Editor's Note: Concurrent chemoradiotherapy remains the standard treatment for locally advanced cervical cancer. For high-risk patients with a substantial tumor burden, extensive local invasion, or lymph node metastases, rapidly reducing tumor burden early in treatment and creating favorable conditions for subsequent definitive therapy remain important clinical challenges.At the 2026 European Society for Medical Oncology (ESMO) Congress, interim results were presented from a prospective, single-arm exploratory study evaluating QL1706 plus chemotherapy as neoadjuvant treatment for locally advanced cervical cancer.
As of October 2026, 20 patients had been enrolled, of whom 14 had undergone surgery. Among the patients who completed surgery, more than 50% had stage III or IV disease, and 92.9% had squamous cell carcinoma. The objective response rate (ORR) was 100%, and the pathological response rate was 78.6%, including a pathological complete response (pCR) rate of 35.7% and a major pathological response (MPR) rate of 42.9%. The R0 resection rate was 93%.
The one-year event-free survival (EFS) rate among currently evaluable patients was 100%. However, only three patients were evaluable for this survival endpoint, and longer follow-up is required.
Oncology Frontier interviewed Professor Wei Sheng from Shandong Provincial Hospital, affiliated with Shandong First Medical University, to discuss the clinical rationale for introducing immunotherapy in the neoadjuvant setting and the key considerations regarding patient selection, toxicity management, and coordination with surgery.
Oncology Frontier: Concurrent chemoradiotherapy remains the standard treatment for locally advanced cervical cancer. For patients with a high tumor burden, extensive local invasion, or lymph node metastases, what clinical insights does the exploration of neoadjuvant QL1706 plus chemotherapy provide?
Professor Wei Sheng: Concurrent chemoradiotherapy remains the standard treatment for locally advanced cervical cancer, and this is the foundation of clinical decision-making.
In clinical practice, some patients present with large tumors, extensive local invasion, or lymph node metastases. Even after completing standard treatment, these patients may still face a relatively high risk of recurrence and metastasis. For this population, an important practical question is whether tumor burden can be reduced early in treatment to create more favorable conditions for subsequent definitive therapy.
Historically, studies of neoadjuvant chemotherapy alone in locally advanced cervical cancer have produced inconsistent findings, and its long-term survival benefits remain controversial. Therefore, neoadjuvant treatment should not simply be regarded as a replacement for concurrent chemoradiotherapy.
The rationale behind the current study was to add QL1706 to chemotherapy and introduce immunotherapy before surgery, evaluating whether this combination could achieve more substantial tumor regression and pathological response, followed by reassessment of surgical opportunities.
According to the interim results, as of October 2026, 20 patients had been enrolled, and 14 had completed surgery. Among those who underwent surgery, more than 50% had stage III or IV disease, and 92.9% had squamous cell carcinoma.
The ORR was 100%, and the pathological response rate was 78.6%, including a pCR rate of 35.7% and an MPR rate of 42.9%. The R0 resection rate was 93%.
The currently reported one-year EFS rate was 100%, but only three patients were evaluable for this endpoint. These findings therefore require validation through additional follow-up.
These data suggest that some patients with locally advanced disease may become candidates for surgical evaluation following neoadjuvant combination treatment. They also indicate that introducing immunotherapy in the neoadjuvant setting warrants further investigation.
However, this is a small, single-arm exploratory study, and its findings are insufficient to justify changes to the current standard of care.
The next steps are to determine whether pathological responses translate into more durable event-free survival and long-term survival benefits, and to identify which patients are most likely to benefit from this treatment pathway.
Oncology Frontier: QL1706 simultaneously targets the PD-1 and CTLA-4 immune checkpoints. Why might combining this type of dual-functional antibody with chemotherapy in the neoadjuvant setting produce deeper pathological responses?
Professor Wei Sheng: Cervical cancer is closely associated with human papillomavirus (HPV) infection, and the tumor itself has a degree of immunogenicity. This provides a biological rationale for moving immunotherapy into earlier lines of treatment and the perioperative setting.
The neoadjuvant setting also has a distinctive characteristic: the primary tumor has not yet been removed, meaning that a relatively intact source of tumor antigens remains in the body.
Chemotherapy can directly kill tumor cells and promote antigen release. Combining chemotherapy with immunotherapy may therefore, in theory, create greater opportunities to activate the body’s antitumor immune response.
A key characteristic of QL1706 is its ability to target both PD-1 and CTLA-4 immune checkpoints within a single molecule.
The PD-1 pathway is more closely associated with the function of already activated effector T cells, whereas CTLA-4 participates in T-cell priming and immune regulation.
By targeting both pathways within one molecule and combining this approach with chemotherapy, the study aims to investigate whether tumor regression, antigen release, and immune activation can work together more effectively.
This exploratory strategy is supported by previous research.
The DUBHE-C series of studies demonstrated antitumor activity and a manageable safety profile for QL1706 in recurrent or metastatic cervical cancer. In second-line and later treatment, the ORR was 33.3%, and the disease control rate (DCR) was 65.3%. First-line investigations also demonstrated relatively high response rates.
The purpose of extending this research into locally advanced disease and the neoadjuvant setting is to determine whether the efficacy signals previously observed in advanced disease can also be reproduced at an earlier treatment stage.
However, perioperative treatment cannot be evaluated solely on the basis of biological mechanisms and radiographic responses.
Three important clinical questions must also be addressed: Are the pathological responses sufficiently robust? Can patients successfully undergo surgery or return to the concurrent chemoradiotherapy pathway? And will treatment-related toxicity interfere with subsequent therapy?
Future analyses incorporating PD-L1 expression, HPV status, histological subtype, and characteristics of the tumor immune microenvironment may help identify patients who are more suitable for this approach.
At present, however, these remain research questions. Biological plausibility cannot be equated with established clinical benefit.
Oncology Frontier: The use of chemotherapy combined with a dual-functional antibody in the perioperative setting places greater demands on patient selection, toxicity monitoring, and coordination with surgery. Which aspects should be carefully evaluated in advance in clinical practice?
Professor Wei Sheng: One of the most important considerations in perioperative treatment is avoiding a situation in which intensive initial therapy prevents patients from proceeding smoothly to surgery or radiotherapy.
Therefore, the first step is appropriate patient selection.
Not every patient with locally advanced cervical cancer is suitable for a treatment pathway involving neoadjuvant immunotherapy plus chemotherapy followed by surgery.
Before treatment, clinicians should evaluate tumor extent, the degree of pelvic invasion, lymph node status, performance status, comorbidities, and organ function. They must also determine whether surgery could become feasible following neoadjuvant treatment.
Ideally, this assessment should be conducted before treatment begins by a multidisciplinary team involving gynecologic oncologic surgeons, medical oncologists, radiation oncologists, and radiologists.
During treatment, clinicians must monitor both chemotherapy-related toxicities and immune-related adverse events.
For chemotherapy, particular attention should be paid to myelosuppression, gastrointestinal reactions, and changes in liver and kidney function.
For immunotherapy, clinicians should monitor liver function abnormalities, endocrine disorders, rash, and other immune-related adverse events.
Updated data presented in the study slides showed that, among 14 patients, three experienced grade 3–4 neutropenia, corresponding to an incidence of 21.4%. One patient developed grade 3 liver function abnormalities and recovered following appropriate management.
As of October 2026, no treatment-related deaths, treatment delays, or perioperative complications had occurred.
These findings suggest that the regimen’s tolerability is generally acceptable at this stage. However, they also remind us that myelosuppression and liver function abnormalities must be addressed before they begin to interfere with the surgical schedule.
During every treatment cycle, clinical decisions should incorporate complete blood counts, liver and kidney function, symptoms, and performance status. Supportive treatment and subsequent dosing schedules should be adjusted promptly when necessary.
The final consideration is coordination with surgery.
Following neoadjuvant treatment, clinicians should not rely solely on radiographic tumor shrinkage. Gynecologic examination, imaging assessments, and relevant pathological information, when necessary, should also be considered to determine whether the patient is eligible for definitive surgery.
If the patient does not meet the criteria for surgery, treatment should promptly return to standard pathways, such as concurrent chemoradiotherapy.
For this emerging treatment strategy, treatment intensity is not the only objective.
The key is to establish clear treatment goals before therapy, manage toxicities effectively during treatment, and ensure a smooth transition to surgery or radiotherapy afterward.
Interim pathological response and R0 resection results can only be meaningfully linked to long-term patient benefit when considered alongside subsequent treatment and follow-up outcomes.
Professor Wei Sheng
