Several clinical studies have evaluated the efficacy and tolerability of treatment with immune checkpoint inhibitors in patients with advanced stage non-small cell lung cancer. However, there are still many uncertainties regarding the selection of the patients who could benefit the most from this treatment. In a context in which there is a slow but constant improvement in the prognosis of a disease traditionally considered poor in the short term, the weight of those variables, above all "clinical" ones, linked to the patient and his non-oncological anamnesis, can contribute to predicting the benefit of treatments as well as their potential toxic effects. The present study aims to evaluate in an unselected population the prognostic and predictive weight of different humoral variables (histology and PD-L1 value on tumour biopsy, presence of anemia, LDH value, neutrophil/lymphocyte ratio) and clinical ones (performance status, age, smoking status, type of anemia corrections, disease sites, comorbid burden) in patients with advanced NSCLC candidates to receive immunotherapy according to AIFA indications. A total of 166 patients from two University Hospitals of Pavia were enrolled. The median age of the entire population was 68.5 years. 71% of the patients were male and 29% female. 92% were active smokers or former smokers. About half of the patients (45-18%) had an ECOG PS score of 0, while 43.37% had an ECOG PS score of 1 and 11.45% of 2-3. 25.3% of patients had squamous NSCLC, while 74.7% had non-squamous carcinoma, histotype adenocarcinoma. 27.16% of patients had an immunohistochemical expression of PD-L1 on tumour biopsy <1%, 45.68% between 1 and 49%, 44% ≥ 50%. At the start of immunotherapy treatment, most of the patients (76.51%) presented with stage IV disease. Nivolumab was administered to 50% of patients, pembrolizumab to 34%, atezolizumab to less than 4% and durvalumab to 12% of patients. In most cases, patients received immunotherapy treatment in the 2nd (57.23%) or 3rd (13.86%) line of treatment. About 50% of patients had anemia at the start of treatment and in most cases the cause of the anemia was the underlying chronic disease. Concerning the sites of disease of interest, about 12% of patients had brain metastases, 11% liver disease, 23% skeletal metastasis, 87% lymph node metastasis and 9% pleural metastasis. The results of this study show that immunotherapy is confirmed to be an effective and well tolerated treatment in an unselected population of patients with advanced non-small cell lung cancer. Our study suggests that some clinical variables are particularly influencing the probability of response to treatment as well as the risk of progression at 6 months and the risk of death at 6 and 12 months. These variables are represented by the patient's performance status, the immunohistochemical expression value of PDL 1 on the tumour piece, the presence of anemia before starting treatment and the LDH values and the neutrophil/lymphocyte ratio. In an era in which research is focusing on prognostic or predictive tumour molecular alterations as well as tumour mutational burden, this study highlights how the clinical characteristics of the patient are still an influential basis for predicting the response and the prognosis to oncological treatments, even more with immune checkpoint inhibitors, in which patient's immune system must guide the response to the treatment itself.
Numerosi studi clinici hanno valutato l’efficacia e la tollerabilità del trattamento con inibitori dei checkpoint immunitari nei pazienti affetti da tumore del polmone non a piccole cellule in fase avanzata. Esistono, tuttavia, ancora molte incertezze in merito alla selezione del paziente che potrebbe trarre il maggiore beneficio da questo trattamento. In un contesto in cui si assiste ad un lento ma costante miglioramento della prognosi di una malattia tradizionalmente considerata infausta nel breve termine, si accresce il peso di quelle variabili, innanzitutto “cliniche”, legate al paziente e alla sua anamnesi non oncologica, che possono contribuire alla predizione del beneficio dei trattamenti così come dei loro potenziali effetti tossici. Il presente studio si propone di valutare in una popolazione non selezionata il peso prognostico e predittivo di diverse variabili umorali (istologia e valore di PD-L1 su pezzo tumorale, presenza di anemia, valore di LDH, rapporto neutrofili/linfociti) e cliniche (performance status, età, stato di fumatore, tipo di correzioni dell’anemia, sedi di malattia, carico di comorbidità) in pazienti affetti da NSCLC avanzato candidati a immunoterapia secondo indicazioni AIFA. Sono stati arruolati un totale di 166 pazienti provenienti da due Ospedali universitari di Pavia. L'età mediana dell'intera popolazione era di 68.5 anni. Il 71% dei pazienti erano maschi e il 29% femmine. Il 92% erano fumatori attivi o ex fumatori. Circa la metà dei pazienti (45-18%) aveva un punteggio ECOG PS pari a 0, mentre il 43.37% aveva un punteggio ECOG PS di 1 e l’11.45% di 2-3. Il 25.3% dei pazienti erano affetti da NSCLC squamoso, mentre il 74.7% avevano un carcinoma non squamoso, istotipo adenocarcinoma. Il 27.16% dei pazienti aveva un’espressione immunoistochimica su tessuto tumorale di PD-L1 < 1%, il 45.68% tra 1 e il 49%, il 44% ≥ al 50%. All’avvio del trattamento immunoterapico, la maggior parte dei pazienti (76.51%) presentava una malattia in stadio IV. Nivolumab è stato somministrato al 50% dei pazienti, pembrolizumab al 34%, atezolizumab a meno del 4% e durvalumab al 12% dei pazienti. Nella maggior parte dei casi, i pazienti hanno ricevuto il trattamento immunoterapico in 2° (57.23%) o 3° (13.86%) linea di trattamento. Poco meno del 50% dei pazienti presentava anemia all’avvio del trattamento e nella maggior parte dei casi la causa dell’anemia era rappresentato dalla malattia cronica sottostante. In merito alle sedi di malattia interessante, circa 12% dei pazienti presentavano metastasi a livello encefalico, 11% malattia a livello epatico, 23% a livello scheletrico, 87% a livello linfonodale e 9% a livello pleurico. I risultati di questa tesi hanno mostrato come l’immunoterapia si conferma un trattamento efficace e ben tollerato in una popolazione non selezionata di pazienti con neoplasia polmonare avanzata non a piccole cellule. Il nostro studio suggerisce come alcune variabili cliniche siano particolarmente influenti sulla probabilità di risposta al trattamento nonché sul rischio di progressione a 6 mesi e sul rischio di morte a 6 e 12 mesi. Tali variabili sono rappresentate dal performance status del paziente, dal valore di espressione immunoistochimica di PDL 1 sul pezzo tumorale, dalla presenza di anemia prima dell’avvio del trattamento e dai valori di LDH e rapporto neutrofili/linfociti su siero. In un’epoca in cui le ricerche si stanno concentrando sulle alterazioni molecolari tumorali prognostiche o predittive di risposta nonché sul carico mutazionale del tumore, questo studio evidenzia come le caratteristiche cliniche del paziente siano ancora una base influente per poter predire la risposta alle cure antiblastiche e la prognosi, a maggior ragione con un trattamento come quello con inibitori dei checkpoint immunitari, in cui è proprio il sistema immunitario del paziente a dover guidare la risposta al trattamento.
FATTORI CLINICI DI EFFICACIA DELLE TERAPIE IMMUNOTERAPICHE ANTI-PD-1/PD-L1 IN PAZIENTI AFFETTI DA CARCINOMA POLMONARE NON A PICCOLE CELLULE IN STADIO AVANZATO: STUDIO REAL-LIFE MULTICENTRICO
QUAQUARINI, ERICA
2021-04-28
Abstract
Several clinical studies have evaluated the efficacy and tolerability of treatment with immune checkpoint inhibitors in patients with advanced stage non-small cell lung cancer. However, there are still many uncertainties regarding the selection of the patients who could benefit the most from this treatment. In a context in which there is a slow but constant improvement in the prognosis of a disease traditionally considered poor in the short term, the weight of those variables, above all "clinical" ones, linked to the patient and his non-oncological anamnesis, can contribute to predicting the benefit of treatments as well as their potential toxic effects. The present study aims to evaluate in an unselected population the prognostic and predictive weight of different humoral variables (histology and PD-L1 value on tumour biopsy, presence of anemia, LDH value, neutrophil/lymphocyte ratio) and clinical ones (performance status, age, smoking status, type of anemia corrections, disease sites, comorbid burden) in patients with advanced NSCLC candidates to receive immunotherapy according to AIFA indications. A total of 166 patients from two University Hospitals of Pavia were enrolled. The median age of the entire population was 68.5 years. 71% of the patients were male and 29% female. 92% were active smokers or former smokers. About half of the patients (45-18%) had an ECOG PS score of 0, while 43.37% had an ECOG PS score of 1 and 11.45% of 2-3. 25.3% of patients had squamous NSCLC, while 74.7% had non-squamous carcinoma, histotype adenocarcinoma. 27.16% of patients had an immunohistochemical expression of PD-L1 on tumour biopsy <1%, 45.68% between 1 and 49%, 44% ≥ 50%. At the start of immunotherapy treatment, most of the patients (76.51%) presented with stage IV disease. Nivolumab was administered to 50% of patients, pembrolizumab to 34%, atezolizumab to less than 4% and durvalumab to 12% of patients. In most cases, patients received immunotherapy treatment in the 2nd (57.23%) or 3rd (13.86%) line of treatment. About 50% of patients had anemia at the start of treatment and in most cases the cause of the anemia was the underlying chronic disease. Concerning the sites of disease of interest, about 12% of patients had brain metastases, 11% liver disease, 23% skeletal metastasis, 87% lymph node metastasis and 9% pleural metastasis. The results of this study show that immunotherapy is confirmed to be an effective and well tolerated treatment in an unselected population of patients with advanced non-small cell lung cancer. Our study suggests that some clinical variables are particularly influencing the probability of response to treatment as well as the risk of progression at 6 months and the risk of death at 6 and 12 months. These variables are represented by the patient's performance status, the immunohistochemical expression value of PDL 1 on the tumour piece, the presence of anemia before starting treatment and the LDH values and the neutrophil/lymphocyte ratio. In an era in which research is focusing on prognostic or predictive tumour molecular alterations as well as tumour mutational burden, this study highlights how the clinical characteristics of the patient are still an influential basis for predicting the response and the prognosis to oncological treatments, even more with immune checkpoint inhibitors, in which patient's immune system must guide the response to the treatment itself.File | Dimensione | Formato | |
---|---|---|---|
TESI PhD Quaquarini Erica.pdf
accesso aperto
Descrizione: FATTORI CLINICI DI EFFICACIA DELLE TERAPIE IMMUNOTERAPICHE ANTI-PD-1/PD-L1 IN PAZIENTI AFFETTI DA CARCINOMA POLMONARE NON A PICCOLE CELLULE IN STADIO AVANZATO: STUDIO REAL-LIFE MULTICENTRICO
Tipologia:
Tesi di dottorato
Dimensione
7.84 MB
Formato
Adobe PDF
|
7.84 MB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.