Background Recent evidence suggested a potential correlation between overweight and the efficacy of immune checkpoint inhibitors (ICIs) in cancer patients. Patients and methods We conducted a retrospective study of advanced cancer patients consecutively treated with anti-PD-1/PD-L1 inhibitors, in order to compare clinical outcomes according to baseline BMI levels as primary analysis. Based on their BMI, patients were categorized into overweight/obese (≥ 25) and non-overweight (< 25). A gender analysis was also performed, using the same binomial cut-off. Further subgroup analyses were performed categorizing patients into underweight, normal weight, overweight and obese. Results Between September 2013 and May 2018, 976 patients were evaluated. The median age was 68 years, male/female ratio was 663/313. Primary tumors were: NSCLC (65.1%), melanoma (18.7%), renal cell carcinoma (13.8%) and others (2.4%). ECOG-PS was ≥2 in 145 patients (14.9%). PD-1/PD-L1 inhibitors were administered as first-line treatment in 26.6% of cases. Median BMI was 24.9: 492 patients (50.6%) were non-overweight, 480 patients (50.4%) were overweight/obese. 25.2% of non-overweight patients experienced irAEs of any grade, while 55.6% of overweight/obese patients ( p < 0.0001). ORR was significantly higher in overweight/obese patients compared to non-overweight (p < 0.0001). Median follow-up was 17.2 months. Median TTF, PFS and OS were significantly longer for overweight/obese patients in univariate (p < 0.0001, for all the survival intervals) and multivariate models ( p = 0.0009, p < 0.0001 and p < 0.0001 respectively). The significance was confirmed in both sex, except for PFS in male patients ( p = 0.0668). Conclusions Overweight could be considered a tumorigenic immune-dysfunction that could be effectively reversed by ICIs. BMI could be a useful predictive tool in clinical practice and a stratification factor in prospective clinical trials with ICIs. Electronic supplementary material The online version of this article (10.1186/s40425-019-0527-y) contains supplementary material, which is available to authorized users.

Background Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors. Materials and Methods Consecutive patients with advanced cancer, treated with anti‐programmed death‐1 (PD‐1) agents, were evaluated according to the presence of pre‐existing AIDs. The incidence of immune‐related adverse events (irAEs) and clinical outcomes were compared among subgroups. Results A total of 751 patients were enrolled; median age was 69 years. Primary tumors were as follows: non‐small cell lung cancer, 492 (65.5%); melanoma, 159 (21.2%); kidney cancer, 94 (12.5%); and others, 6 (0.8%). Male/female ratio was 499/252. Eighty‐five patients (11.3%) had pre‐existing AIDs, further differentiated in clinically active (17.6%) and inactive (82.4%). Among patients with pre‐existing AIDs, incidence of irAEs of any grade was significantly higher when compared with patients without AIDs (65.9% vs. 39.9%). At multivariate analysis, both inactive (p = .0005) and active pre‐existing AIDs (p = .0162), female sex (p = .0004), and Eastern Cooperative Oncology Group Performance Status <2 (p = .0030) were significantly related to a higher incidence of irAEs of any grade. No significant differences were observed regarding grade 3/4 irAEs and objective response rate among subgroups. Pre‐existing AIDs were not significantly related with progression‐free survival and overall survival. Conclusion This study quantifies the increased risk of developing irAEs in patients with pre‐existing AIDs who had to be treated with anti‐PD‐1 immunotherapy. Nevertheless, the incidence of grade 3/4 irAEs is not significantly higher when compared with control population. The finding of a greater incidence of irAEs among female patients ranks among the “hot topics” in gender‐related differences in immuno‐oncology. Implications for Practice Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors but are frequent in clinical practice. This study quantifies the increased risk of developing immune‐related adverse events (irAEs) in patients with pre‐existing AIDs who had to be treated with anti‐programmed death‐1 immunotherapy. Nevertheless, their toxicities are mild and the incidence of grade 3/4 irAEs is not significantly higher compared with those of controls. These results will help clinicians in everyday practice, improving their ability to offer a proper counselling to patients, in order to offer an immunotherapy treatment even to patients with pre‐existing autoimmune disease.

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BackgroundThis phase II study investigated efficacy and safety of weekly alternating Bevacizumab (BEV)/Irinotecan (CPT-11) or Oxaliplatin (OHP) associated to weekly 5-Fluorouracil (5-FU) in first line treatment of metastatic colorectal carcinoma (MCRC).MethodsSimon two-step design: delta 20% (p0 50%, p1 70%), power 80%, α 5%, β 20%. Projected objective responses (ORR): I step, 8/15 patients (pts); II step 26/43 pts. Schedule: weekly 12 h-timed-flat-infusion/5-FU 900 mg/m2, days 1-2, 8-9, 15-16, 22-23; CPT-11 160 mg/m2 plus BEV 5 mg/kg, days 1,15; OHP at three dose-levels, 60-70-80 mg/m2, days 8, 22; every 4 weeks.ResultsFifty consecutive, unselected pts < 75 years were enrolled: median age 63; young-elderly (yE) 24 (48%); liver metastases (LM) 33 pts, 66% Achieved OHP recommended dose, 80 mg/m2. ORR 82% intent-to-treat and 84% as-treated analysis. Median progression-free survival 12 months. Equivalent efficacy was obtained in yE pts. Liver metastasectomies were performed in 26% of all pts and in 39% of pts with LM. After a median follow-up of 21 months, median overall survival was 28 months. Cumulative G3-4 toxicities per patient: diarrhea 28%, mucositis 6%, neutropenia 10%, hypertension 2%. They were equivalent in yE pts. Limiting toxicity syndromes (LTS), consisting of the dose-limiting toxicity, associated or not to G2 or limiting toxicities: 44% overall, 46% in yE. Multiple versus single site LTS, respectively: overall, 24% versus 20%; yE pts, 37.5% versus 8%.ConclusionPoker combination shows high activity and efficacy in first line treatment of MCRC. It increases liver metastasectomies rate and can be safely administered.Trial registrationOsservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali (OsSC) Agenzia Italiana del Farmaco (AIFA) Numero EudraCT 2007-004946-34