Post-progression outcomes of NSCLC patients with PD-L1 expression ≥ 50% receiving first-line single-agent pembrolizumab in a large multicentre real-world study

Alessio Cortellini, Katia Cannita, Marcello Tiseo, Diego L. Cortinovis, Joachim G.J.V. Aerts, Cinzia Baldessari, Raffaele Giusti, Miriam G. Ferrara, Ettore D'Argento, Francesco Grossi, Annalisa Guida, Rossana Berardi, Alessandro Morabito, Carlo Genova, Lorenzo Antonuzzo, Francesca Mazzoni, Alessandro De Toma, Diego Signorelli, Alain Gelibter, Giada TargatoFrancesca Rastelli, Rita Chiari, Danilo Rocco, Stefania Gori, Michele De Tursi, Giovanni Mansueto, Federica Zoratto, Marco Filetti, Sergio Bracarda, Fabrizio Citarella, Russano Marco, Luca Cantini, Olga Nigro, Sebastiano Buti, Gabriele Minuti, Lorenza Landi, Serena Ricciardi, Maria R. Migliorino, Salvatore Natalizio, Carnio Simona, Marco De Filippis, Giulio Metro, Vincenzo Adamo, Alessandro Russo, Gian P. Spinelli, Massimo Di Maio, Giuseppe L. Banna, Alex Friedlaender, Alfredo Addeo, David J. Pinato

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Treatment sequencing with first-line immunotherapy, followed by second-line chemotherapy, is still a viable option for NSCLC patients with PD-L1 expression ≥50%. Methods: We evaluated post-progression treatment pathways in a large real-world cohort of metastatic NSCLC patients with PD-L1 expression ≥ 50% treated with first-line pembrolizumab monotherapy. Results: Overall, 974 patients were included. With a median follow-up of 22.7 months (95%CI: 21.6–38.2), the median overall survival (OS) of the entire population was 15.8 months (95%CI: 13.5–17.5; 548 events). At the data cutoff, among the 678 patients who experienced disease progression, 379 (55.9%) had not received any further treatment, and 359 patients (52.9%) had died. Patients who did not receive post-progression therapies were older (p = 0.0011), with a worse ECOG-PS (p < 0.0001) and were on corticosteroids prior to pembrolizumab (p = 0.0024). At disease progression, 198 patients (29.2%) received a switched approach and 101 (14.9%) received pembrolizumab ByPD either alone (64 [9.4%]) or in combination with local ablative treatments (37 [5.5%]) (LATs). After a random-case control matching according to ECOG-PS, CNS metastases, bone metastases, and (previous) best response to pembrolizumab, patients receiving pembrolizumab ByPD plus LATs were confirmed to have a significantly longer post-progression OS compared to patients receiving pembrolizumab ByPD alone 13.9 months versus 7.8 months (p = 0.0179) 241 patients (35.5%) among the 678 who had experienced PD, received a second-line systemic treatment (regardless of previous treatment beyond PD). As compared to first-line treatment commencement, patients’ features at the moment of second-line initiation showed a significantly higher proportion of patients aged under 70 years (p = 0.0244), with a poorer ECOG-PS (p < 0.0001) and having CNS (p = 0.0001), bone (p = 0.0266) and liver metastases (p = 0.0148). Conclusions: In the real-world scenario NSCLC patients with PD-L1 expression ≥50% treated with first-line single-agent pembrolizumab achieve worse outcomes as compared to the Keynote-024 trial. Poor post-progression outcomes are major determinants of the global results that should be considered when counselling patients for first-line treatment choices.

Original languageEnglish
Pages (from-to)24-35
Number of pages12
JournalEuropean Journal of Cancer
Volume148
DOIs
Publication statusPublished - May 2021

Keywords

  • Immunotherapy
  • Non-small cell lung cancer
  • PD-L1
  • Pembrolizumab
  • Performance status
  • Post-progression
  • Radiation therapy
  • Radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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