Clinicopathologic correlates of pembrolizumab efficacy in patients with advanced NSCLC and a PD-L1 expression of ≥ 50%
Authors: Cortellini Alessio , Tiseo Marcello , Banna Giuseppe L , Cappuzzo Federico , Aerts Joachim GJV , 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 , Noia Vincenzo Di , 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 , Gravara Luigi Della , 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 
Published: April 2020

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 study aimed at evaluating the clinicopathologic correlates of pembrolizumab efficacy in patients with treatment-naïve NSCLC and a PD-L1 TPS ≥ 50%.

Results

1026 consecutive patients were included. 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.

Conclusions

pembrolizumab was effective in a large cohort of NSCLC patients treated outside of clinical trials. 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.