A Randomized Phase 2 Study of Pembrolizumab With or Without Radiation in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma

Int J Radiat Oncol Biol Phys. 2021 Jan 1;109(1):134-144. doi: 10.1016/j.ijrobp.2020.08.018. Epub 2020 Aug 8.


Purpose: We evaluated the safety and efficacy of pembrolizumab (pembro) ± radiation therapy (RT) in a phase 2 study among patients with progressive, metastatic adenoid cystic carcinoma (ACC).

Methods and materials: Eligible patients had metastatic ACC with progression within the last year and ≥1 measurable lesion. Patients were randomized to pembro alone or with RT to 30 Gy in 5 fractions (pembroRT). The primary endpoint was objective response rate outside the RT field. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and local RT responses.

Results: We randomized 20 patients (10 per arm) from 2017 to 2018. We did not observe objective response outside of the radiation treatment field; stable disease (SD) was the best response in 12 (60%) patients and was not different per arm (7 pembro, 5 pembroRT, P = .65). A tumor growth rate decrease (TGR) of >25% was noted among 7 of 12 patients and >75% in 4 patients. There were local responses in the irradiated field among all evaluable pembroRT patients. Median PFS and OS were 4.5/not reached for pembroRT and 6.6 / 27.2 months for pembro patients. One patient developed grade 3 liver enzyme elevation after 27 cycles of therapy. Correlative analyses confirm low levels of programmed death-ligand 1 expression (PD-L1), and CD8 infiltrating T-cells. We identified associations between local response and both MYB/NFIB translocation and PD-L1 expression and between changes in systemic immune populations and RT.

Conclusions: Pembrolizumab and pembroRT were well tolerated. We observed no objective responses, but 60% of patients with PD before the study achieved SD, the majority with decreased TGR and half (n = 10) with clinical benefit (SD >6 months). We observed favorable local responses within the RT field. Additional strategies are needed to further delay progression and effect response.

Trial registration: ClinicalTrials.gov NCT03087019.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Carcinoma, Adenoid Cystic / drug therapy*
  • Carcinoma, Adenoid Cystic / pathology
  • Carcinoma, Adenoid Cystic / radiotherapy*
  • Combined Modality Therapy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Recurrence
  • Survival Analysis
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • pembrolizumab

Associated data

  • ClinicalTrials.gov/NCT03087019