Background
Open-label, multicentre, phase 3 noninferiority RCT (ConCERT; India, AIIMS-led). N=278 enrolled (272 evaluable). Non-nasopharyngeal locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Compares weekly low-dose vs 3-weekly high-dose cisplatin with definitive 70 Gy radiotherapy.
Results
INTERVENTIONS AND FOLLOW UP: Arm A: cisplatin 40 mg/m² weekly + 70 Gy RT (n=141).
Arm B: cisplatin 100 mg/m² Q3W + 70 Gy RT (n=137).
Primary endpoint: 2-year locoregional control (LRC); noninferiority margin −10%.
mFollow up: 43.9 months.
RESULTS: 2yr LRC: 61.3% (weekly) vs 51.1% (Q3W); absolute difference +10.2% (one-sided 95% CI lower bound 0.3%), within NI margin; HR 0.72, 95% CI 0.50–1.05, P=.091.
PFS: 20.3 vs 17.9 mo, P=.204.
OS: 24.9 vs 22.2 mo, P=.501.
Arm B: cisplatin 100 mg/m² Q3W + 70 Gy RT (n=137).
Primary endpoint: 2-year locoregional control (LRC); noninferiority margin −10%.
mFollow up: 43.9 months.
RESULTS: 2yr LRC: 61.3% (weekly) vs 51.1% (Q3W); absolute difference +10.2% (one-sided 95% CI lower bound 0.3%), within NI margin; HR 0.72, 95% CI 0.50–1.05, P=.091.
PFS: 20.3 vs 17.9 mo, P=.204.
OS: 24.9 vs 22.2 mo, P=.501.
Adverse events
Grade ≥3 (any): 44.7% (weekly) vs 60.7% (Q3W), P=.018.
Hospitalisation for toxicity: 20.3% vs 36.8%, P=.004.
Hospitalisation for toxicity: 20.3% vs 36.8%, P=.004.
Conclusions
Weekly low-dose cisplatin chemoradiation was noninferior to 3-weekly high-dose cisplatin for 2-year locoregional control in non-nasopharyngeal LA-HNSCC, with significantly less grade ≥3 toxicity and fewer hospitalisations. Supports weekly cisplatin as a viable definitive-CRT schedule.
Key Limitations
Open-label; conducted at Indian centres with most accrual at one institution; modest sample (N=278) for a noninferiority design; the LRC point estimate favoured weekly but the HR was not statistically significant (P=.091); the 10% noninferiority margin is relatively wide.
Clinical Context
High-dose 3-weekly cisplatin (100 mg/m²) with RT is the historical definitive-CRT standard for LA-HNSCC; weekly cisplatin is widely used for tolerability but randomised phase 3 data in the definitive (non-postoperative) setting are limited. ConCERT adds support for weekly cisplatin, consistent with NCCN and ASCO acceptance of both schedules. In the postoperative setting a prior trial favoured high-dose cisplatin, so schedule choice remains setting-dependent.