Buchumschlag

Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial

Cancer of unknown primary has a dismal prognosis, especially following failure of platinum-based chemotherapy. 10-20% of patients have a high tumor mutational burden (TMB), which predicts response to immunotherapy in many cancer types. In this prospective, non-randomized, open-label, multicenter Pha...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Pouyiourou, Maria (VerfasserIn) , Kraft, Bianca (VerfasserIn) , Wohlfromm, Timothy (VerfasserIn) , Stahl, Michael (VerfasserIn) , Kubuschok, Boris (VerfasserIn) , Löffler, Harald (VerfasserIn) , Hacker, Ulrich T. (VerfasserIn) , Hübner, Gerdt (VerfasserIn) , Weiss, Lena (VerfasserIn) , Bitzer, Michael (VerfasserIn) , Ernst, Thomas (VerfasserIn) , Schütt, Philipp (VerfasserIn) , Hielscher, Thomas (VerfasserIn) , Delorme, Stefan (VerfasserIn) , Kirchner, Martina (VerfasserIn) , Kazdal, Daniel (VerfasserIn) , Ball, Markus (VerfasserIn) , Kluck, Klaus (VerfasserIn) , Stenzinger, Albrecht (VerfasserIn) , Bochtler, Tilmann (VerfasserIn) , Krämer, Alwin (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 24 October 2023
In: Nature Communications
Year: 2023, Jahrgang: 14, Pages: 1-21
ISSN:2041-1723
DOI:10.1038/s41467-023-42400-5
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-023-42400-5
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41467-023-42400-5
Volltext
Verfasserangaben:Maria Pouyiourou, Bianca N. Kraft, Timothy Wohlfromm, Michael Stahl, Boris Kubuschok, Harald Löffler, Ulrich T. Hacker, Gerdt Hübner, Lena Weiss, Michael Bitzer, Thomas Ernst, Philipp Schütt, Thomas Hielscher, Stefan Delorme, Martina Kirchner, Daniel Kazdal, Markus Ball, Klaus Kluck, Albrecht Stenzinger, Tilmann Bochtler & Alwin Krämer
Beschreibung
Zusammenfassung:Cancer of unknown primary has a dismal prognosis, especially following failure of platinum-based chemotherapy. 10-20% of patients have a high tumor mutational burden (TMB), which predicts response to immunotherapy in many cancer types. In this prospective, non-randomized, open-label, multicenter Phase II trial (EudraCT 2018-004562-33; NCT04131621), patients relapsed or refractory after platinum-based chemotherapy received nivolumab and ipilimumab following TMBhigh vs. TMBlow stratification. Progression-free survival (PFS) represented the primary endpoint; overall survival (OS), response rates, duration of clinical benefit and safety were the secondary endpoints. The trial was prematurely terminated in March 2021 before reaching the preplanned sample size (n = 194). Among 31 evaluable patients, 16% had a high TMB ( > 12 mutations/Mb). Overall response rate was 16% (95% CI 6-34%), with 7.7% (95% CI 1-25%) vs. 60% (95% CI 15-95%) in TMBlow and TMBhigh, respectively. Although the primary endpoint was not met, high TMB was associated with better median PFS (18.3 vs. 2.4 months) and OS (18.3 vs. 3.6 months). Severe immune-related adverse events were reported in 29% of cases. Assessing on-treatment dynamics of circulating tumor DNA using combined targeted hotspot mutation and shallow whole genome sequencing as part of a predefined exploratory analysis identified patients benefiting from immunotherapy irrespective of initial radiologic response.
Beschreibung:Gesehen am 17.05.2024
Beschreibung:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-023-42400-5

Ähnliche Einträge