Background
Phase II RCT (WJOG9717L); N=122; treatment-naive EGFR-mutant advanced NSCLC; randomized to osimertinib +/- ramucirumab.
Interventions and follow up
Arm A: Osimertinib 80 mg PO daily + ramucirumab 10 mg/kg IV q2wk
Arm B: Osimertinib 80 mg PO daily
Primary endpoint: PFS
mFollow up: 19.8 mo
Arm B: Osimertinib 80 mg PO daily
Primary endpoint: PFS
mFollow up: 19.8 mo
Results
mPFS: 22.1 mo vs 20.2 mo; HR 0.862 (95%CI 0.531–1.397); P=.213
mOS: not mature
mOS: not mature
Adverse events
Grade ≥3 overall: 56% vs 48%
Cardiovascular: hypertension 34% vs 8%
Renal: proteinuria 54% vs 7%
Skin/nail: paronychia 66% vs 45%; acneiform rash 41% vs 20%
Bleeding: epistaxis 36% vs 8%
GI: nausea 25% vs 8%
Ocular: conjunctivitis 12% vs 2%
Pulmonary: any-grade pneumonitis 3% vs 18%
Other: fracture 12% vs 2%
Cardiovascular: hypertension 34% vs 8%
Renal: proteinuria 54% vs 7%
Skin/nail: paronychia 66% vs 45%; acneiform rash 41% vs 20%
Bleeding: epistaxis 36% vs 8%
GI: nausea 25% vs 8%
Ocular: conjunctivitis 12% vs 2%
Pulmonary: any-grade pneumonitis 3% vs 18%
Other: fracture 12% vs 2%
Conclusions
Adding ramucirumab to osimertinib did not significantly improve PFS first-line in EGFR-mutant NSCLC; the primary endpoint was not met and toxicity was increased.
Key Limitations
Negative phase II (PFS not met); small N=122; OS immature; increased VEGF-related toxicity (hypertension, proteinuria); not powered for definitive conclusions.
Clinical Context
Does not support adding ramucirumab to osimertinib first-line. ESMO/ASCO endorse osimertinib monotherapy (or, per FLAURA2, osimertinib + chemotherapy) as preferred first-line; EGFR+VEGF combinations remain PFS-only without OS benefit.