Background
Phase III, multicenter, randomized. N=480, locoregionally advanced NPC (AJCC/UICC stage III–IVb). China (Sun Yat-sen). IMRT backbone + concurrent cisplatin 100 mg/m² q3wk × 3 in both arms. Primary endpoint: failure-free survival.
Interventions and follow up
Arm A (induction GC + CRT): gemcitabine 1000 mg/m² d1,8 + cisplatin 80 mg/m² d1 q3wk × 3, then concurrent cisplatin 100 mg/m² q3wk × 3 + IMRT
Arm B (CRT alone, control): concurrent cisplatin 100 mg/m² q3wk × 3 + IMRT
Primary endpoint: failure-free survival (FFS)
mFollow up: 39.0 mo (primary); 69.8 mo (JCO 2022 final)
Arm B (CRT alone, control): concurrent cisplatin 100 mg/m² q3wk × 3 + IMRT
Primary endpoint: failure-free survival (FFS)
mFollow up: 39.0 mo (primary); 69.8 mo (JCO 2022 final)
Results
3-yr FFS: 85.3% vs 76.5%, HR 0.51 (95% CI 0.34–0.77), P<.001
3-yr OS: 94.6% vs 90.3%, HR 0.43 (95% CI 0.24–0.77), P=.004
5-yr OS (final): 87.9% vs 78.8%, HR 0.51, P=.001
Distant failure: significantly lower with induction GC
3-yr OS: 94.6% vs 90.3%, HR 0.43 (95% CI 0.24–0.77), P=.004
5-yr OS (final): 87.9% vs 78.8%, HR 0.51, P=.001
Distant failure: significantly lower with induction GC
Adverse events
Induction grade ≥3: neutropenia 27.9%, thrombocytopenia 11.6%, anemia 4.4%
Late grade ≥3: 11.3% vs 11.4% (NS)
Induction compliance: 95.8% completed all 3 GC cycles
Note: no excess radiation-related toxicity with combined approach
Late grade ≥3: 11.3% vs 11.4% (NS)
Induction compliance: 95.8% completed all 3 GC cycles
Note: no excess radiation-related toxicity with combined approach
Conclusions
Induction gemcitabine-cisplatin before concurrent CRT significantly improved FFS and OS in locoregionally advanced NPC, with ~9% 5-yr OS benefit and acceptable toxicity; established induction GC as a standard.
Key Limitations
Single-country (China), endemic NPC — generalizability to non-endemic disease uncertain; open-label; FFS surrogate; added induction toxicity and logistics.
Clinical Context
One of several positive induction-chemo NPC trials supporting induction + concurrent CRT for high-risk locoregionally advanced disease; gemcitabine-cisplatin is a favored induction regimen.