The trial's 57.1% pathologic complete response (pCR) rate is deceptively conservative. It categorized patients who responded well but declined surgery as non-responders, suggesting the treatment's true biological efficacy is even higher than the already impressive reported figure.

Developers often test novel agents in late-line settings because the control arm is weaker, increasing the statistical chance of success. However, this strategy may doom effective immunotherapies by testing them in biologically hostile, resistant tumors, masking their true potential.

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.

An overall survival (OS) benefit in an adjuvant trial may not be meaningful for patients in systems (e.g., the U.S.) with guaranteed access to the same effective immunotherapy upon recurrence. The crucial, unanswered question is whether treating micrometastatic disease is inherently superior to treating macroscopic disease later, a distinction current trial data doesn't clarify.

The success of perioperative osimertinib means oncologists cannot choose the optimal strategy (targeted therapy vs. chemoimmunotherapy) for resectable lung cancer without first knowing the patient's EGFR, ALK, and PD-L1 status. This elevates biomarker profiling from a metastatic-setting tool to a critical first step in early-stage disease.

Experts believe the stark difference in complete response rates (5% vs 30%) between two major ADC trials is likely due to "noise"—variations in patient populations (e.g., more upper tract disease) and stricter central review criteria, rather than a fundamental difference in the therapies' effectiveness.

Immunotherapies can be effective even without causing significant tumor shrinkage. Immunocore's drug KimTrack had a low 5-7% objective response rate (ORR) but demonstrated a massive overall survival (OS) benefit, challenging the reliance on traditional chemotherapy metrics for evaluating modern cancer treatments.

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.