Unlike rare biomarkers that necessitate a 'test-and-wait' approach, IB6 is expressed in over 80-90% of NSCLC tumors. This ubiquity could make pre-screening unnecessary for drugs like Sigvotatug Vedotin, allowing clinicians to initiate targeted therapy much faster and for a broader patient population.

The future of medicine isn't about finding a single 'best' modality like CAR-T or gene therapy. Instead, it's about strategic convergence, choosing the right tool—be it a bispecific, ADC, or another biologic—based on the patient's specific disease stage and urgency of treatment.

Experts believe molecular tests like Decipher and PTEN status are superior to simply counting bone lesions for guiding treatment. While not yet standard practice for all decisions, this represents a significant shift towards using underlying tumor biology to determine therapy, like adding docetaxel.

The InVigor11 study was the first to show that detecting recurrence via a ctDNA test before it's visible on scans is not just a prognostic sign, but an actionable clinical state. Intervening with therapy at this early stage was proven to improve patient outcomes, establishing a new paradigm for cancer surveillance.

Before the LAURA trial, oncologists had strong data for using EGFR TKIs in metastatic and resectable settings but lacked evidence for the unresectable Stage 3 population receiving chemoradiation. LAURA filled this "awkward gap," confirming a long-held suspicion and harmonizing treatment strategy across disease stages.

Unlike immunotherapy, neoadjuvant osimertinib yields poor pathologic complete response (pCR) rates. However, it significantly improves major pathologic response (MPR) and survival, suggesting pCR may be the wrong efficacy endpoint for cytostatic EGFR TKIs, which have a different mechanism of action than immunotherapy.

The ongoing Phase III trial for Sigvotatug Vedotin compares it against docetaxel, the current standard for second-line NSCLC. Docetaxel is known for modest efficacy and significant side effects, creating a major opportunity for the new drug to demonstrate superiority and rapidly become the new clinical standard.

A sobering finding from the LAURA trial was its control arm. EGFR-mutant patients receiving standard "curative-intent" chemoradiation alone had extremely high and rapid relapse rates (PFS ~6 months), highlighting the inadequacy of this standard and underscoring the necessity of adding consolidation osimertinib.

For N2+ EGFR-mutant NSCLC, clinicians now face a choice. Combining neoadjuvant osimertinib with chemotherapy is potent and gets treatment done upfront, but osimertinib monotherapy is better tolerated, reducing the risk of toxicity that could prevent a patient from reaching their planned surgery.