Background
Phase III double-blind RCT, N=1,253, stage IV NSCLC (squamous and nonsquamous) with progression on/after first-line platinum-based chemotherapy.
Interventions and follow up
Arm A: Docetaxel 75 mg/m2 q3wk + ramucirumab 10 mg/kg q3wk
Arm B: Docetaxel 75 mg/m2 q3wk + placebo
Primary endpoint: OS
Arm B: Docetaxel 75 mg/m2 q3wk + placebo
Primary endpoint: OS
Results
mOS: 10.5 vs 9.1 mo (A vs B); HR 0.86, 95%CI 0.75-0.98; P=.023
mPFS: 4.5 vs 3.0 mo; HR 0.76, 95%CI 0.68-0.86; P<.0001
ORR: 23% vs 14%; P<.0001
mPFS: 4.5 vs 3.0 mo; HR 0.76, 95%CI 0.68-0.86; P<.0001
ORR: 23% vs 14%; P<.0001
Adverse events
Overall (A vs B): grade ≥3 79% vs 72%
Hematologic gr≥3: neutropenia 49% vs 40%; febrile neutropenia 16% vs 10%; leukopenia 14% vs 12%
Constitutional gr≥3: fatigue 14% vs 10%
Vascular: hypertension gr≥3 6% vs 2%; bleeding (mostly gr1-2) 29% vs 15%
Antiangiogenic class effects: wound dehiscence, arterial thrombosis, GI perforation, RPLS, hypothyroidism, infusion reactions (esp early cycles)
Hematologic gr≥3: neutropenia 49% vs 40%; febrile neutropenia 16% vs 10%; leukopenia 14% vs 12%
Constitutional gr≥3: fatigue 14% vs 10%
Vascular: hypertension gr≥3 6% vs 2%; bleeding (mostly gr1-2) 29% vs 15%
Antiangiogenic class effects: wound dehiscence, arterial thrombosis, GI perforation, RPLS, hypothyroidism, infusion reactions (esp early cycles)
Conclusions
Adding ramucirumab to docetaxel modestly improved OS and PFS as second-line therapy in advanced NSCLC; reasonable for patients with robust performance status.
Key Limitations
Modest absolute OS gain (1.4 mo) with added toxicity and cost. Predates routine first-line immunotherapy, so the second-line landscape has shifted; limited role after modern chemo-IO. No biomarker selection.
Clinical Context
FDA approved ramucirumab + docetaxel for metastatic NSCLC progressing on platinum chemotherapy (Dec 2014), including squamous histology. ESMO lists docetaxel +/- ramucirumab/nintedanib as second-line chemotherapy options after immunotherapy exhaustion.