These estimates came with wide confidence intervals and the trial stopped after enrolling 16 of its planned 30 participants because of slow accrual, so the findings require cautious interpretation and confirmation in randomized studies. The trial enrolled adults with histologically confirmed recurrent or metastatic squamous cell carcinoma arising in the oral cavity, oropharynx, larynx or hypopharynx. Disease was not amenable to curative surgery or radiotherapy, and participants had not received systemic therapy for recurrent or metastatic disease.

Other eligibility requirements included at least one measurable lesion under Response Evaluation Criteria in Solid Tumors version 1.1, an Eastern Cooperative Oncology Group performance status of 0 or 1, an estimated life expectancy of at least six months and adequate organ function. Patients were excluded if they had previously received PD-1, PD-L1 or CTLA-4 inhibitors, or if they had active autoimmune disease, another malignancy within two years, systemic immunosuppression, symptomatic central nervous system metastases or active infection. Treatment had an induction phase consisting of intravenous cadonilimab at 10 mg per kilogram on day one, combined every three weeks with platinum and 5-fluorouracil, or PF, chemotherapy for four to six cycles.

Cisplatin was administered at 80 mg per square meter on days one through three, while carboplatin was given at an area under the curve target of five on day one. Each regimen also included a continuous infusion of 5-fluorouracil at 1,000 mg per square meter per day for four days. Patients without progression or unacceptable toxicity then continued cadonilimab alone every three weeks until progression, unacceptable toxicity or withdrawal of consent.

All 16 participants received induction treatment for a median of five cycles, ranging from two to six, and 10 transitioned to maintenance cadonilimab. Six patients stopped during induction, four because of disease progression and two because of patient decision or treatment fatigue. Of the 10 who entered maintenance, seven later discontinued because of progression, one because of patient decision or fatigue and two remained on treatment with ongoing responses at the data cutoff.

The enrolled group had a median age of 59.5 years, ranging from 47 to 71, and 14 participants were male. Most patients had a favorable performance status, with 12 of 16 scoring ECOG 0, while four scored ECOG 1. The oropharynx was the most common primary site, accounting for six patients, followed by the oral cavity with five, larynx with three and hypopharynx with two.

Eight patients had local recurrence, six had regional lymph-node recurrence and four had distant metastasis; some categories overlapped, so their cumulative percentages exceeded 100%. Three of the six patients with oropharyngeal tumors were p16 positive. PD-L1 combined positive scores were at least 20 in six patients, between 1 and 19 in four and below 1 in five, with one result unavailable.

The cohort also had relatively favorable prognostic features, including a high proportion with ECOG 0, p16 positivity among half of patients with oropharyngeal primary tumors and PD-L1 expression of at least 1 in 62.5% of the group. Objective responses were assessed every six to nine weeks, and all nine responses were partial responses; no complete responses were recorded. Five patients, or 31.3%, had stable disease, two had progression at the best assessment, and the resulting disease control rate was 87.5%, with a 95% confidence interval of 61.7% to 98.4%.

The objective response rate was 56.3%, with a 95% confidence interval of 29.9% to 80.2%. The one-year progression-free survival estimate was 50.0%, with a 95% confidence interval of 30.6% to 81.6%, while one-year overall survival was 75.0%, with a 95% confidence interval of 56.5% to 99.5%. Median progression-free survival was 9.8 months, with a 95% confidence interval of 2.8 months to not reached, and median overall survival was 17.7 months, with a 95% confidence interval of 12.3 months to not reached.

Eight patients were alive at the end of follow-up, and four of the nine patients with partial responses had ongoing responses at the data cutoff on June 3, 2026. Exploratory biomarker analyses did not reveal a clear response pattern based on PD-L1 expression. Objective responses occurred in three of six patients with a combined positive score of at least 20, two of four with scores from 1 to 19 and three of five with scores below 1, corresponding to response rates of 50.0%, 50.0% and 60.0%, respectively.

Response was observed in two of three p16-positive patients and four of nine p16-negative patients. The small subgroup counts prevent reliable inference about treatment selection or biological determinants of response. The investigators also described a patient whose p16-positive oropharyngeal carcinoma recurred about 16 months after chemoradiotherapy and who then received four cycles of cadonilimab with chemotherapy.

Follow-up imaging showed substantial tumor shrinkage and a partial response, and the regression lasted 15.2 months. This individual observation documented the response seen in that patient, but the study as a whole was not designed to establish effectiveness in an individual case. Safety findings were based on all 16 participants, and every patient experienced at least one treatment-related adverse event.

Four patients, or 25.0%, had grade 3 or higher treatment-related events. These were primarily blood-cell abnormalities: leukopenia occurred in four patients, neutropenia in three, thrombocytopenia in two and anemia in one, with some patients experiencing several events simultaneously. Hypothyroidism was the only immune-related adverse event reported, affecting seven patients, or 43.8%, but all cases were grade 1 or 2.

Patients with grade 2 hypothyroidism were asymptomatic or mildly symptomatic and were managed with oral levothyroxine without interrupting treatment. The investigators reported no grade 3 or higher immune-related adverse events, treatment-related deaths, immune-related cardiac toxicity, colitis, hepatitis, pneumonitis or dermatitis. They cautioned that the absence of some toxicities may reflect the limited sample size and follow-up rather than establish that they cannot occur.

Cadonilimab, also known as AK104, is a tetravalent bispecific antibody designed to block PD-1 and CTLA-4 simultaneously. Its structure eliminates Fc-gamma receptor binding, which the authors say reduces Fc-mediated effector functions and may improve the therapeutic index. The proposed biological rationale is that PD-1 blockade can restore the function of exhausted tumor-reactive T cells already present in the tumor microenvironment, while CTLA-4 blockade can support T-cell priming and expansion by reducing regulatory T-cell-mediated suppression.

Chemotherapy may also contribute through immunogenic tumor-cell death, release of damage-associated molecular patterns and tumor antigens, and changes in the tumor immune environment. These mechanisms provide context for the observed activity, but the single-arm trial cannot determine whether benefit came from cadonilimab, chemotherapy, their combination or an interaction between them. The response rate appears encouraging when placed beside results from other immunotherapy-based studies in recurrent or metastatic head and neck cancer, but cross-trial comparisons are vulnerable to differences in patient selection, trial design, baseline characteristics and standards of care.

The investigators cited a 36.0% response rate for pembrolizumab plus chemotherapy in KEYNOTE-048 and 24.2% for nivolumab plus ipilimumab in CheckMate 651. These comparisons do not establish superiority. The present cohort had several features associated with better outcomes, including ECOG performance status 0 in 75.0% of patients, p16 positivity in half of those with oropharyngeal primary tumors and PD-L1 combined positive scores of at least 1 in 62.5% of the cohort.

The study was also single-center, lacked an anti-PD-1 comparator, did not formally assess health-related quality of life and examined only p16 and PD-L1 as biomarkers. With 16 participants and early termination, the study offers preliminary evidence of activity and manageable observed toxicity, not confirmation of clinical benefit. The authors conclude that adequately powered randomized trials with biomarker stratification are needed to determine whether dual PD-1/CTLA-4 blockade adds benefit to standard PD-1-based regimens.

Subject of Research: Preliminary antitumor activity and safety of first-line cadonilimab plus PF chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma

Article Title: PF chemotherapy combined with a PD-1/CTLA-4 bispecific antibody as first-line treatment in patients with recurrent/metastatic head and neck squamous cell carcinoma: a prospective, single-arm, phase II clinical study

Article References: Liao, W., Li, Q., Deng, Y., Zhang, J., Zhao, Y., & Zhang, S. (2026). PF chemotherapy combined with a PD-1/CTLA-4 bispecific antibody as first-line treatment in patients with recurrent/metastatic head and neck squamous cell carcinoma: a prospective, single-arm, phase II clinical study. Frontiers in Oncology, 16, Article 1961360. https://doi.org/10.3389/fonc.2026.1961360

Image Credits: AI Generated

DOI: 10.3389/fonc.2026.1961360

Keywords: cadonilimab, head and neck cancer, PD-1, CTLA-4, chemoimmunotherapy, phase II trial, recurrent cancer, metastatic cancer, bispecific antibody, platinum chemotherapy, chemotherapy, combined

The research team, led by Meiting Cao and colleagues in the Department of Gynecology and Oncology, divided their cohort into two matched groups of twenty-five patients each. The control group received TC chemotherapy, a widely used backbone of paclitaxel plus carboplatin, together with bevacizumab, a monoclonal antibody that blocks vascular endothelial growth factor and starves tumors of their blood supply. The study group received the same doublet plus tislelizumab, an antibody engineered to bind the programmed death-1 receptor on T cells and release the molecular brake that tumors use to evade immune attack. Follow-up continued until May 2024, allowing the investigators to capture both short-term response and longer-term survival endpoints.

The biological rationale for the triple combination rests on the interplay between tumor vasculature and immune surveillance. Bevacizumab does more than inhibit angiogenesis; by normalizing the disordered tumor vasculature, it can improve oxygen delivery and reduce hypoxia, conditions that otherwise suppress T-cell infiltration and function. Tislelizumab, meanwhile, blocks the PD-1 checkpoint that cervical cancer cells exploit, since human papillomavirus-driven tumors often express the ligands that engage this receptor. Pairing checkpoint blockade with chemotherapy and VEGF inhibition is therefore designed to attack the tumor from three directions simultaneously: direct cytotoxicity, vascular deprivation, and immune reactivation.

The clinical results reported in the study favor the triple-therapy arm on nearly every endpoint measured. Patients receiving tislelizumab achieved significantly better overall clinical efficacy than the control group, with higher complete response rates and longer tumor-free survival intervals, differences that reached statistical significance at the conventional threshold of P less than 0.05. In absolute survival terms, the median overall survival in the study group was 15.8 months compared with 13.2 months in the control group, a difference the authors report as statistically significant with a log-rank chi-square value of 4.92 and a P value of 0.027. Median progression-free survival followed the same pattern, at 13.5 months versus 11.0 months, with a log-rank chi-square of 5.14 and a P value of 0.023.

The survival curves diverged further as time passed. One-year overall survival reached 76.0 percent in the tislelizumab group against 60.0 percent in the control group, and by the two-year mark the gap had widened to 32.0 percent versus 16.0 percent, meaning patients on the triple regimen were twice as likely to be alive at two years. For a disease in which recurrence historically carries a median survival measured in months rather than years, a doubling of the two-year survival proportion represents a clinically meaningful shift, even within a modest sample size. The authors conclude that adding tislelizumab to the chemo-anti-angiogenic backbone significantly improves treatment efficacy and survival while maintaining an acceptable safety profile.

One of the most intriguing aspects of the study is its immunological data. The researchers tracked peripheral blood T-cell subsets, including CD3-positive, CD4-positive, and CD8-positive populations, before and after treatment. After therapy, the study group showed higher circulating CD3-positive and CD4-positive levels and lower CD8-positive levels than the control group, differences that were statistically significant. This shift in T-cell subset distribution suggests that the triple regimen did not merely shrink tumors through cytotoxicity but also measurably altered the systemic immune landscape, potentially reflecting reconstitution of helper T-cell compartments and a rebalancing of the immune response away from exhausted or suppressive states.

Safety findings add an unexpected nuance. Counterintuitively, the incidence of severe adverse reactions, including myelosuppression and gastrointestinal toxicity, was lower in the tislelizumab group during the early phase of treatment. The authors do not provide a definitive mechanistic explanation for this observation, but it is consistent with the possibility that better tumor control and immune modulation may reduce the inflammatory and catabolic burden of progressive disease, or simply that the small sample size influenced the distribution of toxicities. Either way, the safety signal is important because adding a third drug to an already intensive regimen raises obvious concerns about cumulative toxicity, and the study suggests those concerns may be manageable in this population.

The study’s design warrants careful interpretation. As a retrospective analysis of fifty patients at a single institution, it cannot establish causation with the confidence of a randomized controlled trial. Patients were not randomly assigned, and unmeasured differences between the groups, such as performance status, prior treatment history, or disease burden, could have influenced outcomes. The authors note that the study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Shanxi Province Cancer Hospital, with informed consent obtained from all participants, and they declare no competing interests and no external funding. These transparency measures strengthen the report, but the retrospective nature and modest cohort size mean the findings should be viewed as hypothesis-generating rather than definitive practice-changing evidence.

Even so, the results align with a broader trajectory in cervical cancer therapeutics. Checkpoint inhibitors have already demonstrated benefit in advanced cervical cancer in earlier clinical research, and anti-angiogenic therapy with bevacizumab has long been part of the recurrent disease armamentarium. What this study contributes is a direct comparison, within a single cohort, of the standard chemo-anti-angiogenic doublet against the same doublet augmented with PD-1 blockade, along with parallel immune monitoring that hints at how the combination works. The convergence of improved response rates, favorable T-cell subset shifts, and extended survival endpoints paints a coherent picture of a regimen that attacks the tumor and reengages the immune system at the same time.

The road ahead will require prospective validation. Larger, randomized trials will need to confirm the survival advantage, define which patients benefit most, and clarify the long-term safety of the triple combination, particularly immune-related adverse events that may emerge beyond the early treatment window. The authors followed their cohort only until May 2024, and longer observation will be needed to understand durability of response. Nevertheless, for patients facing recurrent cervical cancer, a disease with few good options, the message from this study is cautiously hopeful: a regimen that combines paclitaxel and carboplatin with bevacizumab and tislelizumab delivered longer progression-free and overall survival in this cohort, doubled the two-year survival rate, and did so with an acceptable toxicity profile, offering a promising strategy for managing one of oncology’s most stubborn recurrences.

Subject of Research: Triple-combination therapy with TC chemotherapy, bevacizumab, and tislelizumab for recurrent cervical cancer

Article Title: Effect of TC chemotherapy + Beva + Tislelizumab in patients with recurrent cervical cancer and its influence on survival

Article References: Cao, M., Geng, H., Yan, L., & Zhao, H. (2026). Effect of TC chemotherapy + Beva + Tislelizumab in patients with recurrent cervical cancer and its influence on survival. BMC Cancer. https://doi.org/10.1186/s12885-026-16935-x

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16935-x

Keywords: cervical cancer, tislelizumab, bevacizumab, PD-1 inhibitor, immunotherapy, TC chemotherapy, paclitaxel, carboplatin, recurrent cancer, overall survival, progression-free survival, T-cell subsets