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

A. Cortellini, K. Cannita, M. Tiseo, D.L. Cortinovis, J.G.J.V. Aerts, C. Baldessari, R. Giusti, M.G. Ferrara, E. D'Argento, F. Grossi, A. Guida, R. Berardi, A. Morabito, C. Genova, L. Antonuzzo, F. Mazzoni, A. De Toma, D. Signorelli, A. Gelibter, G. TargatoF. Rastelli, R. Chiari, D. Rocco, S. Gori, M. De Tursi, G. Mansueto, F. Zoratto, M. Filetti, S. Bracarda, F. Citarella, R. Marco, L. Cantini, O. Nigro, S. Buti, G. Minuti, L. Landi, S. Ricciardi, M.R. Migliorino, S. Natalizio, C. Simona, M. De Filippis, G. Metro, V. Adamo, A. Russo, G.P. Spinelli, M. Di Maio, G.L. Banna, A. Friedlaender, A. Addeo, D.J. Pinato, C. Ficorella, G. Porzio

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 - 2021

Keywords

  • Immunotherapy
  • Non-small cell lung cancer
  • PD-L1
  • Pembrolizumab
  • Performance status
  • Post-progression
  • Radiation therapy
  • Radiotherapy
  • corticosteroid
  • pembrolizumab
  • programmed death 1 ligand 1
  • adult
  • aged
  • Article
  • bone metastasis
  • cancer chemotherapy
  • cancer mortality
  • cancer patient
  • cancer radiotherapy
  • central nervous system metastasis
  • clinical outcome
  • cohort analysis
  • comparative study
  • descriptive research
  • doublet chemotherapy
  • drug substitution
  • drug withdrawal
  • ECOG Performance Status
  • female
  • follow up
  • human
  • liver metastasis
  • lung carcinogenesis
  • major clinical study
  • male
  • multicenter study
  • non small cell lung cancer
  • overall survival
  • priority journal
  • protein expression
  • sex difference
  • single drug dose

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