84P - Advancing precision oncology: Integrating immune landscape and genomics for tailored therapy in metastatic cancer patients

Background

Molecular-targeted therapies have revolutionized the treatment landscape for metastatic cancer patients. Understanding the tumor immune microenvironment, particularly the presence of mature tertiary lymphoid structures (mTLS), is emerging as a critical determinant of response to immune checkpoint inhibitors (ICIs). Integrating immune and molecular profiles is pivotal for personalized medicine.

Methods

The ongoing precision medicine study BIP (Institut Bergonié, Bordeaux, France, NCT02534649) was amended to integrate immune profiling besides next-generation sequencing for patients with available tumor material. ctDNA and tissue NGS was performed using FoundationOne®CDx panel. mTLS status, was evaluated centrally using immunohistochemistry with CD3/CD20/CD23 markers. Primary objective: Evaluate therapeutic orientation post immuno-molecular characterization. Secondary endpoints: i) Descriptive analysis of oriented-treated population, ii) Outcome analysis, iii) Correlation between MP and mTLS status (χ² test).

Results

Between July 2021 and July 2023, 2870 pts underwent molecular screening, with 300 completing both tumoral tissue molecular and immune profiling. Common tumor types included breast, prostate, and ovarian cancers (25.3%, 15.7%, and 8.3% respectively). Median previous lines were 2 (IQR 1-3). mTLS was observed in 122 patients (40.6%). We found KRAS (N=54; 66.6%) and APC (N=33; 71.7%) as strongly correlated with mTLS status (p < 0.05 χ² test). We found no correlation between tumor mutational burden (TMB) and mTLS status (p=0.8 χ² test). Based on molecular alterations, 29% of pts were oriented to targeted therapies, while 35.6% were directed to immunotherapy based on positive mTLS. 11% were oriented based on both. Overall, 5 pts (1.6%) received molecular targeted therapy and 6 pts (2%) received mTLS-oriented immunotherapy. Among 11 pts treated, we identified 3 partial response and 2 stable disease.

Conclusions

Integration of immune and molecular profiling enhances therapeutic options for cancer patients within a personalized medicine framework. We identified KRAS and APC as strongly correlated with mTLS, emphasizing the potential for tailored immunotherapy.

Clinical trial identification

NCT02534649.

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.