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 journalArticlepeer-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.
Original languageEnglish
Pages (from-to)2209-2221
JournalCancer Immunol. Immunother.
Volume69
Issue number11
DOIs
Publication statusPublished - Nov 2020

Keywords

  • Bone metastases
  • Liver metastases
  • PD-L1
  • Performance status
  • Radiotherapy
  • Smoking status

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