2548 - Excess weight and efficacy of anti-PD-1 antibodies in advanced cancer patients

Background

Immunotherapy is a new and effective form of therapy in several types of cancer, although molecular predictors of response are limited. Recently, we have described that immune-related adverse-events (irAEs) are significantly associated with immunotherapy efficacy, and it has been suggested that body mass index (BMI) might be a favourable factor. We have studied whether excess weight influences the efficacy outcomes of immunotherapy and whether it is associated with immune-related adverse events. We have also evaluated the combined effect of overweight and irAEs.

Methods

We calculated BMI in patients treated with single-agent anti-PD-1 antibodies for advanced cancer. Efficacy of anti-PD-1 treatment was evaluated with both objective response (OR) rate, and progression-free survival (PFS), and toxicity with irAEs. We established the association between overweight and OR, PFS and irAEs.

Results

One hundred and thirty-two patients were included in the study. Primary malignancies were lung cancer (n = 93), melanoma (n = 12), head and neck carcinoma (n = 9), renal carcinoma (n = 6), urothelial carcinoma (n = 4), Hodgkin’s lymphoma (n = 3), and other cancers (n = 5). Median BMI was 24.9 kg/m2, and 64 patients (48.4%) were excess weight (BMI≥25 kg/m2). An OR was achieved in 50 patients (38.0%), and median PFS was 6 months. IrAEs occurred in 44 patients (33.3%). OR was significantly higher in excess weight patients that in patients with BMI <25 kg/m2 (51.6% vs 25.0%) (Odds Ratio 3.45, CI 95% 1.58-7.55, p = 0.0009). PFS was also significantly improved in excess weight patients (7.25 months vs 4 months, HR 1.72, CI 95% 1.12–2.64, p = 0.01). IrAEs were not more frequent in excess weight patients (54.5% vs 43.2%, p = 0.21). When BMI and irAES were combined, we observed a clear prognostic trend in OR rate (87.5% in overweight patients with irAEs, in contrast with 6.2% in patients with normal BMI) (OR 161.0, CI 95% 1.58-7.55 p < 0.00001), and PFS (14 months vs 3 months) (HR 5.89, p < 0.0001).

Conclusions

Excess weight patients with advanced cancer that receive single-agent anti-PD-1 antibody therapy exhibit a significantly improved clinical outcome compared with patients with normal BMI. This association was especially marked when BMI and irAEs were considered combined.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Instituto Investigacion Sanitaria Princesa.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.