Results from a phase II trial, presented by Sehhoon Park at ESMO 2026, demonstrated promising clinical and pathological responses with neoadjuvant nivolumab, docetaxel, and cisplatin followed by surgery and risk-adapted radiotherapy in patients with resectable, high-grade salivary gland cancer and clinically positive lymph nodes.
Among patients who underwent surgery, 60.9% achieved a major pathologic response (MPR), while 32.6% achieved a pathologic complete response (pCR), exceeding the study’s predefined efficacy threshold.
The findings suggest that neoadjuvant chemoimmunotherapy may offer a promising treatment approach for this aggressive and relatively rare malignancy.
Background
High-grade salivary gland carcinoma is an aggressive group of head and neck cancers associated with substantial risks of recurrence and distant metastases. Patients with clinically positive lymph nodes are particularly vulnerable to distant disease progression, even following curative surgery and adjuvant radiotherapy.
Although surgery followed by risk-adapted radiotherapy remains a central component of treatment, effective neoadjuvant systemic strategies have not been established. The phase II study evaluated whether combining the PD-1 inhibitor nivolumab with docetaxel and cisplatin could improve tumor response before surgery and potentially influence longer-term outcomes.
Study Design and Patient Population
This was a single-center, single-arm phase II trial involving treatment-naïve patients with resectable, high-grade salivary gland carcinoma and clinically positive lymph nodes.
A total of 55 patients were enrolled. After excluding four screening failures and one patient with benign histology, 50 patients were included in the analysis. The median age was 62 years, and 88% were male. Most patients had an ECOG performance status of 1.
According to AJCC eighth edition staging, 34% had stage III disease, 64% had stage IVA, and 2% had stage IVB. Salivary duct carcinoma was the predominant histological subtype, accounting for 74% of patients, followed by adenocarcinoma (10%) and mucoepidermoid carcinoma (8%).
Patients received three cycles of neoadjuvant treatment every three weeks, consisting of:
Nivolumab: 360 mg intravenously.
- Docetaxel: 60 mg/m².
- Cisplatin: 60 mg/m².
Following neoadjuvant treatment, patients were scheduled to undergo curative surgery followed by risk-adapted adjuvant radiotherapy.
The primary endpoint was major pathologic response, defined as 10% or less residual viable tumor in the surgical specimen.
Clinical and Pathologic Response Results
The neoadjuvant combination demonstrated substantial antitumor activity. The objective response rate (ORR) was 52.0% among the 50 analyzed patients. Of these, 46 patients (92.0%) proceeded to surgery.
Four patients did not undergo surgery because of withdrawal (one patient), disease progression (two patients), or grade 3 drug-induced pneumonitis (one patient).
Among the 46 patients who underwent resection:
- Major pathologic response: 60.9% (28 patients).
- Pathologic complete response: 32.6% (15 patients).
- R0 resection rate: 93.5%.
The MPR rate exceeded the study’s predefined efficacy threshold of 50%, meeting its primary response criterion.
These findings suggest that a substantial proportion of patients experienced marked tumor regression following neoadjuvant nivolumab and chemotherapy.
Responses Across Histological Subtypes
Pathologic responses differed across salivary gland carcinoma subtypes.
The highest reported major pathologic response rates were observed in:
- Salivary duct carcinoma: MPR 67.6%, pCR 29.4%.
- Adenocarcinoma: MPR 75.0%, pCR 75.0%.
- Poorly differentiated carcinoma: MPR 66.7%, pCR 66.7%.
Although these results are encouraging, the small numbers of patients within individual histological subgroups limit conclusions about differences in treatment sensitivity. The predominance of salivary duct carcinoma in the study population should also be considered when interpreting the overall findings.
Disease-Free and Overall Survival
At a median follow-up of 16.2 months from surgery, the study reported encouraging early survival outcomes.
Disease-free survival (DFS) rates were:
- 12 months: 89.0%.
- 24 months: 76.0%.
The 24-month overall survival rate was 91.2%.
Importantly, achieving a major pathologic response was associated with significantly longer disease-free survival. Median DFS was not reached among patients with MPR, compared with 24.2 months among those without MPR.
The hazard ratio was 0.19 (95% CI, 0.05–0.71; P=0.013).
This association suggests that major pathologic response may be an important indicator of subsequent disease control in patients receiving neoadjuvant chemoimmunotherapy. However, longer follow-up is needed to determine whether pathologic response translates into sustained survival benefits.
Safety and Treatment Tolerability
The neoadjuvant regimen demonstrated a generally manageable safety profile in the study population. Most treatment-related adverse events were grade 1 or 2.Six grade 3 or higher treatment-related adverse events were reported, all described as manageable.
No treatment-related deaths occurred.
However, one patient was unable to proceed to surgery because of grade 3 drug-induced pneumonitis, highlighting the importance of monitoring for serious treatment-related complications. The findings suggest that neoadjuvant nivolumab combined with docetaxel and cisplatin may be feasible before definitive local treatment, although further safety evaluation is required.
Conclusion
The phase II trial demonstrated promising pathologic responses with neoadjuvant nivolumab, docetaxel, and cisplatin followed by surgery and risk-adapted radiotherapy in patients with resectable, node-positive, high-grade salivary gland carcinoma.
Major pathologic response was achieved in 60.9% of operated patients, while 32.6% achieved a pathologic complete response.
Two-year disease-free survival reached 76.0%, and patients achieving MPR experienced significantly better disease-free survival than those without MPR.
Although these early findings support further investigation of neoadjuvant chemoimmunotherapy, randomized studies are needed before the regimen can be considered an established treatment strategy in this population.
