KEY POINTS
- NCT03574324 was a multicenter phase III randomized trial conducted at four Chinese institutions. 266 patients aged 18–69 years with newly diagnosed stage III–IVa non-keratinizing nasopharyngeal carcinoma were randomized 1:1 to induction chemotherapy followed by CCRT or CCRT followed by adjuvant chemotherapy.
- The induction group received three 21-day cycles of TPF—docetaxel 75 mg/m², cisplatin 75 mg/m² and fluorouracil 750 mg/m²/day for five days—followed by concurrent cisplatin and IMRT. The adjuvant group received the same CCRT followed by three cycles of cisplatin 80 mg/m² plus fluorouracil 800 mg/m²/day.
- Definitive IMRT prescribed up to 72.6 Gy in 33 fractions for T3–4 primary disease, 69.96 Gy in 33 fractions to other gross primary/nodal targets, 60.06 Gy to high-risk elective regions and 50.96 Gy in 28 fractions to lower-risk nodal regions. 264 of 266 patients completed radiotherapy, and median treatment duration was 50 days.
- At median follow-up of 39 months, the primary endpoint was negative: three-year progression-free survival was 79.0% with induction TPF versus 74.5% with adjuvant PF, HR 0.83 (95% CI 0.52–1.34; p=0.454). Per-protocol results were similarly negative at 79.9% versus 77.5% (p=0.717).
- No significant overall differences emerged for secondary survival outcomes. Three-year overall survival was 84.5% versus 81.7% (p=0.475), locoregional relapse-free survival 93.2% versus 93.5% (p=0.924) and distant metastasis-free survival 84.5% versus 78.4% (p=0.348).
- A prespecified-looking but subgroup-level signal emerged among baseline EBV-DNA-positive patients, where three-year PFS was 89.3% with induction versus 71.9% with adjuvant therapy (p=0.034). Other stage and risk subgroup analyses did not show significant treatment interactions, making this finding hypothesis-generating rather than definitive.
- Toxicity differed substantially by sequence. Grade 3–4 leukopenia occurred in 44.3% versus 21.9% and neutropenia in 59.5% versus 18.8%, favoring adjuvant PF. During CCRT, however, induction-treated patients reported less nausea/vomiting (77.1% vs 89.1%), swallowing toxicity (30.5% vs 43.8%) and xerostomia (44.3% vs 67.2%); no treatment-related deaths occurred.
CLINICAL TAKEAWAY
Induction TPF followed by CCRT did not demonstrate superior progression-free or overall survival compared with CCRT followed by PF in this phase III trial. Treatment sequencing may therefore be driven partly by tolerability and patient characteristics: induction produced more severe marrow toxicity but less symptomatic toxicity during radiation. The EBV-DNA-positive subgroup signal warrants confirmation rather than immediate treatment selection.