Pathological outcomes of neoadjuvant osimertinib-based therapies versus chemotherapy in resectable EGFR-mutant NSCLC: A component network meta-analysis.

Abstract

e20067 Background: Neoadjuvent chemotherapy is the current standard for resectable non–small cell lung cancer (NSCLC) yielding modest pathological outcomes. Emerging data demonstrates better outcomes with neoadjuvant use of osimertinib. We performed a component network meta-analysis (CNMA) comparing neoadjuvant osimertinib-based regimens versus chemotherapy alone using direct and indirect evidence. Methods: Phase II–III trials through January 2026 were included. Two treatment components—osimertinib monotherapy and osimertinib plus chemotherapy—were each evaluated independently relative to chemotherapy alone using a frequentist random-effects CNMA. Odds ratios (ORs) were estimated for pathological complete response (pCR), major pathological response (MPR), Nodal downstaging (DS), R0 resection rate, and grade ≥3 adverse events (AEs). Results: Three studies (n = 481) formed a connected network comparing osimertinib-based strategies with chemotherapy alone. Osimertinib monotherapy significantly improved MPR (OR 22.71, 95% CI 4.99–103.28) and pCR (OR 14.94, 95% CI 1.91–117.05). Osimertinib plus chemotherapy also improved MPR (OR 16.66, 95% CI 3.54–78.52) but did not significantly improve pCR (OR 6.12, 95% CI 0.69–54.27). Nodal DS was improved with both osimertinib monotherapy (OR, 2.51; 95% CI, 1.19–5.30) and the combination regimen (OR, 3.27; 95% CI, 1.53–6.98). R0 resection rates did not differ significantly across groups. Osimertinib was associated with fewer grade ≥3 adverse events (OR, 0.29; 95% CI, 0.15–0.57), whereas combination therapy increased severe toxicity (OR, 4.13; 95% CI, 1.53–11.19). Heterogeneity was low to moderate (I² ≈ 0–60%). Conclusions: Neoadjuvant osimertinib-based therapy improved pathological response and nodal downstaging with a more favorable safety profile observed with monotherapy, while R0 resection rates did not differ significantly. These findings support neoadjuvent osimertinib monotherapy as a promising strategy in resectable EGFR-mutant NSCLC. Pathological outcomes vs chemotherapy alone. Outcome Treatment Odds Ratio (95% CI) P-value MPR OSI 22.71 (4.99-103.28) <0.0001 MPR OSI + CT 16.66 (3.54-78.52) <0.0001 pCR OSI 14.94 (1.91-117.05) 0.01 pCR OSI + CT 6.12 (0.69-54.27) 0.104 Nodal DS OSI 2.51 (1.19-5.3) 0.016 Nodal DS OSI + CT 3.27 (1.53-6.98) 0.002 R0 rate OSI 1.40 (0.50-3.92) 0.518 R0 rate OSI + CT 1.47 (0.45-4.83) 0.527 ≥G3 AEs OSI 0.29 (0.15-0.57) <0.001 ≥G3 AEs OSI + CT 1.10 (0.65-1.88) 0.719 Abbreviations: OSI, osimertinib; CT, chemotherapy; MPR, major pathological response; pCR, pathological complete response; DS, nodal downstaging; R0, microscopically margin-negative resection; AEs, adverse events.