Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50.

Alessio Cortellini; Marcello Tiseo; Giuseppe L. Banna; Federico Cappuzzo; Joachim G. J. V. Aerts; Fausto Barbieri; Raffaele Giusti; Emilio Bria; Diego Cortinovis; Francesco Grossi; Maria R. Migliorino; Domenico Galetta; Francesco Passiglia; Daniele Santini; Rossana Berardi; Alessandro Morabito; Carlo Genova; Francesca Mazzoni; Vincenzo Di Noia; Diego Signorelli; Alessandro Tuzi; Alain Gelibter; Paolo Marchetti; Marianna Macerelli; Francesca Rastelli; Rita Chiari; Danilo Rocco; Stefania Gori; Michele De Tursi; Giovanni Mansueto; Federica Zoratto; Matteo Santoni; Marianna Tudini; Erika Rijavec; Marco Filetti; Annamaria Catino; Pamela Pizzutilo; Luca Sala; Fabrizio Citarella; Russano Marco; Mariangela Torniai; Luca Cantini; Giada Targato; Vincenzo Sforza; Olga Nigro; Miriam G. Ferrara; Ettore D'Argento; Sebastiano Buti; Paola Bordi; Lorenzo Antonuzzo; Simona Scodes; Lorenza Landi; Giorgia Guaitoli; Cinzia Baldessari; Luigi Della Gravara; Maria Giovanna Dal Bello; Robert A. Belderbos; Paolo Bironzo; Simona Carnio; Serena Ricciardi; Alessio Grieco; Alessandro De Toma; Claudia Proto; Alex Friedlaender; Ornella Cantale; Biagio Ricciuti; Alfredo Addeo; Giulio Metro; Corrado Ficorella; Giampiero Porzio

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50.

Alessio Cortellini, Marcello Tiseo, Giuseppe L. Banna, Federico Cappuzzo, Joachim G. J. V. Aerts, Fausto Barbieri, Raffaele Giusti, Emilio Bria, Diego Cortinovis, Francesco Grossi, Maria R. Migliorino, Domenico Galetta, Francesco Passiglia, Daniele Santini, Rossana Berardi, Alessandro Morabito, Carlo Genova, Francesca Mazzoni, Vincenzo Di Noia, Diego SignorelliAlessandro Tuzi, Alain Gelibter, Paolo Marchetti, Marianna Macerelli, Francesca Rastelli, Rita Chiari, Danilo Rocco, Stefania Gori, Michele De Tursi, Giovanni Mansueto, Federica Zoratto, Matteo Santoni, Marianna Tudini, Erika Rijavec, Marco Filetti, Annamaria Catino, Pamela Pizzutilo, Luca Sala, Fabrizio Citarella, Russano Marco, Mariangela Torniai, Luca Cantini, Giada Targato, Vincenzo Sforza, Olga Nigro, Miriam G. Ferrara, Ettore D'Argento, Sebastiano Buti, Paola Bordi, Lorenzo Antonuzzo, Simona Scodes, Lorenza Landi, Giorgia Guaitoli, Cinzia Baldessari, Luigi Della Gravara, Maria Giovanna Dal Bello, Robert A. Belderbos, Paolo Bironzo, Simona Carnio, Serena Ricciardi, Alessio Grieco, Alessandro De Toma, Claudia Proto, Alex Friedlaender, Ornella Cantale, Biagio Ricciuti, Alfredo Addeo, Giulio Metro, Corrado Ficorella, Giampiero Porzio

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Single-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50 We conducted a multicenter retrospective study aimed at evaluating the clinicopathologic correlates of pembrolizumab effectiveness in patients with treatment-naïve NSCLC and a PD-L1 expression of ≥ 50 One thousand and twenty-six consecutive patients were included. The objective response rate (ORR) was 44.5950.2-49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95.9-9.5; 599 events) and 17.2 months (955.3-22.3; 598 censored patients), respectively. ECOG-PS ≥ 2 (p textless 0.0001) and bone metastases (p = 0.0003) were confirmed to be independent predictors of a worse ORR. Former smokers (p = 0.0002), but not current smokers (p = 0.0532) were confirmed to have a significantly prolonged PFS compared to never smokers at multivariate analysis. ECOG-PS (p textless 0.0001), bone metastases (p textless 0.0001) and liver metastases (p textless 0.0001) were also confirmed to be independent predictors of a worse PFS. Previous palliative RT was significantly related to a shortened OS (p = 0.0104), while previous non-palliative RT was significantly related to a prolonged OS (p = 0.0033). Former smokers (p = 0.0131), but not current smokers (p = 0.3433) were confirmed to have a significantly prolonged OS compared to never smokers. ECOG-PS (p textless 0.0001), bone metastases (p textless 0.0001) and liver metastases (p textless 0.0001) were also confirmed to be independent predictors of a shortened OS. A PD-L1 expression of ≥ 90 as assessed by recursive partitioning, was associated with significantly higher ORR (p = 0.0204), and longer and OS (p = 0.0346) at multivariable analysis. CONCLUSION: Pembrolizumab was effective in a large cohort of NSCLC patients treated outside of clinical trials. Questions regarding the effectiveness in clinical subgroups, such as patients with poorer PS and with liver/bone metastases, still remain to be addressed. We confirmed that the absence of tobacco exposure, and the presence of bone and liver metastasis are associated with worse clinical outcomes to pembrolizumab. Increasing levels of PD-L1 expression may help identifying a subset of patients who derive a greater benefit from pembrolizumab monotherapy.

Original language	English
Journal	Cancer Immunology and Immunotherapy
Issue number	11
Publication status	Published - Nov 1 2020

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Cortellini, A., Tiseo, M., Banna, G. L., Cappuzzo, F., Aerts, J. G. J. V., Barbieri, F., Giusti, R., Bria, E., Cortinovis, D., Grossi, F., Migliorino, M. R., Galetta, D., Passiglia, F., Santini, D., Berardi, R., Morabito, A., Genova, C., Mazzoni, F., Di Noia, V., ... Porzio, G. (2020). Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. Cancer Immunology and Immunotherapy, (11).

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. / Cortellini, Alessio; Tiseo, Marcello; Banna, Giuseppe L.; Cappuzzo, Federico; Aerts, Joachim G. J. V.; Barbieri, Fausto; Giusti, Raffaele; Bria, Emilio; Cortinovis, Diego; Grossi, Francesco; Migliorino, Maria R.; Galetta, Domenico; Passiglia, Francesco; Santini, Daniele; Berardi, Rossana; Morabito, Alessandro ; Genova, Carlo; Mazzoni, Francesca; Di Noia, Vincenzo; Signorelli, Diego; Tuzi, Alessandro; Gelibter, Alain; Marchetti, Paolo; Macerelli, Marianna; Rastelli, Francesca; Chiari, Rita; Rocco, Danilo; Gori, Stefania; De Tursi, Michele; Mansueto, Giovanni; Zoratto, Federica; Santoni, Matteo; Tudini, Marianna; Rijavec, Erika; Filetti, Marco; Catino, Annamaria ; Pizzutilo, Pamela ; Sala, Luca; Citarella, Fabrizio; Marco, Russano; Torniai, Mariangela; Cantini, Luca; Targato, Giada; Sforza, Vincenzo; Nigro, Olga; Ferrara, Miriam G.; D'Argento, Ettore; Buti, Sebastiano; Bordi, Paola; Antonuzzo, Lorenzo; Scodes, Simona; Landi, Lorenza; Guaitoli, Giorgia; Baldessari, Cinzia; Della Gravara, Luigi; Dal Bello, Maria Giovanna; Belderbos, Robert A.; Bironzo, Paolo; Carnio, Simona; Ricciardi, Serena; Grieco, Alessio; De Toma, Alessandro; Proto, Claudia; Friedlaender, Alex; Cantale, Ornella; Ricciuti, Biagio; Addeo, Alfredo; Metro, Giulio; Ficorella, Corrado; Porzio, Giampiero.

In: Cancer Immunology and Immunotherapy, No. 11, 01.11.2020.

Research output: Contribution to journal › Article › peer-review

Cortellini, A, Tiseo, M, Banna, GL, Cappuzzo, F, Aerts, JGJV, Barbieri, F, Giusti, R, Bria, E, Cortinovis, D, Grossi, F, Migliorino, MR, Galetta, D, Passiglia, F, Santini, D, Berardi, R, Morabito, A , Genova, C, Mazzoni, F, Di Noia, V, Signorelli, D, Tuzi, A, Gelibter, A, Marchetti, P, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Gori, S, De Tursi, M, Mansueto, G, Zoratto, F, Santoni, M, Tudini, M, Rijavec, E, Filetti, M, Catino, A , Pizzutilo, P , Sala, L, Citarella, F, Marco, R, Torniai, M, Cantini, L, Targato, G, Sforza, V, Nigro, O, Ferrara, MG, D'Argento, E, Buti, S, Bordi, P, Antonuzzo, L, Scodes, S, Landi, L, Guaitoli, G, Baldessari, C, Della Gravara, L, Dal Bello, MG, Belderbos, RA, Bironzo, P, Carnio, S, Ricciardi, S, Grieco, A, De Toma, A, Proto, C, Friedlaender, A, Cantale, O, Ricciuti, B, Addeo, A, Metro, G, Ficorella, C & Porzio, G 2020, 'Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50.', Cancer Immunology and Immunotherapy, no. 11.

Cortellini, Alessio ; Tiseo, Marcello ; Banna, Giuseppe L. ; Cappuzzo, Federico ; Aerts, Joachim G. J. V. ; Barbieri, Fausto ; Giusti, Raffaele ; Bria, Emilio ; Cortinovis, Diego ; Grossi, Francesco ; Migliorino, Maria R. ; Galetta, Domenico ; Passiglia, Francesco ; Santini, Daniele ; Berardi, Rossana ; Morabito, Alessandro ; Genova, Carlo ; Mazzoni, Francesca ; Di Noia, Vincenzo ; Signorelli, Diego ; Tuzi, Alessandro ; Gelibter, Alain ; Marchetti, Paolo ; Macerelli, Marianna ; Rastelli, Francesca ; Chiari, Rita ; Rocco, Danilo ; Gori, Stefania ; De Tursi, Michele ; Mansueto, Giovanni ; Zoratto, Federica ; Santoni, Matteo ; Tudini, Marianna ; Rijavec, Erika ; Filetti, Marco ; Catino, Annamaria ; Pizzutilo, Pamela ; Sala, Luca ; Citarella, Fabrizio ; Marco, Russano ; Torniai, Mariangela ; Cantini, Luca ; Targato, Giada ; Sforza, Vincenzo ; Nigro, Olga ; Ferrara, Miriam G. ; D'Argento, Ettore ; Buti, Sebastiano ; Bordi, Paola ; Antonuzzo, Lorenzo ; Scodes, Simona ; Landi, Lorenza ; Guaitoli, Giorgia ; Baldessari, Cinzia ; Della Gravara, Luigi ; Dal Bello, Maria Giovanna ; Belderbos, Robert A. ; Bironzo, Paolo ; Carnio, Simona ; Ricciardi, Serena ; Grieco, Alessio ; De Toma, Alessandro ; Proto, Claudia ; Friedlaender, Alex ; Cantale, Ornella ; Ricciuti, Biagio ; Addeo, Alfredo ; Metro, Giulio ; Ficorella, Corrado ; Porzio, Giampiero. / Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. In: Cancer Immunology and Immunotherapy. 2020 ; No. 11.

@article{5964277a5a144e10b781b460827cd8e1,

title = "Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50.",

abstract = "BACKGROUND: Single-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50 We conducted a multicenter retrospective study aimed at evaluating the clinicopathologic correlates of pembrolizumab effectiveness in patients with treatment-na{\"i}ve NSCLC and a PD-L1 expression of ≥ 50 One thousand and twenty-six consecutive patients were included. The objective response rate (ORR) was 44.5950.2-49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95.9-9.5; 599 events) and 17.2 months (955.3-22.3; 598 censored patients), respectively. ECOG-PS ≥ 2 (p textless 0.0001) and bone metastases (p = 0.0003) were confirmed to be independent predictors of a worse ORR. Former smokers (p = 0.0002), but not current smokers (p = 0.0532) were confirmed to have a significantly prolonged PFS compared to never smokers at multivariate analysis. ECOG-PS (p textless 0.0001), bone metastases (p textless 0.0001) and liver metastases (p textless 0.0001) were also confirmed to be independent predictors of a worse PFS. Previous palliative RT was significantly related to a shortened OS (p = 0.0104), while previous non-palliative RT was significantly related to a prolonged OS (p = 0.0033). Former smokers (p = 0.0131), but not current smokers (p = 0.3433) were confirmed to have a significantly prolonged OS compared to never smokers. ECOG-PS (p textless 0.0001), bone metastases (p textless 0.0001) and liver metastases (p textless 0.0001) were also confirmed to be independent predictors of a shortened OS. A PD-L1 expression of ≥ 90 as assessed by recursive partitioning, was associated with significantly higher ORR (p = 0.0204), and longer and OS (p = 0.0346) at multivariable analysis. CONCLUSION: Pembrolizumab was effective in a large cohort of NSCLC patients treated outside of clinical trials. Questions regarding the effectiveness in clinical subgroups, such as patients with poorer PS and with liver/bone metastases, still remain to be addressed. We confirmed that the absence of tobacco exposure, and the presence of bone and liver metastasis are associated with worse clinical outcomes to pembrolizumab. Increasing levels of PD-L1 expression may help identifying a subset of patients who derive a greater benefit from pembrolizumab monotherapy.",

author = "Alessio Cortellini and Marcello Tiseo and Banna, {Giuseppe L.} and Federico Cappuzzo and Aerts, {Joachim G. J. V.} and Fausto Barbieri and Raffaele Giusti and Emilio Bria and Diego Cortinovis and Francesco Grossi and Migliorino, {Maria R.} and Domenico Galetta and Francesco Passiglia and Daniele Santini and Rossana Berardi and Alessandro Morabito and Carlo Genova and Francesca Mazzoni and {Di Noia}, Vincenzo and Diego Signorelli and Alessandro Tuzi and Alain Gelibter and Paolo Marchetti and Marianna Macerelli and Francesca Rastelli and Rita Chiari and Danilo Rocco and Stefania Gori and {De Tursi}, Michele and Giovanni Mansueto and Federica Zoratto and Matteo Santoni and Marianna Tudini and Erika Rijavec and Marco Filetti and Annamaria Catino and Pamela Pizzutilo and Luca Sala and Fabrizio Citarella and Russano Marco and Mariangela Torniai and Luca Cantini and Giada Targato and Vincenzo Sforza and Olga Nigro and Ferrara, {Miriam G.} and Ettore D'Argento and Sebastiano Buti and Paola Bordi and Lorenzo Antonuzzo and Simona Scodes and Lorenza Landi and Giorgia Guaitoli and Cinzia Baldessari and {Della Gravara}, Luigi and {Dal Bello}, {Maria Giovanna} and Belderbos, {Robert A.} and Paolo Bironzo and Simona Carnio and Serena Ricciardi and Alessio Grieco and {De Toma}, Alessandro and Claudia Proto and Alex Friedlaender and Ornella Cantale and Biagio Ricciuti and Alfredo Addeo and Giulio Metro and Corrado Ficorella and Giampiero Porzio",

note = "Place: Germany",

year = "2020",

month = nov,

day = "1",

language = "English",

journal = "Cancer Immunology and Immunotherapy",

issn = "0340-7004",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "11",

}

TY - JOUR

T1 - Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50.

AU - Cortellini, Alessio

AU - Tiseo, Marcello

AU - Banna, Giuseppe L.

AU - Cappuzzo, Federico

AU - Aerts, Joachim G. J. V.

AU - Barbieri, Fausto

AU - Giusti, Raffaele

AU - Bria, Emilio

AU - Cortinovis, Diego

AU - Grossi, Francesco

AU - Migliorino, Maria R.

AU - Galetta, Domenico

AU - Passiglia, Francesco

AU - Santini, Daniele

AU - Berardi, Rossana

AU - Morabito, Alessandro

AU - Genova, Carlo

AU - Mazzoni, Francesca

AU - Di Noia, Vincenzo

AU - Signorelli, Diego

AU - Tuzi, Alessandro

AU - Gelibter, Alain

AU - Marchetti, Paolo

AU - Macerelli, Marianna

AU - Rastelli, Francesca

AU - Chiari, Rita

AU - Rocco, Danilo

AU - Gori, Stefania

AU - De Tursi, Michele

AU - Mansueto, Giovanni

AU - Zoratto, Federica

AU - Santoni, Matteo

AU - Tudini, Marianna

AU - Rijavec, Erika

AU - Filetti, Marco

AU - Catino, Annamaria

AU - Pizzutilo, Pamela

AU - Sala, Luca

AU - Citarella, Fabrizio

AU - Marco, Russano

AU - Torniai, Mariangela

AU - Cantini, Luca

AU - Targato, Giada

AU - Sforza, Vincenzo

AU - Nigro, Olga

AU - Ferrara, Miriam G.

AU - D'Argento, Ettore

AU - Buti, Sebastiano

AU - Bordi, Paola

AU - Antonuzzo, Lorenzo

AU - Scodes, Simona

AU - Landi, Lorenza

AU - Guaitoli, Giorgia

AU - Baldessari, Cinzia

AU - Della Gravara, Luigi

AU - Dal Bello, Maria Giovanna

AU - Belderbos, Robert A.

AU - Bironzo, Paolo

AU - Carnio, Simona

AU - Ricciardi, Serena

AU - Grieco, Alessio

AU - De Toma, Alessandro

AU - Proto, Claudia

AU - Friedlaender, Alex

AU - Cantale, Ornella

AU - Ricciuti, Biagio

AU - Addeo, Alfredo

AU - Metro, Giulio

AU - Ficorella, Corrado

AU - Porzio, Giampiero

N1 - Place: Germany

PY - 2020/11/1

Y1 - 2020/11/1

N2 - BACKGROUND: Single-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50 We conducted a multicenter retrospective study aimed at evaluating the clinicopathologic correlates of pembrolizumab effectiveness in patients with treatment-naïve NSCLC and a PD-L1 expression of ≥ 50 One thousand and twenty-six consecutive patients were included. The objective response rate (ORR) was 44.5950.2-49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95.9-9.5; 599 events) and 17.2 months (955.3-22.3; 598 censored patients), respectively. ECOG-PS ≥ 2 (p textless 0.0001) and bone metastases (p = 0.0003) were confirmed to be independent predictors of a worse ORR. Former smokers (p = 0.0002), but not current smokers (p = 0.0532) were confirmed to have a significantly prolonged PFS compared to never smokers at multivariate analysis. ECOG-PS (p textless 0.0001), bone metastases (p textless 0.0001) and liver metastases (p textless 0.0001) were also confirmed to be independent predictors of a worse PFS. Previous palliative RT was significantly related to a shortened OS (p = 0.0104), while previous non-palliative RT was significantly related to a prolonged OS (p = 0.0033). Former smokers (p = 0.0131), but not current smokers (p = 0.3433) were confirmed to have a significantly prolonged OS compared to never smokers. ECOG-PS (p textless 0.0001), bone metastases (p textless 0.0001) and liver metastases (p textless 0.0001) were also confirmed to be independent predictors of a shortened OS. A PD-L1 expression of ≥ 90 as assessed by recursive partitioning, was associated with significantly higher ORR (p = 0.0204), and longer and OS (p = 0.0346) at multivariable analysis. CONCLUSION: Pembrolizumab was effective in a large cohort of NSCLC patients treated outside of clinical trials. Questions regarding the effectiveness in clinical subgroups, such as patients with poorer PS and with liver/bone metastases, still remain to be addressed. We confirmed that the absence of tobacco exposure, and the presence of bone and liver metastasis are associated with worse clinical outcomes to pembrolizumab. Increasing levels of PD-L1 expression may help identifying a subset of patients who derive a greater benefit from pembrolizumab monotherapy.

AB - BACKGROUND: Single-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50 We conducted a multicenter retrospective study aimed at evaluating the clinicopathologic correlates of pembrolizumab effectiveness in patients with treatment-naïve NSCLC and a PD-L1 expression of ≥ 50 One thousand and twenty-six consecutive patients were included. The objective response rate (ORR) was 44.5950.2-49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95.9-9.5; 599 events) and 17.2 months (955.3-22.3; 598 censored patients), respectively. ECOG-PS ≥ 2 (p textless 0.0001) and bone metastases (p = 0.0003) were confirmed to be independent predictors of a worse ORR. Former smokers (p = 0.0002), but not current smokers (p = 0.0532) were confirmed to have a significantly prolonged PFS compared to never smokers at multivariate analysis. ECOG-PS (p textless 0.0001), bone metastases (p textless 0.0001) and liver metastases (p textless 0.0001) were also confirmed to be independent predictors of a worse PFS. Previous palliative RT was significantly related to a shortened OS (p = 0.0104), while previous non-palliative RT was significantly related to a prolonged OS (p = 0.0033). Former smokers (p = 0.0131), but not current smokers (p = 0.3433) were confirmed to have a significantly prolonged OS compared to never smokers. ECOG-PS (p textless 0.0001), bone metastases (p textless 0.0001) and liver metastases (p textless 0.0001) were also confirmed to be independent predictors of a shortened OS. A PD-L1 expression of ≥ 90 as assessed by recursive partitioning, was associated with significantly higher ORR (p = 0.0204), and longer and OS (p = 0.0346) at multivariable analysis. CONCLUSION: Pembrolizumab was effective in a large cohort of NSCLC patients treated outside of clinical trials. Questions regarding the effectiveness in clinical subgroups, such as patients with poorer PS and with liver/bone metastases, still remain to be addressed. We confirmed that the absence of tobacco exposure, and the presence of bone and liver metastasis are associated with worse clinical outcomes to pembrolizumab. Increasing levels of PD-L1 expression may help identifying a subset of patients who derive a greater benefit from pembrolizumab monotherapy.

M3 - Article

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

IS - 11

ER -