Paper - Review

DOI: 10.1038/s41571-019-0173-9

Abstract

The era of personalized medicine
→ for advanced-stage non-small-cell lung cancer
→ began
← when (biomarker-based evidence) of 1⃣ molecular pathway 2⃣ oncogene addiction ← of the tumor → became mandatory
→ for the allocation of specific targeted therapies

The immunotherapy revolution
← e.g. the development of immune-checkpoint inhibitors (ICIs)
→ has dramatically altered → the NSCLC treatment landscape

Compare & contrast
→ the clinical development of 1⃣ immunotherapy 2⃣ oncogene-directed therapy → for NSCLC
∴ Focusing → on the role of predictive biomarkers

Immunotherapy biomarkers
→ are fundamentally different ← from oncogene biomarkers
← 1⃣ in that (they are continuous) ← rather than categorical
← 2⃣ in that (spatially & temporally variable) & (reliant ← on multiple complex interactions) ← rather than (a single & dominant determinant)

The performance of (predictive biomarkers) → for ICIs
→ might be improved ← by combining different markers
→ to reduce the assumptive risks ← associated with each one

Novel combinations
← with 1⃣ chemotherapy 2⃣ ICIs
→ complicated biomarker discovery
→ do NOT decrease → the value of the markers identified

Perfectly predictive biomarkers of benefit
← from immunotherapy
→ are unlikely to be identified
← 1⃣ exclusionary biomarkers of minimal benefit 2⃣ an unacceptable risk of toxicity
→ might be feasible

The clinical adoption of applicability of (such biomarkers)
→ might vary
← depending on 1⃣ line of treatment 2⃣ the available therapeutic alternatives 3⃣ health economic considerations

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