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Published in: Cancer Immunology, Immunotherapy 11/2020

01-11-2020 | NSCLC | Original Article

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

Authors: 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

Published in: Cancer Immunology, Immunotherapy | Issue 11/2020

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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.
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Metadata
Title
Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50%
Authors
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
Publication date
01-11-2020
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 11/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-020-02613-9

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