471P - PTEN alteration as a predictor of second-line efficacy in patients with recurrent IDHwt-glioblastoma

Background

Nitrosoureas (lomustine or fotemustine) and antiangiogenic (bevacizumab or regorafenib) are second-line treatment options for patients with rGBM, but to date predictors or efficacy are lacking. PTEN mutations are common in GBM, but their potential predictive role has been understudied. We aim to investigate the impact of PTEN alterations on the efficacy of second-line therapy in rGBM.

Methods

We conducted a retrospective single-institution study to assess the combination of pathogenic PTEN alterations (FoundationOne®CDx on tissue), and clinical data (molecular and histological characteristics, treatment details and outcomes) in a cohort of consecutive patients with first rGBM treated with Reg, NS or Bev alone at Veneto Institute of Oncology (Padua, Italy) from Oct 2019 to Jan 2023. WHO2021 classification was used for pathological diagnosis, and RANO criteria for neuroradiologic response evaluation.

Results

153 patients were enrolled, treated with Reg (n=95), Bev (n=19), NS (n=39). The mOS from the start of treatment was, respectively: 12m (95% CI 9.1-14), 7.0m (95% CI 6.0-11) and 8.0 months (95% CI 5.0-13) PTEN was altered respectively in: 58 pts (61%), 8 pts (57%) and in 23 pts (58%). In univariate analysis PTEN alteration was associated with short survival in Reg cohort (mOS of 10.4 m VS 16.8 m alterated versus wt PTEN, respectively; HR 1.68, p=0.043) and Lomustine cohort (mOS of 6.0m VS 16m in alterated versus wild-type PTEN, respectively; HR 1.27, p=0.01). In contrast, in Bev cohort PTEN alteration did not reach a statistical significance in univariate analysis. Of note, in multivariate analysis adjusted for categorical age (threshold,65 yrs), second surgery, ECOG score (0-1 vs. 2) and steroid use. PTEN alteration maintained a significant impact as predictor of short survival after treatment for both regorafenib and lomustine cohort (HR 1.67, p=0.043 and HR=3.17, p=0.003, respectively) together with MGMT methylation status (HR 0.44, p=0.002 and HR=0.33, p=0.006, respectively).

Conclusions

We concluded that pathogenic PTEN alteration may be a predictor of poor efficacy of regorafenib and lomustine in rGBM patients. However, a prospective study with a larger population is needed to better define the role of PTEN.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

G. Lombardi: Financial Interests, Personal and Institutional, Advisory Board: AbbVie, Bayer, Novartis, Orbus Therapeutics, BrainFarm, Celgene, Cureteq, Health4U, Braun, Janssen, BioRegio, STERN, Servier, Novocure, Roche. All other authors have declared no conflicts of interest.