Body mass index (BMI) and outcome of metastatic melanoma patients receiving targeted therapy and immunotherapy: a multicenter international retrospective study

Abstract

BackgroundObesity is a risk factor for malignancy; however, its prognostic role in patients with metastatic melanoma is controversial. We aim to investigate the prognostic role of body mass index (BMI) in patients with metastatic melanoma receiving mitogen-activated pathway kinase inhibitors (MAPKi), immune checkpoint inhibitors (ICIs) alone or their sequence.MethodsData on patients with metastatic melanoma receiving ≥1 line of systemic treatment were retrieved from prospectively collected databases. Progression-free survival (PFS) and overall survival (OS) were analyzed by means of multivariable stratified Cox regression models; disease control rate (DCR) was analyzed by multivariable stratified logistic regression models. Subgroup analyzes according to the type of treatments received, and in BRAF-mutated patients were pre-planned. All multivariable models included BMI, age, gender, American Joint Committee on Cancer stage, performance status, lactate dehydrogenase and treatment sequencing strategy as covariates.ResultsBetween November 2010 and November 2018, 688 patients from three Italian and two Polish centers were enrolled. 379 (57%) patients had M1c/d disease, 273 (41%) were female and the mean BMI was 27.1 (SD=4.9). Considering first-line treatment, 446 patients (66.8%) received ICIs and 222 MAPKi. No impact of BMI on OS was detected either considering the first line of ICIs, or ICIs sequencing (HR=1.02, 95% CI: 0.99 to 1.05, p=0.202, and HR=1.02, 95% CI: 0.99 to 1.04, p=0.237, respectively). A late effect of BMI on OS was found in patients treated with MAPKi: for five units increment, a 51% of risk reduction at 18 months and a 76% of risk reduction at 30 months were observed. No significant effect of BMI on PFS and DCR was found in any of the subgroup analyzes.ConclusionIn patients with metastatic melanoma receiving ICIs, there is no impact of BMI on DCR, PFS and OS. The late prognostic effect of BMI in patients treated with MAPKi should be considered hypothesis generating and needs to be further investigated.

Impact of BMI on Survival Outcomes of Immunotherapy in Solid Tumors: A Systematic Review

“…The remaining 26 studies were subsequently reviewed and screened according to our inclusion and exclusion criteria. Finally, 18 studies were included in our systematic review ( Figure 2 ) [ 18 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. The included studies were published between 2018 and 2020, and were retrospective studies, either single or multicenter; one study was a pooled analysis of patients treated with immunotherapy in the context of phase 2 and 3 trials.…”

“…The study by McQuade et al is the only large multicenter study ( n = 331) supporting a positive association of high BMI with improved outcomes, however only in male patients receiving anti-PD1 or PD-L1 (PFS HR 0.69 (95% CI 0.45–1.06), p = 0.07; OS HR 0.69 (95% CI 0.42–1.12); p = 0.84) [ 18 ]. Overall, two studies, making the largest sample size (total n = 704), reported no association of BMI with disease response and survival [ 21 , 24 ]. In the study by Rutkowski et al, BMI was not associated with disease control rate (DCR) (adjusted OR 0.98 (95% CI 0.93–1.03); p = 0.432), PFS (HR 1.00 (95% CI 0.98–1.03) p = 0.732), nor OS (HR 1.02 (95% CI 0.99–1.05); p = 0.202) [ 21 ].…”

“…Overall, two studies, making the largest sample size (total n = 704), reported no association of BMI with disease response and survival [ 21 , 24 ]. In the study by Rutkowski et al, BMI was not associated with disease control rate (DCR) (adjusted OR 0.98 (95% CI 0.93–1.03); p = 0.432), PFS (HR 1.00 (95% CI 0.98–1.03) p = 0.732), nor OS (HR 1.02 (95% CI 0.99–1.05); p = 0.202) [ 21 ]. Similarly, Young et al reported no differences in DCR (OR 0.58 (95% CI 0.31–1.09); p = 0.09), PFS (HR 1.28 (95% CI 0.90–1.83); p = 0.18), and OS (HR 1.10 (95% CI 0.72–1.67); p = 0.65), according to BMI [ 24 ].…”

“…This leads to difficult interpretation of clinical results, which can vary over time according to the correlation of BMI with response and outcomes at different timepoints. Pretreatment BMI trends and dynamic on-treatment evaluation, rather than single baseline assessment, can more accurately reflect patients’ nutritional status and general conditions [ 21 ].…”

Body Mass Index in Patients Treated with Cabozantinib for Advanced Renal Cell Carcinoma: A New Prognostic Factor?

“…Beyond its well-known role as a risk factor for the development of RCC, obesity is also emerging as a potential key factor for response to therapy [ 3 ]. A growing body of evidence suggests that being overweight and obese are associated with better outcome in cancer patients treated with immunotherapy [ 4 , 5 ]. In this regard, Sanchez et al investigated the angiogenic and immunologic transcriptomic profiles of the primary tumor and perinephric adipose tissue in normal weight and obese RCC patients.…”