TY - JOUR
T1 - 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.
AU - Passaro, Antonio
AU - Novello, Silvia
AU - Giannarelli, Diana
AU - Bria, Emilio
AU - Galetta, Domenico
AU - Gelibter, Alain
AU - Reale, Maria Lucia
AU - Carnio, Simona
AU - Vita, Emanuele
AU - Stefani, Alessio
AU - Pizzutilo, Pamela
AU - Stati, Valeria
AU - Attili, Ilaria
AU - de Marinis, Filippo
N1 - Funding Information:
Funding: This work was partially supported by the Italian Ministry of Health with “Ricerca Corrente”, “5 × 1000”.
Funding Information:
Acknowledgments: E.B. is supported by Institutional funds of the Università Cattolica del Sacro Cuore (UCSC-project D1-2019-2020). E.B. is currently supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) under Investigator Grant (IG) No. IG20583.
Funding Information:
Conflicts of Interest: A.P. has received personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli-Lilly, Merck Sharp & Dohme, Jansenn, Novartis, Pfizer, and Roche, outside the submitted work. E.B. received speakers’ and travels’ fee from MSD, Astra-Zeneca, Celgene, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis, and Roche. E.B received consultant’s fee from Roche, Pfizer, and institutional research grants from Astra-Zeneca, Roche, outside the submitted work. F.d.-M. has received honoraria or consulting fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Novartis, Takeda, Xcovery, and Roche, outside the submitted work. D.G. (Domenico Galetta) received speaker’s fee from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli-Lilly, Merck Sharp & Dohme, and Roche, outside the submitted work. The other authors no conflicts to declare. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6/2
Y1 - 2021/6/2
N2 - 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.
AB - 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.
KW - Corticosteroid
KW - Detrimental effect
KW - Immunotherapy
KW - NSCLC
KW - Pleural metastasis
KW - Prognosis
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U2 - 10.3390/cancers13122935
DO - 10.3390/cancers13122935
M3 - Article
AN - SCOPUS:85107614239
VL - 13
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 12
M1 - 2935
ER -