Potential of a Utidelone‑Containing Quadruple Regimen for Taxane‑Pretreated Advanced Nasopharyngeal Carcinoma: A Case Report

Technical Summary: Potential of a Utidelone‑Containing Quadruple Regimen for Taxane‑Pretreated Advanced Nasopharyngeal Carcinoma

Problem Statement
Distant metastasis, particularly multiple liver metastases, represents a critical clinical bottleneck in the management of advanced nasopharyngeal carcinoma (NPC). While first-line treatment for recurrent or metastatic NPC (RM-NPC) typically involves gemcitabine plus cisplatin combined with immunotherapy or targeted agents, most patients eventually develop platinum resistance. Furthermore, subsequent lines of therapy are limited in efficacy. A specific challenge arises in patients who have progressed after taxane-based therapy or who exhibit severe toxicity to taxanes (e.g., albumin-bound paclitaxel), leaving few viable options. Standard later-line regimens often yield poor progression-free survival (PFS), particularly in the setting of high tumor burden like multiple liver metastases. Additionally, the overexpression of P-glycoprotein (P-gp) in tumor cells frequently mediates multidrug resistance (MDR) against taxanes, rendering re-challenge with similar microtubule inhibitors ineffective.

Methodology
This study presents a single-case report of a 59-year-old Han Chinese male diagnosed with T3N2M0 non-keratinizing NPC. The patient initially achieved a complete response (CR) following radical intensity-modulated radiotherapy (IMRT) combined with nab-paclitaxel, carboplatin, and nimotuzumab. However, 18 months post-treatment, he developed multiple liver metastases. Due to a history of Grade 3 skin toxicity and persistent neuropathy from the initial taxane-based regimen, the patient was deemed unsuitable for further taxane re-challenge.

Consequently, a salvage quadruple regimen was empirically designed and administered starting July 26, 2023. The regimen consisted of:

1. Utidelone (UTD1): 30 mg/m² intravenously daily on days 1–5. UTD1 is a novel epothilone microtubule inhibitor developed in China, noted for its ability to bypass P-gp-mediated MDR.
2. Carboplatin: 580 mg on day 1 (leveraging a 10-month platinum-free interval to suggest retained sensitivity).
3. Nimotuzumab: 400 mg on day 1 (selected based on EGFR positivity in the tumor).
4. Zimberelimab (PD-1 inhibitor): 240 mg on day 1.

The patient received six cycles of this combination every 21 days, followed by zimberelimab maintenance monotherapy. Tumor response was evaluated using RECIST 1.1 criteria, serum tumor markers (CA125, CYFRA21-1, NSE), and imaging. Adverse events were monitored according to CTCAE standards. Notably, the study did not perform Next-Generation Sequencing (NGS) or PD-L1 expression analysis due to tissue and financial constraints.

Key Results

• Efficacy: Following the six cycles of the quadruple regimen, the patient achieved a Complete Response (CR) in liver metastatic lesions. Tumor markers decreased rapidly, normalizing or approaching normal levels by January 2024.
• Durability: As of the last follow-up on October 20, 2025, the patient remained in CR with a progression-free survival (PFS) exceeding 24 months. Plasma EBV-DNA was undetectable (< 2×10² IU/mL).
• Safety: The treatment was well-tolerated. Adverse events were limited to Grade 1–2 peripheral neuropathy and mild myelosuppression. Crucially, the pre-existing neuropathy did not worsen, and no Grade 3 skin toxicity occurred, contrasting sharply with the patient's initial therapy.
• Patient Perspective: The patient reported that the side effects of the salvage regimen were significantly more manageable than the severe skin toxicity experienced during first-line therapy.

Significance and Claims
The paper posits that a UTD1-based quadruple regimen offers a viable salvage strategy for advanced NPC patients who are taxane-pretreated, taxane-intolerant, or have developed multiple liver metastases. The authors highlight several key points:

• Mechanism of Action: The efficacy is attributed to UTD1's unique ability to bypass P-gp-mediated multidrug resistance, maintaining antitumor activity in cells that have developed resistance to taxanes. The combination likely induces synergistic effects, potentially involving immunogenic cell death (ICD) and PD-L1 upregulation, though the specific contribution of each agent in the quadruple regimen cannot be isolated in this single case.
• Clinical Outcome: The achieved PFS of >24 months is notable when compared to the median PFS of 2–4 months typically observed in conventional later-line therapies for this patient population, and significantly higher than the 4–6 months seen in other PD-1 inhibitor or chemotherapy trials (e.g., KEYNOTE-122).
• Modesty and Limitations: The authors explicitly acknowledge the limitations of a single-case report, noting that findings are not generalizable and that the specific contribution of the four-drug combination cannot be determined. They do not claim this regimen as a new standard of care but rather as a "compelling signal" warranting further investigation. The study serves as preliminary evidence to support the exploration of UTD1-containing combinations in taxane-resistant NPC settings.

In conclusion, this case report provides preliminary clinical evidence that a UTD1-containing quadruple regimen can achieve durable disease control and a complete response in a heavily pre-treated NPC patient with multiple liver metastases, offering a potential therapeutic avenue where options are currently scarce.