Cancer Immunology, Immunotherapy (Aug 2022)

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

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

DOI
https://doi.org/10.1007/s00262-022-03253-x
Journal volume & issue
Vol. 72, no. 2
pp. 475 – 491

Abstract

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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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