A prospective, randomized, phase II study of perioperative tislelizumab with chemotherapy in patients with locally advanced resectable oral squamous cell carcinoma (OPTIMAL study)

OPTIMAL

Patient / Population Intervention / Exposure Comparison Outcome

In patients with resectable locally advanced oral squamous cell carcinoma, neoadjuvant tislelizumab with chemotherapy followed by response-adapted, radiotherapy-free adjuvant tislelizumab has not yet been shown to improve 2-year event-free survival compared with surgery followed by standard postoperative radiotherapy or chemoradiotherapy.

N

116patients

Design

Prospective, randomised 1:1, phase II trial stratified by stage (III or IVa) in patients with resectable locally advanced oral squamous cell carcinoma, comparing three cycles of neoadjuvant tislelizumab with albumin-bound paclitaxel and cisplatin followed by surgery and response-adapted adjuvant therapy (six cycles of adjuvant tislelizumab without radiotherapy for patients with major pathological response and no positive margins or ENE, standard postoperative RT or CRT for the rest) with surgery followed by standard postoperative RT or CRT (NCT06470217).

Endpoint

2-year event-free survival.

ResultNo 2-year EFS rate or hazard ratio was reported. In the experimental arm, 9 EFS events occurred in the neoadjuvant plus radiotherapy subgroup (3 with PD during the neoadjuvant stage, 5 relapses and 1 death from radiotherapy complications; 3 deaths) and 2 EFS events (0 deaths) in the radiotherapy-free subgroup. The control group had 19 EFS events, including 8 deaths. In the experimental arm, ORR was 81.03% (47/58). Among the 55 patients who had surgery, the MPR rate was 65.45% (35/55) and the pCR rate was 45.45% (25/55). Grade ≥3 TRAEs occurred in 25.9% in the experimental arm vs 36.2% in the control group.

He Y, Houyu J, Ren G, et al. Presented at ESMO Congress 2026, abstract LBA47, 25 October. Not yet published.

Discussion & critique

This is an interim report of a 116-patient randomised phase II trial. The primary endpoint, 2-year EFS, is given only as raw event counts, with no rate, hazard ratio, confidence interval or P value, so efficacy cannot yet be judged. The abstract does not report blinding, follow-up duration or the number of patients randomised to each arm. Event counts are split across subgroups that were defined after randomisation by pathological response. The ORR, MPR and pCR figures exist only for the experimental arm because the control arm had no neoadjuvant therapy, and the lower rate of grade ≥3 TRAEs comes with no statistical test, so the case for omitting radiotherapy in responders is still a hypothesis.