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

De Jaeghere, Emiel A; Tuyaerts, Sandra; Van Nuffel, An MT; Belmans, Ann; Bogaerts, Kris; Baiden-Amissah, Regina; Lippens, Lien; Vuylsteke, Peter; Henry, Stephanie; Trinh, Xuan Bich; van Dam, Peter A; Aspeslagh, Sandrine; De Caluwe, Alex; Naert, Eline; Lambrechts, Diether; Hendrix, An; De Wever, Olivier; Van de Vijver, Koen K; Amant, Frederic; Vandecasteele, Katrien; Denys, Hannelore G

doi:10.1007/s00262-022-03253-x

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

Author:

De Jaeghere, Emiel A

Tuyaerts, Sandra ; Van Nuffel, An MT ; Belmans, Ann ; Bogaerts, Kris ; Baiden-Amissah, Regina ; Lippens, Lien ; Vuylsteke, Peter ; Henry, Stephanie ; Trinh, Xuan Bich ; van Dam, Peter A ; Aspeslagh, Sandrine ; De Caluwe, Alex ; Naert, Eline ; Lambrechts, Diether ; Hendrix, An ; De Wever, Olivier ; Van de Vijver, Koen K ; Amant, Frederic ; Vandecasteele, Katrien ; Denys, Hannelore G

Keywords:

Science & Technology, Life Sciences & Biomedicine, Oncology, Immunology, Radioimmunotherapy, Drug therapy, combination, Gynecologic neoplasms, Immunomodulation, Tumor microenvironment, SOLID TUMORS, RADIATION-THERAPY, CANCER-PATIENTS, CYCLOPHOSPHAMIDE, CEMIPLIMAB, EFFICACY, SAFETY, CHEMOTHERAPY, COMBINATION, GUIDELINES, Drug therapy, combination, Female, Humans, Uterine Cervical Neoplasms, Quality of Life, Antibodies, Monoclonal, Humanized, Endometrial Neoplasms, CELL CARCINOMA, 1107 Immunology, 3204 Immunology, 3211 Oncology and carcinogenesis

Abstract:

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).