Zie ook onder alvleesklierkanker voor gerelateerde artikelen.

Raadpleeg ook literatuurlijst niet-toxische middelen en behandelingen specifiek bij alvleesklierkanker en galwegkanker van arts-bioloog drs. Engelbert Valstar.

Zie ook dit artikel: https://kanker-actueel.nl/personalised-medicine-op-basis-van-dna-en-rna-mutaties-voor-bv-immuuntherapie-met-anti-pd-en-gerichte-behandelingen-lijkt-voor-galwegenkanker-zeker-zinvol-aldus-overzichtsstudie.html


31 mei 2024: Bron: The Lancet

Wanneer bij patiënten met gevorderde uitgezaaide galwegkanker immuuntherapie met het anti-PD medicijn / checkpointremmer Durvalumab wordt toegevoegd aan de standaard eerstelijns behandeling met gemcitabine plus cisplatine dan geeft dat een verbeterde overall overleving in vergelijking met een placebo ipv Durvalumab. Hoewel het verschil niet echt spectaculair blijkt uit een tussenanalyse, al blijkt dat hoe langer in tijd de durvalumabgroep het steeds beter deed qua overleving. Overall overleving in de durvalumabgroep op 2-jaars meting was 24,9 procent versus 10,4 procent in de placebogroep.

Ook vervolgonderzoek geeft wel een gelijke of betere kwaliteit van leven. Dat blijkt uit een patiëntenvragenlijst gegeven aan de deelnemende patiënten in de dubbelblinde placebo gecontroleerde gerandomiseerde TOPAZ-1 fase III-studie. Dus in de klinische praktijk werd deze behandeling als verbetering van kwaliteit van leven ervaren.

In dit artikel "Durvalumab toegevoegd aan gemcitabine en cisplatine als eerstelijnsbehandeling van het gevorderd galwegcarcinoom" wordt uitgebreid beschreven wat de resultaten zijn van de TOPAZ-1 fase III-studie.

Overlevingsresultaten
:

OS - Overall overleving was statistisch significant langer in de durvalumabgroep dan in de placebogroep (HR: 0,80 [95%BI: 0,66-0,97]; p = 0,021).
De mediane OS - Overall overleving was 12,8 maanden (95%BI: 11,1-14,0) in de durvalumabgroep en 11,5 maanden (95%BI: 10,1-12,5) in de placebogroep.
De geschatte OS - Overall overleving in de durvalumabgroep en in de placebogroep waren respectievelijk 54,1 procent (95%BI: 48,4-59,4) en 48 procent (95%BI: 42,4-53,4) na 1 jaar.
Op 2-jaars meting was deze 24,9 procent (95%BI: 17,9-32,5) en 10,4 procent (95%BI: 4,7-18,8).


De nieuwe publicatie uit The Lancet beschrijft de uitkomsten van de vragenlijst. Hier het abstract. Voor het volledige studierapport moet worden betaald.

ARTICLES| VOLUME 25, ISSUE 5P626-635, MAY 2024

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial


Summary

Background

In the ongoing, randomised, double-blind phase 3 TOPAZ-1 study, durvalumab, a PD-L1 inhibitor, plus gemcitabine and cisplatin was associated with significant improvements in overall survival compared with placebo, gemcitabine, and cisplatin in people with advanced biliary tract cancer at the pre-planned intermin analysis. In this paper, we present patient-reported outcomes from TOPAZ-1.

Methods

In TOPAZ-1 (NCT03875235), participants aged 18 years or older with previously untreated, unresectable, locally advanced, or metastatic biliary tract cancer with an Eastern Cooperative Oncology Group performance status of 0 or 1 and one or more measurable lesions per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) were randomly assigned (1:1) to the durvalumab group or the placebo group using a computer-generated randomisation scheme. Participants received 1500 mg durvalumab or matched placebo intravenously every 3 weeks (on day 1 of the cycle) for up to eight cycles in combination with 1000 mg/m2 gemcitabine and 25 mg/m2 cisplatin intravenously on days 1 and 8 every 3 weeks for up to eight cycles. Thereafter, participants received either durvalumab (1500 mg) or placebo monotherapy intravenously every 4 weeks until disease progression or other discontinuation criteria were met. Randomisation was stratified by disease status (initially unresectable vs recurrent) and primary tumour location (intrahepatic cholangiocarcinoma vs extrahepatic cholangiocarcinoma vs gallbladder cancer). Patient-reported outcomes were assessed as a secondary outcome in all participants who completed the European Organisation for Research and Treatment of Cancer's 30-item Quality of Life of Cancer Patients questionnaire (QLQ-C30) and the 21-item Cholangiocarcinoma and Gallbladder Cancer Quality of Life Module (QLQ-BIL21). We calculated time to deterioration—ie, time from randomisation to an absolute decrease of at least 10 points in a patient-reported outcome that was confirmed at a subsequent visit or the date of death (by any cause) in the absence of deterioration—and adjusted mean change from baseline in patient-reported outcomes.

Findings

Between April 16, 2019, and Dec 11, 2020, 685 participants were enrolled and randomly assigned, 341 to the durvalumab group and 344 to the placebo group. Overall, 345 (50%) of participants were male and 340 (50%) were female. Data for the QLQ-C30 were available for 318 participants in the durvalumab group and 328 in the placebo group (median follow-up 9·9 months [IQR 6·7 to 14·1]). Data for the QLQ-BIL21 were available for 305 participants in the durvalumab group and 322 in the placebo group (median follow-up 10·2 months [IQR 6·7 to 14·3]). The proportions of participants in both groups who completed questionnaires were high and baseline scores were mostly similar across treatment groups. For global health status or quality of life, functioning, and symptoms, we noted no difference in time to deterioration or adjusted mean changes from baseline were observed between groups. Median time to deterioration of global health status or quality of life was 7·4 months (95% CI 5·6 to 8·9) in the durvalumab group and 6·7 months (5·6 to 7·9) in the placebo group (hazard ratio 0·87 [95% CI 0·69 to 1·12]). The adjusted mean change from baseline was 1·23 (95% CI –0·71 to 3·16) in the durvalumab group and 0·35 (–1·63 to 2·32) in the placebo group.

Interpretation

The addition of durvalumab to gemcitabine and cisplatin did not have a detrimental effect on patient-reported outcomes. These results suggest that durvalumab, gemcitabine, and cisplatin is a tolerable treatment regimen in patients with advanced biliary tract cancer.

Funding

AstraZeneca.

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