Data from ERK1/2 Phosphorylation Predicts Survival in Recurrent Glioblastoma Following Intracerebral and Adjuvant PD-1/CTLA-4 Immunotherapy: A REMARK-guided Analysis

• DOI: 10.1158/1078-0432.c.7029263
• Publication Date: 2024-01-17T08:20:17Z
• Authors: Víctor A. Arrieta; Johnny Duerinck; Kirsten B. Burdett; Karl J. Habashy; Wietse Geens; Andrew Gould; Julia K. Schwarze; Crismita Dmello; Kwang-Soo Kim; Ruth Saganty; Li Chen; Alberto Moscona; Matthew McCord; Catalina Lee-Chang; Craig M. Horbinski; Hui Zhang; Roger Stupp; Bart Neyns; Adam M. Sonabend
• Keywords: Adjuvant Therapy

<div>AbstractPurpose:<p>Evidence suggests that MAPK pathway activation, as measured by ERK1/2 phosphorylation (p-ERK), predicts overall survival (OS) in patients with recurrent glioblastoma receiving anti-PD-1 therapy. We aimed to validate these findings independent cohorts.</p>Experimental Design:<p>In a 24-patient clinical trial on and high-grade gliomas, we examined the link between p-ERK levels OS. Patients received intravenous nivolumab, followed maximal safe resection an intracerebral injection of either ipilimumab alone or combined nivolumab. Biweekly adjuvant nivolumab was then administered up five times (NCT03233152). Using REporting recommendations for tumor MARKER prognostic studies (REMARK) criteria, conducted analyses quantification statistical evaluations. Additional comparative analysis included prior cohorts, totaling 65 patients. Cox proportional hazards models meta-analysis were employed assess predictive biomarker after immunotherapy.</p>Results:<p>Lower median p-ERK+ cell density observed compared studies, likely due variable tissue processing across cohorts. Nonetheless, high associated prolonged OS, particularly isocitrate dehydrogenase wild-type glioblastomas (<i>P</i> = 0.036). Median OS low 55.6 30 weeks, respectively. Multivariable reinforced p-ERK's significance prediction 0.011). Upon normalization cohorts (<i>n</i> 65), supported benefit elevated 0.0424).</p>Conclusions:<p>This study strengthens role immune checkpoint blockade. Future research should focus further validation prospective trials standardization preanalytical variables influencing quantification.</p></div>