Background
Phase 3, multicenter, double-blind, placebo-controlled RCT including 289 patients with untreated recurrent or metastatic nasopharyngeal carcinoma. Evaluated adding the anti-PD-1 antibody toripalimab to first-line gemcitabine/cisplatin.
Interventions and follow up
Arm A: Toripalimab 240 mg + gemcitabine 1 g/m2 D1,8 + cisplatin 80 mg/m2 D1 every 3 weeks x6, then toripalimab maintenance every 3 weeks
Arm B: Placebo + gemcitabine 1 g/m2 D1,8 + cisplatin 80 mg/m2 D1
Primary endpoint: PFS by BIRC
Secondary endpoints: ORR, DoR, OS, safety
mFollow up: 17.9 mo (primary); 30.1 mo (final OS)
Arm B: Placebo + gemcitabine 1 g/m2 D1,8 + cisplatin 80 mg/m2 D1
Primary endpoint: PFS by BIRC
Secondary endpoints: ORR, DoR, OS, safety
mFollow up: 17.9 mo (primary); 30.1 mo (final OS)
Results
mPFS: 11.7 mo vs 8.0 mo; HR 0.52, 95%CI 0.36-0.74, P=.0003
ORR: 77.4% vs 66.4%, P=.04
1-yr OS: 91.6% vs 87.1%
2-yr OS: 77.8% vs 63.3%
Final OS: NR vs 33.7 mo; HR 0.63, 95%CI 0.45-0.89, P=.008
ORR: 77.4% vs 66.4%, P=.04
1-yr OS: 91.6% vs 87.1%
2-yr OS: 77.8% vs 63.3%
Final OS: NR vs 33.7 mo; HR 0.63, 95%CI 0.45-0.89, P=.008
Adverse events
Overall grade 3-4: 89.0% vs 89.5%; largely chemotherapy-related and similar between arms
Hematologic: leukopenia 61% vs 58%, anemia 47% vs 40%, thrombocytopenia 32% vs 28%
Immune-related: irAEs in 7.5% (grade ≥3); hypothyroidism and pneumonitis most notable
Hematologic: leukopenia 61% vs 58%, anemia 47% vs 40%, thrombocytopenia 32% vs 28%
Immune-related: irAEs in 7.5% (grade ≥3); hypothyroidism and pneumonitis most notable
Conclusions
Adding toripalimab to first-line gemcitabine/cisplatin significantly improved PFS and OS in recurrent or metastatic nasopharyngeal carcinoma without adding substantial chemotherapy-related toxicity, establishing chemoimmunotherapy as a first-line standard.
Key Limitations
Population almost entirely Chinese with endemic EBV-associated disease, limiting generalizability. Crossover and post-progression immunotherapy may confound OS interpretation.
Clinical Context
Supported FDA approval (Oct 2023) of toripalimab with gemcitabine/cisplatin for first-line recurrent/metastatic nasopharyngeal carcinoma; ESMO endorses PD-1 inhibitor plus gemcitabine/cisplatin as a preferred first-line regimen.
References