Real-world data demonstrates that a subset of node-negative (N0) breast cancer patients with high-risk features has a recurrence and mortality rate nearly identical to that of node-positive (N1) patients. This finding justifies intensifying adjuvant therapy with agents like CDK4/6 inhibitors for this seemingly lower-risk group, as was done in the NATALEE trial.

The North Star study shows local therapy like radiation or surgery improves survival in stage IV patients on osimertinib, but only if every site of residual disease is treated. Treating some but not all spots provides no additional benefit over standard TKI therapy.

The NeoADURA trial demonstrates that adding osimertinib in the neoadjuvant setting for EGFR-mutated NSCLC results in a 'humongous benefit' in major pathological response and nodal downstaging compared to chemotherapy alone, significantly improving surgical outcomes.

The FLORA two study's overall survival benefit was so compelling that clinicians should now default to osimertinib plus chemotherapy for most first-line EGFR-mutant NSCLC patients, only opting out for specific reasons like comorbidities or patient preference.

For premenopausal patients with extensive nodal disease (e.g., N2), the clinical indication for chemotherapy is so strong that even a low-risk genomic score would not be enough to withhold treatment. This highlights the primacy of clinical staging over genomic data in certain high-risk scenarios.

When EGFR+ NSCLC transforms to small cell, clinicians often continue the TKI osimertinib alongside chemotherapy. This practice is largely based on expert consensus and the rationale of suppressing any remaining EGFR-driven clones, rather than on definitive clinical trial data showing a clear benefit.

Data from the ADAURA trial suggests that EGFR-mutated lung cancer patients with detectable ctDNA before starting adjuvant osimertinib are at very high risk of recurrence. This finding supports considering indefinite, lifelong osimertinib for this subgroup, deviating from the standard three-year duration.

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.

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.