Estimated clinical efficacy and radiographic response characteristics of PD1 inhibition in newly diagnosed and recurrent glioblastoma in clinical practice: A report from the iRANO Working Group

Autor: Elizabeth George, Javier Villanueva-Meyer, Raymond Y. Huang, Geoffrey S. Young, Jacob Schlossman, Susan M. Chang, Talia Oughourlian, Mary Jane Lim-Fat, Benjamin M. Ellingson, Michael Weller, Catalina Raymond, Patrick Y. Wen, Bryan Iorgulescu, David A. Reardon, Tyler Gleason, Nancy Ann Oberheim Bush, Timothy F. Cloughesy, Hideho Okada
Rok vydání: 2020
Předmět:
Zdroj: Journal of Clinical Oncology. 38:2521-2521
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2020.38.15_suppl.2521
Popis: 2521 Background: Despite concerns of immunotherapy-induced inflammatory response during PD1 inhibition, questions remain as to the true incidence of inflammatory response and potential clinical implications. The goals of the project were to use GBM patients pooled from academic centers to estimate radiographic PFS and OS, as well as determine the incidence of immunotherapy-induced inflammatory response. Methods: 152 patients with newly diagnosed (N = 57) or recurrent (N = 95) GBM treated with either nivolumab or pembrolizumab from Dana-Farber (N = 88), UCLA (N = 35) or UCSF (N = 29) were included in this study. Radiographic progression was defined by a 25% increase in bidirectional measurements according to RANO. Results: Median PFS and OS for newly diagnosed patients was 162 and 520 days, respectively, while median PFS and OS for recurrent patients was 72 and 225 days, respectively. No difference in OS was observed in recurrent patients treated with nivolumab vs. pembrolizumab (P = 0.58), but recurrent patients treated with nivolumab trended toward a longer PFS (P = 0.097). Of the recurrent patients with OS and PFS data available and radiographic progression, 95% of them progressed within 6 mos of starting treatment. Median post-progression survival (PPS) in recurrent patients with PFS < 6 mos was 151 days, while PPS for patients with PFS > 6 mos was 178 days (P = 0.51). In the 77 recurrent patients who progressed within 6 mos, 36.4% had an OS that was > 9 mos, while 63.6% had an OS < 9 mos, suggesting the majority of patients with “early progression” also died early and a minority of patients had what could be considered “immune-related inflammation”. Of the 81 recurrent patients with documented progression, only 2.5% showed stabilization within 3 mos of first progression, 30.9% died before the 3-month confirmation scan could be obtained, 24.7% showed continued tumor growth by 3 months, and 48.1% had no follow-up confirmatory imaging exams. Of the 70 patients who progressed within 6 mos and had documented death, 2.9% had disease stabilization, 31.4% died before the 3-month confirmation, and 75.7% had either documented tumor growth or had no follow-up confirmatory imaging exams. Conclusions: This study suggests immunotherapy-induced inflammation followed by a favorable PPS is uncommon in GBM. While patients treated with other types of immunotherapy may exhibit different imaging characteristics, these data provide an important basis to refine the iRANO criteria.
Databáze: OpenAIRE