Heinz-Josef Lenz

The first credible response signal in microsatellite stable colorectal cancer, and the reason the field's attention has moved to Fc engineering and to excluding patients with active liver metastases, in whom responses are rare.

Combination checkpoint blockade became a first-line standard for mismatch repair-deficient metastatic colorectal cancer in 2025; the later all-lines comparison against nivolumab alone showed the CTLA-4 antibody adds to the PD-1 antibody, the first phase 3 to prove that in this disease.

It is the strongest evidence that the consensus subtypes could choose between the two first-line biologicals, and the clearest statement of why they have not: it is a retrospective analysis of a subset of one trial, on an assay nobody has validated for clinical use.

The negative counterweight to FIRE-3. The two trials are reconciled only by primary tumour side, which is why the sidedness analysis rather than either trial is what guidelines now cite.

It showed the sidedness effect is not an artefact of pooling and survives adjustment for BRAF, which is what made guideline committees act on it.

The analysis that put 'left-sided, RAS and BRAF wild-type' into every guideline as the anti-EGFR population, and made an anatomical fact into a treatment-selection biomarker.

Trifluridine-tipiracil became the other refractory-line standard alongside regorafenib, and the backbone that SUNLIGHT later improved on by adding bevacizumab.

The start of the refractory-line era in colorectal cancer: a survival benefit measured in weeks, with real toxicity, which is why dose-escalation strategies and patient selection have occupied the field since.