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.

A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: When overweight becomes favorable / Cortellini, A.; Bersanelli, M.; Buti, S.; Cannita, K.; Santini, D.; Perrone, F.; Giusti, R.; Tiseo, M.; Michiara, M.; Di Marino, P.; Tinari, N.; De Tursi, M.; Zoratto, F.; Veltri, E.; Marconcini, R.; Malorgio, F.; Russano, M.; Anesi, C.; Zeppola, T.; Filetti, M.; Marchetti, P.; Botticelli, A.; Antonini Cappellini, G. C.; De Galitiis, F.; Vitale, M. G.; Rastelli, F.; Pergolesi, F.; Berardi, R.; Rinaldi, S.; Tudini, M.; Silva, R. R.; Pireddu, A.; Atzori, F.; Chiari, R.; Ricciuti, B.; De Giglio, A.; Iacono, D.; Gelibter, A.; Occhipinti, M.; Parisi, A.; Porzio, G.; Fargnoli, M. C.; Ascierto, P. A.; Ficorella, C.; Natoli, C.. - In: JOURNAL FOR IMMUNOTHERAPY OF CANCER. - ISSN 2051-1426. - 7:1(2019), p. 57. [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

Santini D.;Zoratto F.;Filetti M.;Marchetti P.;Botticelli A.;Gelibter A.;Occhipinti M.;
2019

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.
2019
Anti-PD-1/PD-L1; BMI; Cancer; Immunotherapy; Obesity; Overweight
01 Pubblicazione su rivista::01a Articolo in rivista
A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: When overweight becomes favorable / Cortellini, A.; Bersanelli, M.; Buti, S.; Cannita, K.; Santini, D.; Perrone, F.; Giusti, R.; Tiseo, M.; Michiara, M.; Di Marino, P.; Tinari, N.; De Tursi, M.; Zoratto, F.; Veltri, E.; Marconcini, R.; Malorgio, F.; Russano, M.; Anesi, C.; Zeppola, T.; Filetti, M.; Marchetti, P.; Botticelli, A.; Antonini Cappellini, G. C.; De Galitiis, F.; Vitale, M. G.; Rastelli, F.; Pergolesi, F.; Berardi, R.; Rinaldi, S.; Tudini, M.; Silva, R. R.; Pireddu, A.; Atzori, F.; Chiari, R.; Ricciuti, B.; De Giglio, A.; Iacono, D.; Gelibter, A.; Occhipinti, M.; Parisi, A.; Porzio, G.; Fargnoli, M. C.; Ascierto, P. A.; Ficorella, C.; Natoli, C.. - In: JOURNAL FOR IMMUNOTHERAPY OF CANCER. - ISSN 2051-1426. - 7:1(2019), p. 57. [10.1186/s40425-019-0527-y]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1484842
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