Long-term, longitudinal safety of first-line osimertinib plus platinum–pemetrexed (induction × 4 cycles, then osimertinib + pemetrexed maintenance, then osimertinib alone) versus osimertinib monotherapy in patients with EGFR-mutated advanced NSCLC, analyzed across three distinct treatment periods in the combination arm (n = 276).
Grade ≥ 3 treatment-related AE onset frequency declined progressively from 43% (induction) → 25% (pemetrexed maintenance) → 14% (osimertinib-only period); rates of AEs leading to osimertinib discontinuation were ≤8% across all periods. Median durations were 2.8, 12.4, and 17.8 months for each respective period.
Post-hoc, single-arm analysis of the combination group only — no direct safety comparison to the monotherapy arm is presented. Patient numbers decline across periods (n = 276 → 201 → 206), reflecting attrition. Renal toxicity signal during pemetrexed maintenance (19%) warrants prospective monitoring but was entirely grade 1/2 in this dataset.
Clinicians can reassure patients that the most intense toxicity burden (hematologic, GI, skin/nail) is concentrated in the 4-cycle induction phase and diminishes significantly over time. Renal toxicity, however, peaks during pemetrexed maintenance and should be monitored proactively throughout that period.
