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Multicenter Study
. 2019 Feb 27;7(1):57.
doi: 10.1186/s40425-019-0527-y.

A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable

Alessio Cortellini  1   2   3 , Melissa Bersanelli  4   5 , Sebastiano Buti  4 , Katia Cannita  6 , Daniele Santini  7 , Fabiana Perrone  4 , Raffaele Giusti  8 , Marcello Tiseo  4   5 , Maria Michiara  4 , Pietro Di Marino  9 , Nicola Tinari  10 , Michele De Tursi  10 , Federica Zoratto  11 , Enzo Veltri  11 , Riccardo Marconcini  12 , Francesco Malorgio  13 , Marco Russano  7 , Cecilia Anesi  7 , Tea Zeppola  7 , Marco Filetti  8 , Paolo Marchetti  8   14 , Andrea Botticelli  8 , Gian Carlo Antonini Cappellini  14 , Federica De Galitiis  14 , Maria Giuseppa Vitale  15 , Francesca Rastelli  16 , Federica Pergolesi  16 , Rossana Berardi  17 , Silvia Rinaldi  17 , Marianna Tudini  18 , Rosa Rita Silva  18 , Annagrazia Pireddu  19 , Francesco Atzori  19 , Rita Chiari  20 , Biagio Ricciuti  20 , Andrea De Giglio  20 , Daniela Iacono  21 , Alain Gelibter  22 , Mario Alberto Occhipinti  22 , Alessandro Parisi  23   6 , Giampiero Porzio  23   6 , Maria Concetta Fargnoli  6   24 , Paolo Antonio Ascierto  25 , Corrado Ficorella  23   6 , Clara Natoli  10
Affiliations
Multicenter Study

A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable

Alessio Cortellini et al. J Immunother Cancer. .

Abstract

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.

Keywords: Anti-PD-1/PD-L1; BMI; Cancer; Immunotherapy; Obesity; Overweight.

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Conflict of interest statement

Ethics approval and consent to participate

All patients provided written, informed consent to treatment with immunotherapy. All patients alive at the time of data collection provided an informed consent for the present retrospective analysis. The procedures followed were in accordance with the precepts of Good Clinical Practice and the declaration of Helsinki. The study was approved by the respective local ethical committees on human experimentation of each institution, after previous approval by the coordinating center (University of L’Aquila, Internal Review Board protocol number 32865, approved on July 24th, 2018).

Consent for publication

Not applicable.

Competing interests

Dr Alessio Cortellini received grants as speaker by MSD, Astra-Zeneca and Boehringer Ingelheim, gran consultancies by BMS and Ipsen; dr Marcello Tiseo received grant as speaker and advisory role by Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Pierre Fabre; dr Maria Giuseppa Vitale received travel grants and speaker fees by BMS, Ipsen Astellas, Jansen, Novartis and Pfizer; dr Sebatiano Buti received grants as speaker and advisory role by BMS, Pfizer, MSD, Ipsen, Novartis, Astra-Zeneca; dr. Melissa Bersanelli received honoraria as speaker at scientific events and as consultant for advisory role by BMS and Pfizer.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Kaplan-Meier survival curves according to binomial BMI levels (cut-off 25). (a) Time to Treatment Failure. BMI < 25: 3.6 months (95% CI: 3.2–4.1); BMI ≥ 25: 9.3 months (95%CI: 8.1–11.6). (b) Progression Free Survival. BMI < 25: 3.7 months (95% CI: 3.2–4.1); BMI ≥ 25: 11.7 months (95% CI: 9.4–15). (C) Overall Survival. BMI < 25: 6.6 months (95% CI: 5.8–8.5); BMI ≥ 25: 26.6 months (95% CI: 21.4–36.8)
Fig. 2
Fig. 2
Kaplan-Meier survival curves according to BMI levels (non-overweight BMI < 25, overweight BMI 25–30, obese BMI ≥ 30). (a) Time to Treatment Failure. BMI < 25: 3.6 months (95% CI: 3.2–4.1); BMI 25–30: 10.3 months (95%CI: 8.2–4.1); BMI ≥ 30: 7.3 months (95%CI: 5.5–11.7). (b) Progression Free Survival. BMI < 25: 3.7 months (95% CI: 3.2–4.1); BMI 25–30: 11.2 months (95%CI: 9.1–15.6); BMI ≥ 30: 12.9 months (95%CI: 7.1–18). (c) Overall Survival. BMI < 25: 6.6 months (95% CI: 5.8–8.5); BMI 25–30: 26.6 months (95%CI: 21.4–36.8); BMI ≥ 30: not reached
Fig. 3
Fig. 3
Kaplan-Meier survival curves according to BMI levels (normal weight BMI 18.5–25, overweight BMI 25–30, obese BMI ≥ 30). (a) Time to Treatment Failure. BMI 18.5–25: 3.9 months (95% CI: 3.4–5.0); BMI 25–30: 10.3 months (95%CI: 8.2–4.1); BMI ≥ 30: 7.3 months (95%CI: 5.5–11.7). (b) Progression Free Survival. BMI 18.5–25: 4.4 months (95% CI: 3.6–5.3); BMI 25–30: 11.2 months (95%CI: 9.1–15.6); BMI ≥ 30: 12.9 months (95%CI: 7.1–18). (c) Overall Survival. BMI 18.5–25: 7.9 months (95% CI: 6.4–9.8); BMI 25–30: 26.6 months (95%CI: 21.4–36.8); BMI ≥ 30: not reached
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