Preexisting Autoantibodies and Immune Related Adverse Events in Metastatic Urothelial Carcinoma Patients Treated by Pembrolizumab.

INTRODUCTION: Immune checkpoint inhibitor are standard therapy in metastatic urothelial carcinoma. No predictive biomarker of immune related adverse events (iRAE) exists. Antinuclear antibodies (ANA) can be the sign of a subclinical autoimmune condition that could be enhanced by Immune checkpoint inhibitor. We decided to assess the predictive value of baseline autoantibodies and ANA for iRAE in metastatic urothelial carcinoma patients treated with pembrolizumab and explore their prognostic signification. PATIENTS AND METHOD: Data concerning patients treated in our institution between 2015 and 2020 with pembrolizumab for metastatic urothelial carcinoma with available baseline value of ANA and other autoantibodies was collected. ANA with titer >1/80 were defined positive. RESULTS: A total of 68 patients were included. Fifty-five (80%) had ANA >1/80 and among them 21 patients (30%) had ANA >1/160. Seven patients with ANA >160 (33%) presented iRAE vs. 5 patients (10%) in the rest of the population. Presence of ANA >160 was significantly associated with iRAE (P = .029) and limiting toxicity (P = .048) in univariate analysis. iRAE tend to occur earlier, before the third cycle, for patients with ANA >1/160 as compared to rest of the patients (28% vs. 6%, P = .052). Exploratory analysis did not reveal correlation between progression free survival or overall survival and ANA >1/160 in univariate or in multivariate analysis including the Bellmunt score (HR = 0.7, 95%CI [0.38-1.35], P = .5). CONCLUSION: The presence of ANA >1/160 is associated with iRAE and limiting toxicity of pembrolizumab.

Gemcitabine + Nab-paclitaxel or Gemcitabine alone after FOLFIRINOX failure in patients with metastatic pancreatic adenocarcinoma: a real-world AGEO study.

BACKGROUND: Gemcitabine (Gem) alone or with Nab-paclitaxel (Gem-Nab) is used as second-line treatment for metastatic pancreatic adenocarcinoma (mPA) after FOLFIRINOX (FFX) failure; however, no comparative data exist. This study evaluates the efficacy and safety of adding Nab-paclitaxel to Gem for mPA after FFX failure. METHODS: In this retrospective real-world multicenter study, from 2011 to 2019, patients with mPA receiving Gem-Nab (Gem 1000 mg/m² + Nab 125 mg/m², 3 out of 4 weeks) or Gem alone were included after progression on FFX. RESULTS: A total of 427 patients were included. Patients receiving Gem-Nab had more metastatic sites, peritoneal disease and less PS 2 (24% vs. 35%). After median follow-up of 22 months, Gem-Nab was associated with better disease control rate (DCR) (56% vs. 32%; P < 0.001), progression-free survival (PFS) (3.5 vs. 2.3 months; 95% CI: 0.43-0.65) and overall survival (OS) (7.1 vs. 4.7 months; 95% CI: 0.53-0.86). After multivariate analysis, Gem-Nab and PS 0/1 were associated with better OS and PFS. Grade 3/4 toxicity was more frequent with Gem-Nab (44% vs. 29%). CONCLUSION: In this study, Gem-Nab was associated with better DCR, PFS and OS compared with Gem alone in patients with mPA after FFX failure, at the cost of higher toxicity.

[Issues of oral targeted therapies in daily clinical practice: 5th edition of the congress of pharmacology of anticancer drugs]. / Enjeux et écueils des thérapies ciblées orales en pratique clinique quotidienne : 5e journée de pharmacologie des anti-tumoraux.

Oral targeted therapies are a growing class of medication. After clinical trials conducted on a selected population, these molecules are usually approved at a fixed dose. However, oral tyrosine kinase inhibitors are characterized by a large intra and inter-individual pharmacokinetic variability, and a narrow therapeutic index. Hence, their prescription is hazardous and unsafe in non-selected people from daily clinical practice. The increasing number of available targeted therapies point out new challenges. These challenges should especially concern prescription for out of the ordinary patients, rules for dose adjustment according to factors of frailty. The ultimate goal is to ensure a safe and individualized prescription. Moreover, many of these molecules are metabolized by the CYP3A4, leading to a serious risk of drug interaction. These interactions might involve not only conventional medicine but also alternative and complementary medicines. These latter are more and more common but oncologists often lack experience about them. Finally, the oral route raises the issues of adherence, and the question of its assessment should now become a permanent part of patients care.