Neoadjuvant with low-dose radiotherapy, tislelizumab, albumin-bound paclitaxel, and cisplatin for resectable locally advanced head and neck squamous cell carcinoma: phase II single-arm trial
Mené sur 28 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade III-IVB et non traité, cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse complète, d'un traitement néoadjuvant combinant une radiothérapie à faible dose de rayonnements, une immunothérapie par tislélizumab et une chimiothérapie par nab-paclitaxel et cisplatine
Although pathological complete response (pCR) and major pathological response (MPR) rates of neoadjuvant immunotherapy combined with chemotherapy in head and neck squamous cell carcinoma (HNSCC) trials remain suboptimal, emerging evidence highlights the synergistic potential of combining low-dose radiotherapy with immunotherapy to promote the efficacy of immunotherapy. This phase II, open-label, single-arm, multicenter trial (NCT05343325) enrolled 28 patients with untreated stage III-IVB HNSCC (NeoRTPC02). Patients received neoadjuvant low-dose radiotherapy, the programmed death-1 (PD-1) inhibitor tislelizumab, albumin-bound paclitaxel, and cisplatin for two cycles, followed by radical resection ~4 weeks after treatment completion. The primary endpoint, pCR rate, was achieved in 14 of 23 patients (60.9%; 23/28, 82.1% of the total cohort underwent surgery). Secondary endpoints included MPR rate (21.7%, 5/23), R0 resection rate (100%), and objective response rate (64.3%; 18/28). Treatment-related adverse events were manageable, with grade 3 or 4 treatment-related adverse events occurring in 10 (35.7%) patients. No surgical delays were observed. Single-cell RNA sequencing revealed remodeling of the HNSCC tumor microenvironment, which may correlate with improved clinical outcomes. This trial met the pre-specified primary endpoint, demonstrating a high pCR rate with promising efficacy and manageable toxicity in locally advanced HNSCC.
Nature Communications , article en libre accès, 2025