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

A. Cortellini; M. Tiseo; G.L. Banna; F. Cappuzzo; J.G.J.V. Aerts; F. Barbieri; R. Giusti; E. Bria; D. Cortinovis; F. Grossi; M.R. Migliorino; D. Galetta; F. Passiglia; D. Santini; R. Berardi; A. Morabito; C. Genova; F. Mazzoni; V. Di Noia; D. Signorelli; A. Tuzi; A. Gelibter; P. Marchetti; M. Macerelli; F. Rastelli; R. Chiari; D. Rocco; S. Gori; M. De Tursi; G. Mansueto; F. Zoratto; M. Santoni; M. Tudini; E. Rijavec; M. Filetti; A. Catino; P. Pizzutilo; L. Sala; F. Citarella; R. Marco; M. Torniai; L. Cantini; G. Targato; V. Sforza; O. Nigro; M.G. Ferrara; E. D’Argento; S. Buti; P. Bordi; L. Antonuzzo; S. Scodes; L. Landi; G. Guaitoli; C. Baldessari; L. Della Gravara; M.G. Dal Bello; R.A. Belderbos; P. Bironzo; S. Carnio; S. Ricciardi; A. Grieco; A. De Toma; C. Proto; A. Friedlaender; O. Cantale; B. Ricciuti; A. Addeo; G. Metro; C. Ficorella; G. Porzio

doi:10.1007/s00262-020-02613-9

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

A. Cortellini, M. Tiseo, G.L. Banna, F. Cappuzzo, J.G.J.V. Aerts, F. Barbieri, R. Giusti, E. Bria, D. Cortinovis, F. Grossi, M.R. Migliorino, D. Galetta, F. Passiglia, D. Santini, R. Berardi, A. Morabito, C. Genova, F. Mazzoni, V. Di Noia, D. SignorelliA. Tuzi, A. Gelibter, P. Marchetti, M. Macerelli, F. Rastelli, R. Chiari, D. Rocco, S. Gori, M. De Tursi, G. Mansueto, F. Zoratto, M. Santoni, M. Tudini, E. Rijavec, M. Filetti, A. Catino, P. Pizzutilo, L. Sala, F. Citarella, R. Marco, M. Torniai, L. Cantini, G. Targato, V. Sforza, O. Nigro, M.G. Ferrara, E. D’Argento, S. Buti, P. Bordi, L. Antonuzzo, S. Scodes, L. Landi, G. Guaitoli, C. Baldessari, L. Della Gravara, M.G. Dal Bello, R.A. Belderbos, P. Bironzo, S. Carnio, S. Ricciardi, A. Grieco, A. De Toma, C. Proto, A. Friedlaender, O. Cantale, B. Ricciuti, A. Addeo, G. Metro, C. Ficorella, G. 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%. Methods: 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%. Results: One thousand and twenty-six consecutive patients were included. The objective response rate (ORR) was 44.5% (95% CI 40.2–49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95% CI 6.9–9.5; 599 events) and 17.2 months (95% CI 15.3–22.3; 598 censored patients), respectively. ECOG-PS ≥ 2 (p <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 <0.0001), bone metastases (p <0.0001) and liver metastases (p <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 <0.0001), bone metastases (p <0.0001) and liver metastases (p <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. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Original language	English
Journal	Cancer Immunol. Immunother.
DOIs	https://doi.org/10.1007/s00262-020-02613-9
Publication status	Published - 2020

Keywords

ONCOLOGIA
STUDIO CLINICO
RIS

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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 Immunol. Immunother.. https://doi.org/10.1007/s00262-020-02613-9

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50%. / 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.; 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, M.G.; D’Argento, E.; Buti, S.; Bordi, P.; Antonuzzo, L.; Scodes, S.; Landi, L.; Guaitoli, G.; Baldessari, C.; Della Gravara, L.; Dal Bello, M.G.; Belderbos, R.A.; 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.

In: Cancer Immunol. Immunother., 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 Immunol. Immunother.. https://doi.org/10.1007/s00262-020-02613-9

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. ; 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, M.G. ; D’Argento, E. ; Buti, S. ; Bordi, P. ; Antonuzzo, L. ; Scodes, S. ; Landi, L. ; Guaitoli, G. ; Baldessari, C. ; Della Gravara, L. ; Dal Bello, M.G. ; Belderbos, R.A. ; 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. / Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50%. In: Cancer Immunol. Immunother. 2020.

@article{e9fe192c26394218913a8d7e89c3b8f4,

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%. Methods: 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%. Results: One thousand and twenty-six consecutive patients were included. The objective response rate (ORR) was 44.5% (95% CI 40.2–49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95% CI 6.9–9.5; 599 events) and 17.2 months (95% CI 15.3–22.3; 598 censored patients), respectively. ECOG-PS ≥ 2 (p <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 <0.0001), bone metastases (p <0.0001) and liver metastases (p <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 <0.0001), bone metastases (p <0.0001) and liver metastases (p <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. {\textcopyright} 2020, Springer-Verlag GmbH Germany, part of Springer Nature.",

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author = "A. Cortellini and M. Tiseo and G.L. Banna and F. Cappuzzo and J.G.J.V. Aerts and F. Barbieri and R. Giusti and E. Bria and D. Cortinovis and F. Grossi and M.R. Migliorino and D. Galetta and F. Passiglia and D. Santini and R. Berardi and A. Morabito and C. Genova and F. Mazzoni and {Di Noia}, V. and D. Signorelli and A. Tuzi and A. Gelibter and P. Marchetti and M. Macerelli and F. Rastelli and R. Chiari and D. Rocco and S. Gori and {De Tursi}, M. and G. Mansueto and F. Zoratto and M. Santoni and M. Tudini and E. Rijavec and M. Filetti and A. Catino and P. Pizzutilo and L. Sala and F. Citarella and R. Marco and M. Torniai and L. Cantini and G. Targato and V. Sforza and O. Nigro and M.G. Ferrara and E. D{\textquoteright}Argento and S. Buti and P. Bordi and L. Antonuzzo and S. Scodes and L. Landi and G. Guaitoli and C. Baldessari and {Della Gravara}, L. and {Dal Bello}, M.G. and R.A. Belderbos and P. Bironzo and S. Carnio and S. Ricciardi and A. Grieco and {De Toma}, A. and C. Proto and A. Friedlaender and O. Cantale and B. Ricciuti and A. Addeo and G. Metro and C. Ficorella and G. Porzio",

year = "2020",

doi = "10.1007/s00262-020-02613-9",

language = "English",

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TY - JOUR

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

AU - Cortellini, A.

AU - Tiseo, M.

AU - Banna, G.L.

AU - Cappuzzo, F.

AU - Aerts, J.G.J.V.

AU - Barbieri, F.

AU - Giusti, R.

AU - Bria, E.

AU - Cortinovis, D.

AU - Grossi, F.

AU - Migliorino, M.R.

AU - Galetta, D.

AU - Passiglia, F.

AU - Santini, D.

AU - Berardi, R.

AU - Morabito, A.

AU - Genova, C.

AU - Mazzoni, F.

AU - Di Noia, V.

AU - Signorelli, D.

AU - Tuzi, A.

AU - Gelibter, A.

AU - Marchetti, P.

AU - Macerelli, M.

AU - Rastelli, F.

AU - Chiari, R.

AU - Rocco, D.

AU - Gori, S.

AU - De Tursi, M.

AU - Mansueto, G.

AU - Zoratto, F.

AU - Santoni, M.

AU - Tudini, M.

AU - Rijavec, E.

AU - Filetti, M.

AU - Catino, A.

AU - Pizzutilo, P.

AU - Sala, L.

AU - Citarella, F.

AU - Marco, R.

AU - Torniai, M.

AU - Cantini, L.

AU - Targato, G.

AU - Sforza, V.

AU - Nigro, O.

AU - Ferrara, M.G.

AU - D’Argento, E.

AU - Buti, S.

AU - Bordi, P.

AU - Antonuzzo, L.

AU - Scodes, S.

AU - Landi, L.

AU - Guaitoli, G.

AU - Baldessari, C.

AU - Della Gravara, L.

AU - Dal Bello, M.G.

AU - Belderbos, R.A.

AU - Bironzo, P.

AU - Carnio, S.

AU - Ricciardi, S.

AU - Grieco, A.

AU - De Toma, A.

AU - Proto, C.

AU - Friedlaender, A.

AU - Cantale, O.

AU - Ricciuti, B.

AU - Addeo, A.

AU - Metro, G.

AU - Ficorella, C.

AU - Porzio, G.

PY - 2020

Y1 - 2020

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%. Methods: 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%. Results: One thousand and twenty-six consecutive patients were included. The objective response rate (ORR) was 44.5% (95% CI 40.2–49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95% CI 6.9–9.5; 599 events) and 17.2 months (95% CI 15.3–22.3; 598 censored patients), respectively. ECOG-PS ≥ 2 (p <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 <0.0001), bone metastases (p <0.0001) and liver metastases (p <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 <0.0001), bone metastases (p <0.0001) and liver metastases (p <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. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

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%. Methods: 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%. Results: One thousand and twenty-six consecutive patients were included. The objective response rate (ORR) was 44.5% (95% CI 40.2–49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95% CI 6.9–9.5; 599 events) and 17.2 months (95% CI 15.3–22.3; 598 censored patients), respectively. ECOG-PS ≥ 2 (p <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 <0.0001), bone metastases (p <0.0001) and liver metastases (p <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 <0.0001), bone metastases (p <0.0001) and liver metastases (p <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. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

KW - ONCOLOGIA

KW - STUDIO CLINICO

KW - RIS

U2 - 10.1007/s00262-020-02613-9

DO - 10.1007/s00262-020-02613-9

M3 - Article

JO - Cancer Immunol. Immunother.

JF - Cancer Immunol. Immunother.

SN - 0340-7004

ER -