Alessandro Russo1, Marco Russano2, Antonio Russo3, Tindara Franchina1, Maria R Migliorino4, Giuseppe Aprile5, Giovanni Mansueto6, Alfredo Berruti7, Alfredo Falcone8, Michele Aieta9, Alain Gelibter10, Sandro Barni11, Michele Maio12, Olga Martelli13, Francesco Pantano2, Daniela Iacono4, Lorenzo Calvetti5, Silvia Quadrini6, Elisa Roca7, Enrico Vasile8, Marco Imperatori9, Mario Occhipinti10, Antonio Galvano3, Fausto Petrelli11, Luana Calabrò12, Giulia Pasquini8, Salvatore Intagliata7, Giuseppina R R Ricciardi1, Giuseppe Tonini2, Daniele Santini2, Vincenzo Adamo14. 1. Medical Oncology Unit A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy. 2. Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy. 3. Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy. 4. Pulmonary Oncology Unit, St. Camillo Forlanini Hospital, Rome, Italy. 5. Department of Oncology, San Bortolo General Hospital, Vicenza, Italy. 6. Medical Oncology Department, General Hospital, Frosinone, Italy. 7. Oncologia Medica, Azienda Ospedaliera Spedali Civili, Brescia, Italy. 8. Unit of Medical Oncology, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy. 9. Division of Medical Oncology, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero Vulture, PZ, Italy. 10. Division of Oncology, Department of Radiological, Oncological and Pathological Science, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy. 11. Medical Oncology Unit, ASST Bergamo Ovest, Treviglio, BG, Italy. 12. Medical Oncology and Immunotherapy, Center for Immuno-oncology, University Hospital of Siena, Siena, Italy. 13. Medical Oncology Unit, San Giovanni Addolorata Hospital, Rome, Italy. 14. Medical Oncology Unit A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy. vadamo@unime.it.
Abstract
INTRODUCTION: Immune checkpoint inhibitors have provided substantial benefit in non-small cell lung cancer (NSCLC) with unprecedented results in terms of survival. However, the identification of reliable predictive biomarkers to these agents is lacking and multiple clinicopathological factors have been evaluated. The aim of this study was to analyze the potential role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) levels in patients with pretreated NSCLC receiving nivolumab. METHODS: This was a retrospective multicenter study involving 14 Italian centers, evaluating the role of some laboratory results in patients with NSCLC treated with nivolumab in the second or later lines of therapy for at least four doses and with a disease re-staging. RESULTS: A total of 187 patients with available pretreatment laboratory results were included. NLR levels below 5 were associated with an improvement in terms of both progression-free survival (PFS) (p = 0.028) and overall survival (OS) (p = 0.001), but not in terms of overall response rate (ORR) or disease control rate (DCR). Moreover, PLR levels below 200 were associated with longer PFS (p = 0.0267) and OS (p = 0.05), as well as higher ORR (p = 0.04) and DCR (p = 0.001). In contrast, LDH levels above the upper normal limit (UNL) were not associated with significant impact on patient outcomes. CONCLUSIONS: Patients with pretreated NSCLC and high pretreatment levels of NLR and PLR may experience inferior outcomes with nivolumab. Therefore, in this subgroup of patients with poor prognosis the use of alternative therapeutic strategies may be a valuable option, especially in programmed cell death ligand 1 (PD-L1)-negative patients and/or in the presence of other additional poor prognostic factors.
INTRODUCTION: Immune checkpoint inhibitors have provided substantial benefit in non-small cell lung cancer (NSCLC) with unprecedented results in terms of survival. However, the identification of reliable predictive biomarkers to these agents is lacking and multiple clinicopathological factors have been evaluated. The aim of this study was to analyze the potential role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) levels in patients with pretreated NSCLC receiving nivolumab. METHODS: This was a retrospective multicenter study involving 14 Italian centers, evaluating the role of some laboratory results in patients with NSCLC treated with nivolumab in the second or later lines of therapy for at least four doses and with a disease re-staging. RESULTS: A total of 187 patients with available pretreatment laboratory results were included. NLR levels below 5 were associated with an improvement in terms of both progression-free survival (PFS) (p = 0.028) and overall survival (OS) (p = 0.001), but not in terms of overall response rate (ORR) or disease control rate (DCR). Moreover, PLR levels below 200 were associated with longer PFS (p = 0.0267) and OS (p = 0.05), as well as higher ORR (p = 0.04) and DCR (p = 0.001). In contrast, LDH levels above the upper normal limit (UNL) were not associated with significant impact on patient outcomes. CONCLUSIONS:Patients with pretreated NSCLC and high pretreatment levels of NLR and PLR may experience inferior outcomes with nivolumab. Therefore, in this subgroup of patients with poor prognosis the use of alternative therapeutic strategies may be a valuable option, especially in programmed cell death ligand 1 (PD-L1)-negative patients and/or in the presence of other additional poor prognostic factors.
Authors: Diego L Kaen; Nicolas Minatta; Alessandro Russo; Umberto Malapelle; Diego de Miguel-Pérez; Christian Rolfo Journal: Adv Exp Med Biol Date: 2021 Impact factor: 2.622