Nov 2021: Pembrolizumab (Keytruda, Merck) in conjunction with chemotherapy, with or without bevacizumab, has been approved by the Food and Drug Administration for patients with persistent, recurrent, or metastatic cervical cancer whose tumours express PD-L1 (CPS 1), as determined by an FDA-approved test.
FDA je tudi redno odobrila pembrolizumab kot enkratno zdravljenje za bolnike s ponavljajočim se ali metastatskim rakom materničnega vratu, pri katerih je bolezen napredovala med ali po kemoterapiji in katerih tumorji izražajo PD-L1 (CPS 1), kot je bilo ugotovljeno s testom, ki ga je odobrila FDA. FDA je odobrila pospešeno odobritev te indikacije junija 2018, skupaj s spremljajočim testom, PD-L1 IHC 22C3 pharmDx (Dako North America Inc.).
Pembrolizumab with paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab, was studied in KEYNOTE-826 (NCT03635567), a multicenter, randomised, double-blind, placebo-controlled trial. The experiment involved 617 patients who had not been treated with chemotherapy and had chronic, recurring, or first-line metastatic rak materničnega vratu. Patients were enrolled regardless of whether or whether they had PD-L1 expression. Pembrolizumab 200 mg with chemotherapy with or without bevacizumab or placebo plus chemotherapy with or without bevacizumab were randomly assigned (1:1) to one of two treatment groups. Pembrolizumab was given until disease progression, intolerable toxicity, or 24 months had passed from the start of the study.
Splošno preživetje (OS) in preživetje brez napredovanja (PFS) sta bili ključni meritvi izida učinkovitosti, ki ju je raziskovalec ocenil z uporabo RECIST v1.1, ki je bil prilagojen tako, da sledi največ 10 ciljnim lezijam in največ 5 ciljnim lezijam. na organ. ORR in dolžina reakcije sta bila uporabljena tudi kot dodatna merila izida (DoR). Mediana OS v kraku s pembrolizumabom ni bila dosežena (95-odstotni IZ: 19.8, NR) in je bila 16.3 meseca (95-odstotni IZ: 14.5, 19.4) v skupini s placebom (HR 0.64; 95-odstotni IZ: 0.50, 0.81; 1- stranska p-vrednost = 0.0001) za bolnike s tumorji, ki izražajo PD-L1 (CPS 1, N=548). Mediana PFS v kraku s pembrolizumabom je bila 10.4 meseca (95-odstotni IZ: 9.7, 12.3), medtem ko je bila v skupini s placebom 8.2 meseca (95-odstotni IZ: 6.3, 8.5) (HR 0.62; 95-odstotni IZ: 0.50, 0.77; 1 stranska p-vrednost 0.0001). V kraku s pembrolizumabom in placebom so bile objektivne stopnje odziva 68 odstotkov (95 odstotkov IZ: 62, 74) oziroma 50 odstotkov (95 odstotkov IZ: 44, 56) s mediano DoR 18.0 in 10.4 meseca.
Pembrolizumab, chemotherapy, and bevacizumab were associated with peripheral neuropathy, alopecia, anaemia, fatigue/asthenia, nausea, neutropenia, diarrhoea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism, and decreased appetite in 20 percent of patients.
Pembrolizumab se daje v odmerku 200 mg vsake 3 tedne ali 400 mg vsakih 6 tednov, dokler ne pride do napredovanja bolezni ali nesprejemljive toksičnosti, ki lahko traja do 24 mesecev.
