Niraparib and dostarlimab plus radiotherapy (RT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients (TTCC-2022-01 RADIAN)

RADIAN

Paziente / Popolazione Intervento / Esposizione Confronto Esito

In patients with locally advanced head and neck squamous cell carcinoma fit for cisplatin chemoradiotherapy, niraparib and dostarlimab added to chemoradiotherapy improved 1-year disease-free survival against historical data, but in cisplatin-unfit patients given radiotherapy alone it increased toxicity without a disease-free survival benefit.

N

34pazienti

Disegno

Non-randomised two-cohort study in PD-L1 CPS>1, stage III-IVB HNSCC with ECOG 0-1: cohort A (candidates for cisplatin chemoradiotherapy) received one dose of dostarlimab at week -3 and niraparib from week -2 until the start of chemoradiotherapy, with no study drug during chemoradiotherapy, while cohort B (unfit for cisplatin) received one dose of dostarlimab at week -3 and niraparib continuously until the end of radiotherapy alone, and both cohorts then received dostarlimab plus niraparib maintenance from 4 weeks after radiotherapy for up to 14 cycles (Eu-CT 2024-516779-33-00; NCT05784012).

Esito

1-year disease-free survival against historical controls (expected HR <0.64; one-sided alpha <0.10).

RisultatoCohort A met the primary endpoint: 1-year DFS 88.2% (95% CI 74.2-100) vs 65% historical (HR 0.19, P = 0.01). Cohort B missed the primary endpoint: 1-year DFS 61% (95% CI 40-91) vs 55% historical (HR 0.72, P = 0.19), above the one-sided alpha of 0.10. Post-radiotherapy ORR was 93% (13 CR, 1 PR) in 15/17 evaluable patients in cohort A and 100% (11 CR, 4 PR) in 15/17 in cohort B. In cohort A, 2 patients died during chemoradiotherapy from adverse events (1 related to niraparib), and at a median follow-up of 17 months all 15 remaining patients were alive with no recurrence. In cohort B, grade >3 treatment-related adverse events occurred in all patients, 4 patients recurred and 5 died (2 related to niraparib-radiotherapy, 1 unrelated adverse event, 2 progression). Dostarlimab and/or niraparib were discontinued for treatment-related adverse events in 41% of cohort A vs 59% of cohort B.

Oliva M, Sepulveda ZV, Cirauqui BC, et al. Presented at ESMO Congress 2026, abstract LBA46, 25 October. Not yet published.

Discussione e critica

This small non-randomised study of 17 patients per cohort compares 1-year disease-free survival with historical rates rather than a concurrent control, and it uses a lenient one-sided alpha of 0.10, so cohort A's positive result shows a signal and does not prove benefit. In cohort A the study drugs were given only before chemoradiotherapy and as maintenance, which makes it hard to know what they added to standard treatment. Follow-up is short (median 17 months in cohort A and 13.6 months in cohort B), overall survival is not reported and the abstract does not describe the historical comparators. Cohort B's two toxic deaths and universal grade >3 toxicity, with no disease-free survival benefit, argue against giving niraparib alongside radiotherapy alone in cisplatin-unfit patients.