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Verfasst von:Haag, Georg Martin [VerfasserIn]   i
 Springfeld, Christoph [VerfasserIn]   i
 Grün, Barbara [VerfasserIn]   i
 Apostolidis, Leonidas [VerfasserIn]   i
 Zschäbitz, Stefanie [VerfasserIn]   i
 Dietrich, Mareike [VerfasserIn]   i
 Berger, Anne Katrin [VerfasserIn]   i
 Weber, Tim [VerfasserIn]   i
 Zörnig, Inka [VerfasserIn]   i
 Schaaf, Marina [VerfasserIn]   i
 Waberer, Lisa [VerfasserIn]   i
 Müller, Daniel Wilhelm [VerfasserIn]   i
 Al-Batran, Salah-Eddin [VerfasserIn]   i
 Halama, Niels [VerfasserIn]   i
 Jäger, Dirk [VerfasserIn]   i
Titel:Pembrolizumab and maraviroc in refractory mismatch repair proficient/microsatellite-stable metastatic colorectal cancer
Titelzusatz:the PICCASSO phase I trial
Verf.angabe:Georg Martin Haag, Christoph Springfeld, Barbara Grün, Leonidas Apostolidis, Stefanie Zschäbitz, Mareike Dietrich, Anne-Katrin Berger, Tim Frederik Weber, Inka Zoernig, Marina Schaaf, Lisa Waberer, Daniel Wilhelm Müller, Salah-Eddin Al-Batran, Niels Halama, Dirk Jaeger
E-Jahr:2022
Jahr:12 April 2022
Umfang:11 S.
Fussnoten:Gesehen am 20.06.2022
Titel Quelle:Enthalten in: European journal of cancer
Ort Quelle:Amsterdam [u.a.] : Elsevier, 1992
Jahr Quelle:2022
Band/Heft Quelle:167(2022), Seite 112-122
ISSN Quelle:1879-0852
Abstract:Background - PD-1/PD-L1 inhibitors do not show activity in mismatch repair proficient (MMRp) colorectal cancer. Inhibition of C-C motif chemokine receptor 5 (CCR5) leads to an antitumoral activation of macrophages, affecting immune cell infiltrates. PICCASSO is a phase I trial exploring safety and efficacy of pembrolizumab and maraviroc in refractory MMRp CRC. - Methods - Twenty patients received pembrolizumab and maraviroc (core period, eight cycles), followed by pembrolizumab monotherapy. Primary endpoint was the feasibility rate (patients without treatment-related grade ≥3 immune-related adverse events, treatment-related grade ≥4 adverse events, or any toxicity-related premature withdrawal of treatment). Secondary endpoints included safety/toxicity, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Optional biopsies of liver metastases were performed for analyses of the micromilieu. - Results - The feasibility rate was 94.7% [90% CI 77.4-99.7%], with one grade 4 hyperglycemia and no additional ≥ grade 3 treatment-related toxicities. ORR according to RECIST was 5.3%. Median PFS according to RECIST was 2.10 months [95%CI 1.68-2.30], median OS 9.83 months [95% CI, 5.59-20.02]. Disease control rate of poststudy salvage treatment was >70%. Translational analyses showed an increase of antitumoral chemokines during treatment; eotaxin, a chemokine involved in chemotaxis, was identified as a biomarker linked to OS. - Conclusions - Therapy with pembrolizumab and maraviroc was feasible and showed a beneficial toxicity pattern. Clinical activity in MMRp CRC patients was limited with prolonged disease stabilizations observed in single patients. Efficacy of poststudy salvage treatment and OS was higher than expected in this heavily pretreated population. - This trial is registered at clinicaltrials.gov - NCT03274804.
DOI:doi:10.1016/j.ejca.2022.03.017
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1016/j.ejca.2022.03.017
 Volltext: https://www.sciencedirect.com/science/article/pii/S0959804922001617
 DOI: https://doi.org/10.1016/j.ejca.2022.03.017
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Chemokine
 Colorectal cancer
 Micromilieu
 Mismatch repair proficient
 PD-1 blockade
K10plus-PPN:1807273687
Verknüpfungen:→ Zeitschrift

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