Re-irradiation plus pembrolizumab: Phase II study for recurrent glioblastoma patients.

Autor:	Iwamoto FM; Columbia University, New York, NY, United States., Tanguturi SK; Brigham and Women's Hospital, Boston, Massachusetts, United States., Nayak L; Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts, United States., Wang TJ; Columbia University Medical Center, New York, New York, United States., Desai A; University of Pennsylvania, Philadelphia, PA, United States., Lustig RA; University of Pennsylvania, Philadelphia, PA, United States., Bagley S; University of Pennsylvania, Philadelphia, Pa, United States., Wong ET; Beth Israel Deaconess Med Ctr, Boston, MA, United States., Hertan LM; Beth Israel Deaconess Medical Center, Boston, MA, United States., McCluskey C; Dana-Farber Cancer Institute, Boston, MA, United States., Hayden J; Massachusetts General Hospital, Boston, MA, United States., Muzikansky A; Massachusetts General Hospital, Boston, MA, United States., Nakhawa S; Dana-Farber Cancer Institute, Boston, MA, United States., Japo J; Dana-Farber Cancer Institute, United States., Bossi CC; Dana-Farber Cancer Institute., Meylan M; Centre de Recherche des Cordeliers, Inserm UMRS 1138, Paris, France., Tian Y; Dana-Farber Cancer Institute, United States., Barlow GL; Dana-Farber Cancer Institute, United States., Speliakos P; Dana-Farber Cancer Institute, United States., Ayoub G; Dana-Farber Cancer Institute, Boston, United States., Meredith DM; Dana-Farber Cancer Institute, United States., Ligon KL; Dana-Farber Cancer Institute, Boston, MA, United States., Haas-Kogan D; Dana-Farber Cancer Institute, Boston, MA, United States., Huang K; Dana-Farber/Brigham and Women's Cancer Center, United States., Wucherpfennig KW; Dana-Farber Cancer Institute, Boston, MA, United States., Wen PY; Dana-Farber Cancer Institute, Boston, MA, United States., Reardon DA; Dana-Farber Cancer Institute, Boston, MA, United States.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Nov 08. Date of Electronic Publication: 2024 Nov 08.
DOI:	10.1158/1078-0432.CCR-24-1629
Abstrakt:	Purpose: Radiation therapy may enhance anti-tumor immune responses by several mechanisms including induction of immunogenic cell death. We performed a phase 2 study of pembrolizumab with re-irradiation in patients with recurrent glioblastoma. Methods: Sixty recurrent glioblastoma patients received pembrolizumab with re-irradiation alone (cohort A, bevacizumab-naïve; n=30) or with bevacizumab continuation (cohort B, n=30). Dual primary endpoints including overall response rate (ORR) and overall survival at either 12 (OS-12; cohort A) or six months (OS-6; cohort B) were assessed per cohort relative to historical benchmarks. Paired paraffin-embedded formalin-fixed tumor samples were assessed for immunologic biomarkers by immunohistochemistry using digital quantification and Co-Detection-by-InDEXing (CODEX). Results: Study therapy was well tolerated with most toxicities being grade ≤ 3. For cohort B, the primary endpoint of OS-6 was achieved (57%), however survival was not improved for cohort A patients. The ORR was 3.3% and 6.7% for cohorts A and B, respectively. CODEX analysis of paired tumor samples from 5 patients revealed an increase of activated T cells in the tumor microenvironment after study therapy. Conclusions: Compared to historical controls, re-irradiation plus pembrolizumab appeared to improve survival among bevacizumab-refractory patients but not among bevacizumab-naïve patients. CODEX revealed evidence of intratumoral infiltration of activated immune effector cells. A randomized, properly controlled trial of PD-1 blockade plus re-irradiation is warranted to further evaluate this regimen for bevacizumab refractory patients, but alternative approaches are needed for bevacizumab-naïve patients.
Databáze:	MEDLINE
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