Sistematični pregled in meta-analiza izidov zdravljenja z zaviralci imunskih kontrolnih točk v prvi liniji zdravljenja razsejanega nedrobnoceličnega raka pljuč v opazovalnih raziskavah

Kitak, Tajda (author), Knez, Lea (mentor), Locatelli, Igor (comentor)

Uvod: Rak pljuč je eden najpogosteje identificiranih rakov na svetu. Umrljivost zaradi raka pljuč ostaja visoka in na leto predstavlja 18% vseh smrti zaradi raka. Njegova pogostejša oblika je nedrobnocelični rak pljuč (NDRP), za katerega so za zdravljenje od leta 2015 naprej na voljo zaviralci imunskih kontrolnih točk (ZIKT), ki so občutno izboljšali preživetja bolnikov. Metode dela: Izvedli smo sistematični pregled literature opazovalnih raziskav zdravljenja NDRP z ZIKT, v monoterapiji (mono-IT) ali v kombinaciji s kemoterapijo (KT-IT), v prvi liniji zdravljenja. Pregled literature smo izvedli po smernicah PRISMA 2020. Iskali smo po bazi podatkov Medline s pomočjo iskalnika PubMed, za katerega smo razvili iskalni profil. Iskali smo študije, izvedene med letom 2015 in 31.8.2022. Študije smo izbirali na podlagi vključitvenih in izključitvenih kriterijev in jih razvrstili glede na vrsto zdravljenja. Nato smo iz vključenih študij izpisali izhodiščne značilnosti bolnikov in podatke učinkovitosti zdravljenja ter te statistično ovrednotili v programu R. Rezultate učinkovitosti smo statistično in opisno primerjali še z rezultati registracijskih randomiziranih kliničnih raziskav (RCT). Rezultati: V analizo smo vključili 49 opazovalnih raziskav zdravljenja z mono-IT in 7 opazovalnih raziskav zdravljenja s KT-IT. Značilnosti bolnikov so se v opazovalnih raziskavah razlikovale od RCT predvsem v deležu vključenih bolnikov s stanjem telesne zmogljivosti ⡥2 (18,9 % pri zdravljenju z mono-IT in 8,9 % pri zdravljenju s KT-IT), ker so ti iz RCT izvzeti, in deležu vključenih nekadilcev (10,6 % v primerjavi z 8,1 % pri mono-IT, 22,9 % v primerjavi s 13,1 % pri KT-IT). Bolniki, zdravljeni z mono-IT so bili starejši od bolnikov, vključenih v RCT (mediana starosti 70 v primerjavi s 63). V skupini opazovalnih raziskav zdravljenja z mono-IT je skupna mediana celokupnega preživetja (OS) znašala 17,07 meseca, skupna mediana preživetja brez napredovanja bolezni (PFS) 7,44 meseca, skupen celokupen odgovor na zdravljenje (ORR) 44 % in skupen 1-letni OS 59 %. V skupini opazovalnih raziskav zdravljenja bolnikov s KT-IT je skupna mediana OS znašala 20,36 meseca, skupna mediana PFS 8,26 meseca in skupen ORR 52 %. Podatki učinkovitosti so za opazovalne raziskave zelo heterogeni, prav tako se vključeni bolniki po značilnostih razlikujejo od bolnikov, vključenih v raziskave RCT. Vseeno se učinkovitost zdravljenja za opazovalne raziskave v primerjavi z registracijskimi raziskavami RCT ni statistično značilno razlikovala za izida PFS in ORR pri zdravljenju z mono-IT ali KT-IT, ter OS pri zdravljenju s KT-IT. Statistično značilna je bila razlika za izid OS v skupini zdravljenja z mono-IT, vendar zaradi majhnega vzorca vključenih raziskav RCT ne moremo narediti zaključka.

• Language: Slovenian
• Keywords: zaviralci imunskih kontrolnih točk, sistematični pregled, meta-analiza, opazovalne raziskave, razsejan nedrobnocelični rak pljuč, prva linija zdravljenja
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2023
• PID: 20.500.12556/RUL-147318
• Publication date in RUL: 30.06.2023

Secondary language

• Language: English
• Title: Systematic review and meta-analysis of observational studies evaluating treatment outcomes in patients with metastatic non-small-cell lung cancer on first-line immune checkpoint inhibitors therapy

Abstract

Introduction: Lung cancer is one of the most common cancers in the world. Mortality due to lung cancer remains high, accounting for 18% of all cancer-related deaths annually. Its most common form is non-small cell lung cancer, for which treatment with immune checkpoint inhibitors (ICIs) has been introduced in 2015, significantly improving patient survival. Methods: We conducted a systematic review of observational studies describing the outcomes of non-small cell lung cancer patients, treated with ICIs in monotherapy (mono-IT) or in combination with chemotherapy (CT-IT) in the first-line setting. The literature review was performed following the PRISMA 2020 guidelines. We searched the Medline database using the PubMed search engine, for which we developed a search profile. We searched for studies conducted between the year 2015 and August 31, 2022. Studies were selected based on inclusion and exclusion criteria and categorized according to the type of treatment used. For the included studies, we extracted baseline patients' characteristics and treatment's effectiveness, which were further statistically evaluated using the R software. The effectiveness results were also statistically compared with those of registrational randomized controlled trials (RCT). Results: We included 49 observational studies on mono-IT and 7 observational studies on CT-IT treatment. Patients' characteristics in observational studies differed from RCTs primarily in the proportion of patients with performance status ⡥2 (18,9% in mono-IT treatment and 8,9% in CT-IT treatment) because these patients were excluded from RCTs, and the proportion of included non-smokers (10,6% compared to 8,1% in mono-IT, 22,9% compared to 13,1% in CT-IT). Patients in mono-IT treatment were older than those in RCTs (median age 70 compared to 63). In observational studies of mono-IT treatment, the pooled median overall survival (OS) was 17.07 months, pooled median progression-free survival (PFS) was 7.44 months, pooled overall response rate (ORR) was 44%, and pooled 1-year OS was 59%. In observational studies of CT-IT treatment, the pooled median OS was 20.36 months, pooled median PFS was 8.26 months, and pooled ORR was 52%. The efficacy data are highly heterogeneous for observational studies, and the included patients also differ in characteristics from the patients included in RCTs. However, the treatment efficacy did not statistically significantly differ between observational studies and registrational RCTs for PFS and ORR in mono-IT or KT-IT treatment, and also OS in KT-IT treatment. The difference was statistically significant for OS in mono-IT treatment, but because of the small sample of included RCT studies, the conclusion cannot be drawn.

• Keywords: immune checkpoint inhibitors, systematic review, meta-analysis, observational studies, metastatic non-small-cell lung cancer, first-line treatment