91P - The impact of the immunological context on outcomes of solid cancer patients treated with genotype-matched targeted therapies: A systematic review

Background

The integration of targeted therapy regimens in oncological care has shifted the paradigm of cancer treatment. However, up to 30% of patients with actionable mutations exhibit no initial response to treatment. There is a critical need for the development of stratification approaches to distinguish the characteristics of treatment non-responders and responders so that appropriate treatment is provided, and patient expectations can be adjusted accordingly. We conducted a systematic review to assess whether the immune composition at baseline has a role in determining outcome of targeted therapies in patients with genetic aberrations.

Methods

A systematic literature search of Web of Science, Embase and Medline was conducted up to the 15^th of July to identify relevant studies. A meta-analysis was performed on RevMan 5.4 when 3 or more studies reported the same biomarker and provided outcome data of overall survival (OS) or progression-free survival (PFS). Other studies were analysed qualitatively.

Results

55 studies were eligible for quantitative analysis focused on EGFR, BRAF, ALK and HER2 mutant patients. A high neutrophil-to-lymphocyte ratio was a poor prognostic marker across all mutations for PFS and OS. PD-L1 high expression was predictive of outcome levels in EGFR (PFS, HR 1.77, 95% CI 1.32–2.37; OS, HR 1.17, 95% CI 0.99–1.38) and ALK-rearranged lung cancer (PFS, HR 1.87, 95% CI 1.21–2.88; OS, HR 2.04, 95% CI 1.13–3.69) but not in BRAF-mutant melanoma. 12 studies reported a significant role for tumour-infiltrating lymphocytes (TILs) as a predictive/prognostic marker, with particularly promising results following stratification of patients based on CD8+ TIL levels in combination with PD-L1 expression or B-cell levels. Other studies implicated macrophages and inflammatory cytokines, such as IL-6 and IFNγ, to be of value.

Conclusions

The results of this review highlight the need to move beyond the simple assessing of presence or absence of targeted genomic aberrations to a more contextualised precision medicine that specifically acknowledges the role of the immunological context that a mutation is inscribed upon in determining outcome of targeted therapy treatment.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

G. Middleton.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.