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 M T;Belmans, Ann;Denys, Hannelore G;et.al.
(2023) Cancer immunology, immunotherapy — Vol. 72, n° 2, p. 475-491 (2023)

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Authors
  • De Jaeghere, Emiel A
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  • Tuyaerts, Sandra
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  • Van Nuffel, An M T
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  • Belmans, Ann
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  • Vuylsteke, PeterUCLouvain
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  • Denys, Hannelore G
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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).
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De Jaeghere, E. A., Tuyaerts, S., Van Nuffel, A. M. T., Belmans, A., Bogaerts, K., Baiden-Amissah, R., Lippens, L., Vuylsteke, P., Henry, S., Trinh, X. B., van Dam, P. A., Aspeslagh, S., De Caluwé, A., Naert, E., Lambrechts, D., Hendrix, A., De Wever, O., Van de Vijver, K. K., Amant, F., et al. (2023). 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. Cancer immunology, immunotherapy, 72(2), 475-491. https://doi.org/10.1007/s00262-022-03253-x (Original work published 2023)