Early progression in non-small cell lung cancer (Nsclc) with high pd-l1 treated with pembrolizumab in first-line setting: A prognostic scoring system based on clinical features.

Antonio Passaro, Silvia Novello, Diana Giannarelli, Emilio Bria, Domenico Galetta, Alain Gelibter, Maria Lucia Reale, Simona Carnio, Emanuele Vita, Alessio Stefani, Pamela Pizzutilo, Valeria Stati, Ilaria Attili, Filippo de Marinis

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Pembrolizumab is approved in monotherapy for the first-line (1L) of advanced or metastatic NSCLC patients with high PD-L1 (≥50%). Despite a proportion of patients achieve long-term survival, about one-third of patients experience detrimental survival outcomes, including early death, hyperprogression, and fast progression. The impact of clinical factors on early progression (EP) development has not been widely explored. Methods: We designed a retrospective, multicenter study involving five Italian centers, in patients with metastatic NSCLC with PD-L1 ≥ 50%, treated with Pembrolizumab in a 1L setting. EP was defined as a progressive disease within three months from pembrolizumab initiation. Baseline clinical factors of patients with and without EP were collected and analyzed. Logistic regression was performed to identify clinical factors associated with EP and an EP prognostic score was developed based on the logistic model. Results: Overall, 321 out of 336 NSCLC patients treated with 1L pembrolizumab provided all the data for the analysis. EP occurred in 137 (42.7%) patients; the median PFS was 3.8 months (95% CI: 2.9–4.7), and median OS was not reached in the entire study population. Sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), steroids, metastatic sites ≥2, and the presence of liver/pleural metastasis were confirmed as independent factors for EP by multivariate analysis. By combining these factors, we developed an EP prognostic score ranging from 0–13, with three-risk group stratification: 0–2 (good prognosis), 3–6 (intermediate prognosis), and 7–13 (poor prognosis). The area under the curve (AUC) of the model was 0.76 (95% CI: 0.70–0.81). Conclusions: We identified six clinical factors independently associated with EP. We developed a prognostic score model for EP-risk to potentially improve clinical practice and patient selection for 1L pembrolizumab in NSCLC with high PD-L1, in the real-world clinical setting.

Original languageEnglish
Article number2935
JournalCancers
Volume13
Issue number12
DOIs
Publication statusPublished - Jun 2 2021

Keywords

  • Corticosteroid
  • Detrimental effect
  • Immunotherapy
  • NSCLC
  • Pleural metastasis
  • Prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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