Pembrolizumab, radiotherapy, and an immunomodulatory five-drug cocktail in pretreated patients with persistent, recurrent, or metastatic cervical or endometrial carcinoma: Results of the phase II PRIMMO study.

Autor: De Jaeghere EA; Department of Medical Oncology (Route 535), Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent, Belgium.; Laboratory of Experimental Cancer Research, Department of Human Structure and Repair, Ghent University, Ghent, Belgium., Tuyaerts S; Gynaecologic Oncology, Department of Oncology, KU Leuven, Leuven, Belgium.; Leuven Cancer Institute, Leuven, Belgium.; Department of Medical Oncology, University Hospital Brussels, Brussels, Belgium.; Laboratory for Medical and Molecular Oncology (LMMO), VUB, Brussels, Belgium., Van Nuffel AMT; Anticancer Fund (ACF), Strombeek-Bever, Belgium., Belmans A; Biostatistics and Statistical Bioinformatics Centre (L-BioStat), KU Leuven, Leuven, Belgium., Bogaerts K; Biostatistics and Statistical Bioinformatics Centre (L-BioStat), KU Leuven, Leuven, Belgium., Baiden-Amissah R; Gynaecologic Oncology, Department of Oncology, KU Leuven, Leuven, Belgium.; Leuven Cancer Institute, Leuven, Belgium., Lippens L; Cancer Research Institute Ghent (CRIG), Ghent, Belgium.; Laboratory of Experimental Cancer Research, Department of Human Structure and Repair, Ghent University, Ghent, Belgium., Vuylsteke P; Department of Hemato-Oncology, Centre Hospitalier Universitaire Université Catholique de Louvain Namur (Sainte-Elisabeth), Namur, Belgium., Henry S; Department of Hemato-Oncology, Centre Hospitalier Universitaire Université Catholique de Louvain Namur (Sainte-Elisabeth), Namur, Belgium., Trinh XB; Department of Gynecologic Oncology and Senology, University Hospital Antwerp, Edegem, Belgium.; Multidisciplinary Oncologic Centre Antwerp (MOCA), University Hospital Antwerp, Edegem, Belgium.; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), Edegem, Belgium., van Dam PA; Department of Gynecologic Oncology and Senology, University Hospital Antwerp, Edegem, Belgium.; Multidisciplinary Oncologic Centre Antwerp (MOCA), University Hospital Antwerp, Edegem, Belgium.; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), Edegem, Belgium., Aspeslagh S; Department of Medical Oncology, University Hospital Brussels, Brussels, Belgium., De Caluwé A; Department of Radiation Oncology, Jules Bordet Institute, Brussels, Belgium.; Department of Radiation Oncology, General Hospital Sint-Maarten, Mechlin, Belgium., Naert E; Department of Medical Oncology (Route 535), Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent, Belgium., Lambrechts D; VIB-KU Leuven Center for Cancer Biology, Leuven, Belgium., Hendrix A; Cancer Research Institute Ghent (CRIG), Ghent, Belgium.; Laboratory of Experimental Cancer Research, Department of Human Structure and Repair, Ghent University, Ghent, Belgium., De Wever O; Cancer Research Institute Ghent (CRIG), Ghent, Belgium.; Laboratory of Experimental Cancer Research, Department of Human Structure and Repair, Ghent University, Ghent, Belgium., Van de Vijver KK; Cancer Research Institute Ghent (CRIG), Ghent, Belgium.; Department of Pathology, Ghent University Hospital, Ghent, Belgium.; Center for Gynecologic Oncology Amsterdam (CGOA), Netherlands Cancer Institute and Amsterdam Medical Center, Amsterdam, The Netherlands., Amant F; Gynaecologic Oncology, Department of Oncology, KU Leuven, Leuven, Belgium.; Center for Gynecologic Oncology Amsterdam (CGOA), Netherlands Cancer Institute and Amsterdam Medical Center, Amsterdam, The Netherlands.; Department of Gynecology and Obstetrics, University Hospitals Leuven, Leuven, Belgium., Vandecasteele K; Cancer Research Institute Ghent (CRIG), Ghent, Belgium.; Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium., Denys HG; Department of Medical Oncology (Route 535), Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium. hannelore.denys@ugent.be.; Cancer Research Institute Ghent (CRIG), Ghent, Belgium. hannelore.denys@ugent.be.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2023 Feb; Vol. 72 (2), pp. 475-491. Date of Electronic Publication: 2022 Aug 12.
DOI: 10.1007/s00262-022-03253-x
Abstrakt: A phase II study (PRIMMO) of patients with pretreated persistent/recurrent/metastatic cervical or endometrial cancer is presented. Patients received an immunomodulatory five-drug cocktail (IDC) consisting of low-dose cyclophosphamide, aspirin, lansoprazole, vitamin D, and curcumin starting 2 weeks before radioimmunotherapy. Pembrolizumab was administered three-weekly from day 15 onwards; one of the tumor lesions was irradiated (8Gyx3) on days 15, 17, and 19. The primary endpoint was the objective response rate per immune-related response criteria (irORR) at week 26 (a lower bound of the 90% confidence interval [CI] of > 10% was considered efficacious). The prespecified 43 patients (cervical, n = 18; endometrial, n = 25) were enrolled. The irORR was 11.1% (90% CI 2.0-31.0) in cervical cancer and 12.0% (90% CI 3.4-28.2) in endometrial cancer. Median duration of response was not reached in both cohorts. Median interval-censored progression-free survival was 4.1 weeks (95% CI 4.1-25.7) in cervical cancer and 3.6 weeks (95% CI 3.6-15.4) in endometrial cancer; median overall survival was 39.6 weeks (95% CI 15.0-67.0) and 37.4 weeks (95% CI 19.0-50.3), respectively. Grade ≥ 3 treatment-related adverse events were reported in 10 (55.6%) cervical cancer patients and 9 (36.0%) endometrial cancer patients. Health-related quality of life was generally stable over time. Responders had a significantly higher proportion of peripheral T cells when compared to nonresponders (p = 0.013). In conclusion, PRIMMO did not meet its primary objective in both cohorts; pembrolizumab, radiotherapy, and an IDC had modest but durable antitumor activity with acceptable but not negligible toxicity.Trial registration ClinicalTrials.gov (identifier NCT03192059) and EudraCT Registry (number 2016-001569-97).
(© 2022. The Author(s).)
Databáze: MEDLINE
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