Raziskava možnosti racionalizacije režima odmerjanja pembrolizumaba pri zdravljenju napredovalega nedrobnoceličnega raka pljuč

Rus, Zala (author), Knez, Lea (mentor), Janžič, Urška (comentor)

Pembrolizumab je monoklonsko protitelo, ki z vezavo na imunske kontrolne točke ponovno aktivira zavrt imunski sistem in pomaga telesu prepoznati, napasti in uničiti rakave celice. V začetnih kliničnih študijah je bil pembrolizumab odmerjan glede na bolnikovo telesno maso, in sicer 2 mg/kg telesne mase vsake 3 tedne. V kasnejših kliničnih študijah je bil pembrolizumab odmerjan v fiksnem odmerku, neprilagojenem na telesno maso, in sicer 200 mg vsake 3 tedne oziroma 400 mg vsakih 6 tednov. Večina onkoloških bolnikov v naši raziskavi tehta manj kot 100 kg, zato bi glede na svojo telesno maso lahko prejeli odmerke pembrolizumaba, ki so nižji od registriranega odmerka 200 mg vsake 3 tedne. Namen magistrske naloge je opisati zdravljenje, režim odmerjanja in celokupno porabo pembrolizumaba, kot so ga prejeli bolniki v prvi liniji zdravljenja napredovalega nedrobnoceličnega raka pljuč, zdravljeni na Kliniki Golnik, ter oceniti možnosti zmanjšanja porabe zdravila ob odmerjanju pembrolizumaba na telesno maso. V opazovalno retrospektivno raziskavo smo vključili 124 bolnikov z napredovalim nedrobnoceličnim rakom pljuč, ki so na Kliniki Golnik med avgustom 2017 in decembrom 2021 pričeli zdravljenje s pembrolizumabom v prvi liniji. Podatke o bolnikih smo pridobili iz bolnišničnega informacijskega sistema BIRPIS in popisov bolnikov. Na podlagi prejetih odmerkov in trajanja zdravljenja s pembrolizumabom smo izračunali odmerek pembrolizumaba vsake 3 tedne ter celokupno porabo pembrolizumaba. To smo naredili za tri režime odmerjanja pembrolizumaba, in sicer za i) zdravljenje s pembrolizumabom, kot so ga bolniki prejeli, ii) zdravljenje s pembrolizumabom ob sledenju registriranemu režimu odmerjanja in iii) zdravljenju s pembrolizumabom ob prilagajanju odmerka telesni masi. Vključenih 124 bolnikov je v povprečju prejelo 8 aplikacij pembrolizumaba v odmerku 200 mg in so se v povprečju zdravili 24 tednov. Tako je bil povprečni preračunan odmerek pembrolizumaba, ki so ga bolniki prejeli, 190 mg vsake 3 tedne. Pri sledenju registriranemu režimu odmerjanja bi bil ta odmerek vedno 200 mg pembrolizumaba vsake 3 tedne, pri prilagajanju odmerka na telesno maso pa v povprečju 146 mg pembrolizumaba vsake 3 tedne. Na kohorti 124 vključenih bolnikov so v klinični praksi celokupno porabili 283.600 mg pembrolizumaba, kar je 44.200 mg pembrolizumaba manj, kot če bi sledili registriranemu režimu odmerjanja. Pri prilagajanju odmerka pembrolizumaba na telesno maso pa bi prihranili še dodatnih 32.400 mg. Z odmerjanjem pembrolizumaba glede na telesno maso, kot je bil prvotno registriran, bi lahko pomembno zmanjšali porabo pembrolizumaba v primerjavi z odmerjanjem s fiksnim odmerkom pembrolizumaba, ki je trenutno registriran režim odmerjanja.

• Language: Slovenian
• Keywords: razsejani nedrobnocelični rak pljuč, pembrolizumab, imunoterapija, podaljšan interval odmerjanja, primerjava stroškov
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2022
• PID: 20.500.12556/RUL-143404
• Publication date in RUL: 20.12.2022

Secondary language

• Language: English
• Title: Evaluation of possible pembrolizumab dosing regimen racionalisation in advanced non-small cell lung cancer

Abstract

Pembrolizumab is a monoclonal antibody that binds to immune checkpoints, reactivates the immune system suppressed by cancer cells, and thus helps the body to recognise, attack and destroy cancer cells. In pivotal clinical studies, pembrolizumab was dosed according to the patient's body weight, at 2 mg/kg body weight every 3 weeks. However, in more recent clinical studies, pembrolizumab was dosed at a fixed dose, regardless of body weight, at 200 mg every 3 weeks or 400 mg every 6 weeks. Since most cancer patients weigh less than 100 kg, most would receive a lower dose than 200 mg if pembrolizumab was dosed according to the body weight. Our study aimed to describe the treatment characteristics, dosing regimen and total consumption of pembrolizumab in patients with advanced non-small lung cancer, treated with first line pembrolizumab at the University Clinic Golnik, and to evaluate the possibility of reducing the consumption of pembrolizumab if dosed according to the body weight. We conducted a retrospective observational study of 124 patients with advanced non-small lung cancer who started first-line treatment with pembrolizumab at the University Clinic Golnik between August 2017 and December 2021. Patient data were obtained from the hospital information system BIRPIS and patient medical records. Based on the number of pembrolizumab doses received and the duration of treatment, the pembrolizumab dose received by patients every 3 weeks and the total pembrolizumab consumption were calculated. This was done for three pembrolizumab dosing regimens: i) pembrolizumab treatment as received by patients, ii) pembrolizumab treatment according to the approved dosing regimen, and iii) pembrolizumab treatment while adjusting the dose according to the body weight. The 124 patients included received an average of 8 administrations of pembrolizumab at a dose of 200 mg and were treated for an average of 24 weeks. Therefore, on average, patients had received 190 mg of pembrolizumab every 3 weeks. If the approved dosing regimen is followed, patients would always receive 200 mg of pembrolizumab every 3 weeks. If the pembrolizumab dose was adjusted according to the body weight, patients would receive an average of 146 mg of pembrolizumab every 3 weeks. In the cohort of 124 enrolled patients, a total of 283,600 mg of pembrolizumab was used. This is 44,200 mg of pembrolizumab less than if the approved dosing regimen was followed. Adjusting the dose of pembrolizumab according to the body weight would have saved an additional 32,400 mg. Dosing pembrolizumab according to the body weight, as initially approved, could significantly reduce the consumption of pembrolizumab compared with fixed-dosing as currently approved.

• Keywords: non-small cell lung cancer, pembrolizumab, immunotherapy, extended dosing interval, cost comparison