A Prospective, Real-World, Multinational Study of Naloxegol for Patients with Cancer Pain Diagnosed with Opioid-Induced Constipation—The NACASY Study

Cancer pain; Naloxegol; Ppioid-induced constipationDolor por cáncer; Naloxegol; Estreñimiento inducido por opioidesDolor per càncer; Naloxegol; Restrenyiment induït per opioidesThe Naloxegol Cancer Study (NACASY) was a multinational European study aimed to evaluate the 4-week safety and efficacy of naloxegol in a real-world setting in patients with cancer pain diagnosed with opioid-induced constipation. The primary safety endpoint was the incidence of adverse events leading to study discontinuation. We recruited 170 patients who received at least one dose of naloxegol (i.e., safety population). Out of 170 patients, 20 (11.8%, 95%CI 6.9–16.6) discontinued the study due to adverse events, and, of them, 12 (7.1%, 95%CI 3.2–10.9%) were study discontinuations due to naloxegol-related adverse events. From 76 patients subjects who had completed both 4 weeks of treatment and 28 days of the diary, 55 patients (72.4%, 95% CI 62.3–82.4%) were regarded as responders (i.e., showed ≥3 bowel-movements per week and an increase of ≥1 bowel-movement over baseline) to naloxegol treatment. The Patient Assessment of Constipation—Quality of Life Questionnaire total score and all its subscales improved from baseline to 4 weeks of follow up. Our findings support and provide new evidence about the beneficial effect of naloxegol in terms of improvement of constipation and quality-of-life in patients with cancer-related pain and opioid-induced constipation and show a safety profile consistent with previous pivotal and real-world studies.This project was funded by Kyowa Kirin International. Role of the funding source: The funder of the study and its employees and assignees were involved in study design, data collection, data analysis, data interpretation, and writing of all related reports and publications

PSA Kinetics as Prognostic Markers of Overall Survival in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone Acetate

Background: Abiraterone acetate (AA) is widely used in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). However, a significant percentage of patients will still progress, highlighting the need to identify patients more likely to benefit from AA. Parameters linked to prostate-specific antigen (PSA) kinetics are promising prognostic markers. We have examined clinical and PSA-related factors potentially asso- ciated with overall survival (OS) in patients treated with AA. Methods: Between 2011 and 2014, 104 patients with mCRPC treated with AA after progression to docetaxel at centers of the Catalan Institute of Oncology were included in this retrospective study. Patients were assessed monthly. Baseline characteristics and vari- ables related to PSA kinetics were included in univariate and multivariate analyses of OS. Results: Median OS was 16.4 months (range 12.4-20.6) for all patients. The univariate analysis identified the following baseline characteristics as significantly associated with OS: ECOG PS, location of metastases, time between starting androgen deprivation therapy and starting AA, time between stopping docetaxel treatment and starting AA, neutrophil- lymphocyte ratio (NLR), alkaline phosphatase levels, and PSA levels. Factors related to PSA kinetics associated with longer OS were PSA response >50%, early PSA response (>30% decline at four weeks), PSA decline >50% at week 12, PSA nadir 140 days, the combination of PSA nadir and time to PSA nadir, and low end-of- treatment PSA levels. The multivariate analysis identified ECOG PS (HR 37.46; p<0.001), NLR (HR 3.7; p<0.001), early PSA response (HR 1.22; p=0.002), and time to PSA nadir (HR 0.39; p=0.002) as independent prognostic markers. Conclusion: Our results indicate an association between PSA kinetics, especially early PSA response, and outcome to AA after progression to docetaxel. Taken together with other factors, lack of an early PSA response could identify patients who are unlikely to benefit from AA and who could be closely monitored with a view to offering alternative therapies

Immunotherapy Resumption/Rechallenge in Melanoma Patients after Toxicity: Do We Have Another Chance?

Introduction: Immune checkpoint inhibitors (ICIs) have radically changed the prognosis of several neoplasias, among them metastatic melanoma. In the past decade, some of these new drugs have appeared together with a new toxicity spectrum previously unknown to clinicians, until now. A common situation in daily practice is that a patient experiences toxicity due to this type of drug and we need to resume or rechallenge treatment after resolving the adverse event. Methods: A PubMed literature review was carried out. Results: The published data regarding the resumption or rechallenge of ICI treatment in melanoma patients is scarce and heterogeneous. Depending on the study reviewed, the recurrence incidence of grade 3&ndash;4 immune-related adverse events (irAEs) ranged from 18% to 82%. Conclusion: It is possible to resume or rechallenge, but each patient should be evaluated by a multidisciplinary team for close monitoring and assessment of the risk/benefit ratio before initiating treatment