Učinkovitost in varnost imunoterapije pri bolnikih z napredovalim nedrobnoceličnim pljučnim rakom zdravljenih v drugi liniji na Kliniki Golnik

Ljepojević, Tamara (author), Knez, Lea (mentor), Pelicon, Veronika (co-mentor)

Pljučni rak je ena izmed najpogostejših oblik raka na svetu in vodilni vzrok smrti po celem svetu. Nedrobnocelični pljučni rak (NDRP) je najpogostejša oblika pljučnega raka; ker pa je skoraj polovica diagnosticirana v napredovali fazi bolezni, je celokupno preživetje teh bolnikov zelo skromno in 5-letno preživetje je manj kot 10 %. V zadnjih letih se je uveljavila terapija z zaviralci imunskih kontrolnih točk (ZKT). Z našo raziskavo smo želeli ugotoviti učinkovitost in varnost ZKT v monoterapiji v drugi liniji zdravljenja napredovalega NDRP pri bolnikih, zdravljenih na Kliniki Golnik v okviru rutinske klinične prakse. Vključili smo 87 bolnikov z napredovalim NDRP brez gonilnih tarčnih sprememb EGFR (angl. epidermal growth factor receptor), ALK (angl. anaplastic lymphoma kinase) in ROS1 (angl. ROS Proto-Oncogene 1, Receptor Tyrosine Kinase), ki so na Kliniki Golnik od julija 2015 do aprila 2022 v okviru rutinske klinične prakse prejeli ZKT (pembrolizumab, atezolizumab ali nivolumab) v drugi liniji zdravljenja. V sklopu analize smo ocenili srednji čas preživetja (angl. median overall survival; mOS), čas zdravljenja (angl. duration of treatment; DOT) ter celokupno preživetje po enem in dveh letih. Naredili smo tudi univariantno in multivariantno analizo, da smo preverili, katere značilnosti bolnika in bolezni vplivajo na izid zdravljenja. Mediana spremljanja bolnikov je bila 38,6 meseca. Vključeni bolniki so bili starejši (mediana starost 65 let); 62 % (54/87) je bila moških in 13 % (11/87) bolnikov je imelo slabši status telesne zmogljivosti (PS ⡥ 2). Bolniki so prejeli atezolizumab 37 % (32/87), nivolumab 33 % (29/87) ali pembrolizumab 30 % (26/87). mDOT je bila 5,0 mesecev (95 % IZ, 2,4 - 8,2), mOS pa 11,8 mesecev (95 % IZ, 10,0-13,6). Enoletno preživetje bolnikov je bilo 53 % in dvoletno preživetje 23 %. Neželeni učinki vseh stopenj so bili prisotni pri 91 % (77/87) bolnikov, hujši (stopnje 3-4) pa pri 17 % (15/17) bolnikov. Smrti zaradi ZKT ni bilo. Izidi učinkovitosti zdravljenja z ZKT pri vključenih bolnikih z mOS 11,8 mesecev so primerljivi s štirimi registracijskimi raziskavami, kjer so mOS bile v intervalu od 9,2 meseca do 12,2 meseca. Pojavnost neželenih učinkov v naši raziskavi se giblje v podobnem obsegu kot v kliničnih raziskavah, z nekoliko višjim izražanjem v primerjavi z opazovalnimi študijami.

• Language: Slovenian
• Keywords: napredovali nedrobnocelični rak pljuč, imunoterapija, zaviralci imunskih kontrolnih točk, druga linija, monoterapija, retrospektivna opazovalna raziskava
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2023
• PID: 20.500.12556/RUL-152382
• Publication date in RUL: 23.11.2023

Secondary language

• Language: English
• Title: Effectivness and safety of immunotherapy in patients with advanced non-small cell lung cancer in second line treatment at the University Clinic Golnik

Abstract

Lung cancer is one of the most common forms of cancer worldwide and a leading cause of death globally. Non-small cell lung cancer (NSCLC) is the most frequent type of lung cancer. However, since nearly half of the cases are diagnosed in an advanced stage of the disease, the overall survival rate for these patients is very modest, amounting to less than 10% surviving for 5 years. In recent years, therapy with immune checkpoint inhibitors (ICI) has been introduced. With our study, we aimed to determine the effectiveness and safety of ICI monotherapy in the second-line treatment of advanced non-small cell lung cancer (NSCLC) in patients treated at the Golnik Clinic within routine clinical practice. We included 87 patients with advanced NSCLC, without driver target alterations in EGFR, ALK, and ROS1, who received ICI (pembrolizumab, atezolizumab, or nivolumab) as second-line treatment at the University Clinic Golnik from July 2015 to April 2022 within routine clinical practice. As part of the analysis, we evaluated the median overall survival (mOS), duration of treatment (DOT), and overall survival at one and two years. Univariate and multivariate analyses were also conducted to examine which prognostic and predictive patient characteristics are associated with treatment outcomes. The included patients were older (median age 65 years). 62% (54/87) were male and 13% (11/87) of patients had a poorer performance status (PS ⡥ 2). Patients received atezolizumab 37% (32/87), nivolumab 33% (29/87), or pembrolizumab 30% (32/87). The median duration of treatment (mDOT) was 5.0 months (95% CI, 2.4-8.2), and the median overall survival (mOS) was 11.8 months (95% CI, 10.0-13.6). One-year survival of patients was 53%, and two-year survival was 23%. Adverse events of all grades were present in 91% (77/87) of patients, with severe (grades 3-4) events in 17% (15/87) of patients. There were no deaths attributed to immune checkpoint inhibitor therapy. The effectiveness of ICI in our collective of patients is comparable to the outcomes in four registration studies where mOS ranged from 9.2 months to 12.2 months. The incidence of adverse events in our study falls within the range reported in clinical trials with a slightly higher occurrence compared to observational studies.

• Keywords: advanced non-small cell lung cancer, immunotherapy, immune checkpoint inhibitors, second-line, monotherapy, retrospective observational study.