457P - Progression-free survival 2 (PFS2) as a surrogate for overall survival in a multicentric real-world data cohort of glioblastoma (GBM)

Background

GBM is the most common and aggressive primary brain tumor (pBT) with almost unavoidable recurrence. Unfortunately, many late-stage clinical trials fail to replicate preliminary results from early-stage trials, especially important in first-line due to pseudoprogression. Our aim is to compare the association between OS, PFS and PFS2 calculated from the start of initial treatment to the time of disease progression on subsequent therapy, which appears to have a stronger correlation with OS. We also analyze the impact of different treatments after disease progression and the presence of actionable mutations in PFS2.

Methods

GBM patients (pts) included in an observational cohort from 7 Spanish institutions with next-generation sequencing performed between 2018 and 2022 were analyzed. Correlations between OS and both PFS2 and PFS1 were calculated using the iterative multiple imputation approach for estimating the rank correlation under a normal copula, with a complementary analysis based on the proposed ESCAT classification for pBT presented by Mirallas O, et al [ESMO 2023].

Results

We included 405 pts with GBM. Most pts were treated with conventional scheme of TMZ and radiation. A second-line chemotherapeutic agent was administered to 378 pts. Median OS (mOS) and PFS (mPFS) were 25 and 12 months (mo) respectively. High mOS probably related to the temporal selection bias due to NGS. Median PFS2 (mPFS2) was 16 mo. The correlation coefficient between OS and PFS was 0.8 (95% CI, 0.75-0-84), while for PFS2, it was 0.85 (95% CI, 0.81-0,88). A significant difference was found between Tier I-II and III-IV in terms of mPFS2 (25 vs 16 mo respectively, HR 2.06, p 0.025). mOS was not reached in tier I-II patients and resulted 25 mo in tier III-IV. Between second-line options, mPFS2 was 13 mo for bevacizumab, 9.7 mo for lomustine, 12 mo for the combination irinotecan plus bevacizumab, 18 mo for temozolomide.

Conclusions

PFS2 has a stronger correlation with OS than PFS and may be influenced by the chosen second-line therapy, especially when patients with ESCAT I-II molecular alteration only have access to targeted treatment at relapse, thus PFS2 could potentially be used when the choice of first-line therapy may bias the assessment of PFS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.