 262 patients. The most common sTRAE was skin (35.5%), followed by gastrointestinal (14.5%) and hepatic (14.1%) events; the majority were grade 1/2, with 10.7% of patients experiencing grade 3/4 events. One patient had grade 5 pneumonitis. Median (range) TTO ranged from 3.6 (0.1-59.9) weeks for skin sTRAEs to 47.6 (47.1-48.0) weeks for renal sTRAEs. Overall, 68% of sTRAEs resolved, with median (range) TTR ranging from 3.7 (0.1-123.3+) weeks for gastrointestinal sTRAEs to 28.4 (0.1-79.1) weeks for endocrine sTRAEs. Most gastrointestinal and all hepatic events resolved with treatment in accordance with established toxicity management algorithms. In 57 patients (40%), sTRAEs were managed with IMM. Reoccurrence of sTRAEs was uncommon following rechallenge with nivolumab. CONCLUSION: Nivolumab demonstrated a manageable safety profile in this analysis of patients with advanced HCC. A majority of sTRAEs resolved with treatment. IMPLICATIONS FOR PRACTICE: Nivolumab is a viable treatment option for patients with previously treated advanced hepatocellular carcinoma as it has demonstrated durable tumor responses and promising survival. Nivolumab has a manageable safety profile. The most common select treatment-related adverse events (sTRAEs) in this analysis were skin related (35%). Gastrointestinal and hepatic sTRAEs were observed in approximately 14% of patients. The majority of sTRAEs resolved (68%). Safety events are easier to manage if addressed early. Patient education on signs and symptoms to watch out for and the importance of early reporting and consultation should be emphasized.

A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma.

BACKGROUND: Preclinical studies have shown synergy between radiation therapy and immunotherapy. However, in almost all preclinical models, radiation is delivered in single doses or short courses of high doses (hypofractionated radiation). By contrast in most clinical settings, radiation is delivered as standard small daily fractions of 1.8-2 Gy to achieve total doses of 50-54 Gy (fractionated radiation). We do not yet know the optimal dose and scheduling of radiation for combination with chemotherapy and immunotherapy. METHODS: To address this, we analyzed the effect of neoadjuvant standard fractionated and hypofractionated chemoradiation on immune cells in patients with locally advanced and borderline resectable pancreatic adenocarcinoma. RESULTS: We found that standard fractionated chemoradiation resulted in a significant and extended loss of lymphocytes that was not explained by a lack of homeostatic cytokines or response to cytokines. By contrast, treatment with hypofractionated radiation therapy avoided the loss of lymphocytes associated with conventional fractionation. CONCLUSION: Hypofractionated neoadjuvant chemoradiation is associated with reduced systemic loss of T cells. TRIAL REGISTRATION: ClinicalTrials.gov NCT01342224, April 21, 2011; NCT01903083, July 2, 2013.

Comparison of local reactions to oxaliplatin infusions by peripheral versus central venous administration.

PURPOSE: Oxaliplatin, a platinum-type alkylator, is not classified as a vesicant but can cause local reactions when infused by peripheral vein. Providence Cancer Center, like other institutions, deferred the venous administration method to clinical judgment incorporating patient preference. Patient experience was evaluated for oxaliplatin-related local reactions by peripheral or central venous administration. METHODS: A retrospective review of the electronic medical record was performed of the period of January 2011 to March 2013 to identify patients who received oxaliplatin. Included were 59 patients who were given the option of either peripheral or central venous drug administration. The two patient groups (peripheral vein vs. central vein administration) were compared in terms of frequency and type of local reactions (redness/discoloration, swelling, numbness/cold, or pain/discomfort). RESULTS: Nineteen (63.3%) of the patients in the peripheral vein group experienced some type of local reaction compared to none in the central vein group (p < .0001). Pain was the most common local reaction, occurring in 17 (56.7%) patients in the peripheral group. Despite the occurrence of a local reaction, the majority of patients did not alter their initial choice of infusion method. CONCLUSION: This is the first published report to characterize and quantify a single institution's experience with oxaliplatin-related local reactions. A significantly greater number of local reactions, particularly pain, occurred with the administration of oxaliplatin peripherally vs. centrally. This analysis impacted our institution's best practice for oxaliplatin infusions.