Editor's Note: Neoadjuvant treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) must achieve tumor regression and improve the likelihood of surgery while minimizing the impact on organ function and quality of life. At the 2026 European Society for Medical Oncology (ESMO) Congress, preliminary results were reported from an exploratory study evaluating neoadjuvant iparomlimab and tovoricimab (hereafter referred to as the “combination antibody regimen”) plus nab-paclitaxel and nedaplatin. As of April 2026, 12 patients had been enrolled. The cohort included a relatively high proportion of patients with hypopharyngeal cancer, and most patients had a PD-L1 combined positive score (CPS) of less than 20. The study reported high objective response and pathological response rates. However, this was a small, single-arm exploratory study, and the findings require validation through controlled studies and long-term follow-up. Oncology Frontier interviewed Professor Wei Xu about the study design, interpretation of pathological response, appropriate patient populations, and functional outcomes.Promising Early Results from Neoadjuvant Treatment for Locally Advanced Head and Neck Squamous Cell Carcinoma
Oncology Frontier: In a cohort of patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC), which included a relatively high proportion of patients with low PD-L1 expression and hypopharyngeal cancer, the combination antibody regimen plus chemotherapy achieved high objective response and pathological response rates. How would you interpret these findings in the context of current neoadjuvant treatment research?
Professor Wei Xu: When evaluating a neoadjuvant regimen in clinical practice, two questions should come first: Can the tumor shrink sufficiently before surgery, and can the patient proceed to surgery as planned? For patients with locally advanced head and neck squamous cell carcinoma, the treatment goals go beyond radiographic tumor shrinkage. They also include improving the possibility of surgical resection, reducing surgical complexity, and creating conditions that may facilitate organ preservation. Preoperative treatment must also avoid delaying surgery or increasing perioperative risks.
The study enrolled patients with locally advanced disease who had not previously received systemic treatment, with staging defined according to the eighth edition of the AJCC classification as T2–4aN0–3M0. Patients received the combination antibody regimen (5 mg/kg once every three weeks) plus nab-paclitaxel (260 mg/m²) and nedaplatin (80 mg/m²) for two cycles. Surgery was scheduled three to six weeks after completion of treatment. This design kept the neoadjuvant treatment period relatively short, followed by surgical evaluation.
As of April 2026, 12 patients had been enrolled. Hypopharyngeal cancer accounted for 58.3% of the cohort, and 66.7% of patients had a PD-L1 CPS of less than 20. The reported objective response rate (ORR) was 100% (12/12), including a complete response (CR) rate of 50% (6/12). Among the nine patients who underwent surgery, the pathological complete response (pCR) rate was 55.6% (5/9), and the major pathological response (MPR) rate was 100% (9/9). In this cohort of previously untreated patients with locally advanced disease and a relatively high proportion of hypopharyngeal cancer, the study observed a high preoperative response rate.
However, the study included only 12 patients and was a single-arm exploratory investigation. At this stage, these findings cannot establish that the combination antibody regimen plus chemotherapy is superior to other neoadjuvant approaches, nor should its response rates be directly compared with those reported in different studies. Further research involving larger patient populations is needed to validate its efficacy and assess its impact on surgical feasibility and long-term disease control.
From Pathological Response to Survival Benefit: The Pursuit of Better Outcomes Continues
Oncology Frontier: The study reported relatively high pCR and MPR rates. How should clinicians understand the relationship between pathological response and long-term patient benefit? Which endpoints should be prioritized in subsequent follow-up?
Professor Wei Xu: pCR and MPR reflect changes in residual tumor burden following neoadjuvant treatment and are important early pathological evaluation indicators. A deeper pathological response may indicate a reduction in tumor burden and could potentially contribute to improved local control and subsequent treatment outcomes. However, these indicators cannot replace survival endpoints, nor can they independently demonstrate that patients will achieve longer survival. The prognosis of head and neck squamous cell carcinoma is also influenced by multiple factors, including the primary tumor site, T and N stage, resection margin status, residual lymph node disease, postoperative treatment, recurrence and metastasis, and HPV status.
In this study, the nine patients who underwent surgery had an MPR rate of 100% and a pCR rate of 55.6%. At present, these findings demonstrate a pathological response signal, but they cannot establish long-term clinical benefit. Whether the regimen improves event-free survival (EFS), progression-free survival (PFS), or overall survival (OS) remains to be determined through further follow-up.
Subsequent assessments should first examine whether surgery can be performed as planned, including the R0 resection rate, extent of resection, perioperative complications, and postoperative recovery. Patients should also be followed for locoregional recurrence, distant metastasis, EFS, PFS, and OS.
For head and neck tumors, laryngeal function, swallowing, nutritional status, rehabilitation progress, and patient-reported quality of life are equally important. The treatment goal is not simply to control the tumor, but also to preserve, as much as possible, patients’ ability to eat, swallow, and communicate. These are treatment outcomes that patients can directly experience in their daily lives.
Oncology Frontier: There is currently no universally accepted optimal neoadjuvant regimen for locally advanced head and neck squamous cell carcinoma. Considering the efficacy and safety findings of this study, which patients would be suitable for inclusion in subsequent research? What evidence is still needed before this approach can enter clinical practice?
Professor Wei Xu: Based on the eligibility criteria of this study, subsequent research could prioritize patients with good performance status who have not previously received treatment, have locally advanced disease, and have a clearly defined surgical objective following multidisciplinary evaluation. The original study enrolled patients aged 18–75 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 and T2–4aN0–3M0 disease.
Suitability for neoadjuvant treatment cannot be determined by disease stage alone. The multidisciplinary team, including head and neck surgeons, medical oncologists, and radiation oncologists, must jointly assess whether patients can tolerate the regimen, whether the timing of surgery can be controlled, and whether a reasonable pathway to definitive local treatment will remain available after neoadjuvant therapy.
In this study, 66.7% of patients had a CPS of less than 20, indicating that the cohort included a relatively high proportion of patients with low PD-L1 expression. However, the current sample size is insufficient to demonstrate that this subgroup derives greater benefit. The combination antibody regimen targets both the PD-1 and CTLA-4 pathways, providing a mechanistic hypothesis for further investigation. To identify which patients are most likely to benefit, larger studies should incorporate analyses based on CPS, primary tumor site, TNM stage, HPV status, and tumor immune characteristics.
Safety must be evaluated in the specific context of preoperative treatment. Among the 12 patients, the incidence of treatment-related adverse events was 83.3%, while grade ≥3 treatment-related adverse events occurred in 25.0%. The incidence of immune-related adverse events was 25.0%, with grade ≥3 events occurring in 8.3%; rash was the predominant event. Myelosuppression occurred in 58.3% of patients, with grade ≥3 events reported in 25.0%. No treatment-related deaths were reported.
The toxicities observed in this study appear manageable, but the small sample size is insufficient to fully characterize the risk profile. Subsequent studies should also report the timing of adverse events, management strategies, whether surgery was delayed, perioperative complications, and the continuity of postoperative adjuvant treatment.
Balancing Tumor Control and Functional Preservation: Toward a Comprehensive Neoadjuvant Treatment Strategy
Oncology Frontier: Treatment of head and neck tumors must balance tumor control with preservation of organ function. How should future neoadjuvant studies incorporate patients’ quality of life and treatment burden into their evaluation?
Professor Wei Xu: Treatment for head and neck tumors can directly affect swallowing, speech, nutrition, and appearance. Therefore, the evaluation of neoadjuvant treatment should not focus solely on the extent of tumor shrinkage. An improvement in response rates is important; however, if treatment causes substantial toxicity, increases surgical complications, or results in long-term impairment of swallowing and speech, the overall benefit must be reassessed.
In addition to ORR, pCR, and survival endpoints, future studies should prospectively incorporate assessments of organ function, swallowing and laryngeal function, nutritional status, patient-reported quality of life, rehabilitation outcomes, and treatment-related adverse events. Stable and comparable assessment tools should be used throughout follow-up. Patients’ baseline swallowing, speech, and nutritional status should be documented before treatment so that subsequent changes can be evaluated and potentially attributed to treatment.
This requires close collaboration among multidisciplinary teams. The surgical team should assess resectability and the potential for functional preservation; medical oncology and radiation oncology teams should coordinate systemic and local treatment; and nutrition and rehabilitation teams should participate in management during treatment and after surgery. The evaluation of neoadjuvant treatment must consider not only whether the tumor regresses, but also whether patients can achieve reliable disease control and retain as much of their daily functioning as possible after treatment.
Encouraging Early Signals Point to a Promising Future for Neoadjuvant Treatment in Head and Neck Squamous Cell Carcinoma
This study investigated the combination antibody regimen plus chemotherapy as neoadjuvant treatment for locally advanced head and neck squamous cell carcinoma. While exploring preoperative tumor regression, it also raised an important clinical question: How can patients proceed to subsequent surgery without disruption while preserving functions such as swallowing and speech to the greatest extent possible?
The pathological response signals observed in this study provide a rationale for further investigation of this treatment strategy. However, the current findings are derived from a small, single-arm study and cannot establish that the regimen is superior to other treatments. Nor can long-term survival or functional benefits be inferred from pathological response alone.
Larger studies, appropriate controlled comparisons, and long-term follow-up are still needed to clarify efficacy and safety, as well as to assess the effects of preoperative treatment on surgical timing, resection outcomes, and perioperative recovery. In addition to locoregional recurrence, distant metastasis, and survival outcomes, assessments of swallowing and laryngeal function, nutritional status, and patient-reported quality of life should also be incorporated. As evidence accumulates regarding factors such as PD-L1 expression, primary tumor site, and HPV status, clinicians may gain a clearer understanding of which patients are suitable for this approach, providing a stronger basis for individualized treatment.
