Abstract Penpulimab is an anti-programmed cell death-1 (PD-1) IgG1 antibody with no Fc gamma receptor (FcγR) binding activity, and thus theoretically reduced immune-related adverse events (irAEs) while maintaining efficacy. This single-arm, phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma (NPC) who had failed two or more lines of previous systemic chemotherapy. Patients received 200-mg penpulimab intravenously every 2 weeks (4 weeks per cycle) until disease progression or intolerable toxicities. The primary endpoint was objective response rate (ORR) per RECIST (version 1.1), as assessed by an independent radiological review committee. The secondary endpoints included progression-free survival (PFS) and overall survival (OS). One hundred thirty patients were enrolled and 125 were efficacy evaluable. At the data cutoff date (September 28, 2022), 1 patient achieved complete response and 34 patients attained partial response. The ORR was 28.0% (95% CI 20.3–36.7%). The response was durable, with 66.8% still in response at 9 months. Thirty-three patients (26.4%) were still on treatment. The median PFS and OS were 3.6 months (95% CI = 1.9–7.3 months) and 22.8 months (95% CI = 17.1 months to not reached), respectively. Ten (7.6%) patients experienced grade 3 or higher irAEs. Penpulimab has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients, supporting further clinical development as third-line treatment of metastatic NPC.
Nasopharyngeal carcinoma (NPC) has a 10–15% recurrence rate, while no long term or durable treatment options are currently available. Single-cell profiling in recurrent NPC (rNPC) may aid in designing effective anticancer therapies, including immunotherapies. For the first time, we profiled the transcriptomes of ∼60,000 cells from four primary NPC and two rNPC cases to provide deeper insights into the dynamic changes in rNPC within radiation fields. Heterogeneity of both immune cells (T, natural killer, B, and myeloid cells) and tumor cells was characterized. Recurrent samples showed increased infiltration of regulatory T cells in a highly immunosuppressive state and CD8+ T cells in a highly cytotoxic and dysfunctional state. Enrichment of M2-polarized macrophages and LAMP3+ dendritic cells conferred enhanced immune suppression to rNPC. Furthermore, malignant cells showed enhanced immune-related features, such as antigen presentation. Elevated regulatory T cell levels were associated with a worse prognosis, with certain receptor-ligand communication pairs identified in rNPC. Even with relatively limited samples, our study provides important clues to complement the exploitation of rNPC immune environment and will help advance targeted immunotherapy of rNPC.
6033 Background: Nasopharyngeal cancer (NPC) is highly sensitive to chemotherapy and radiotherapy, and concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced NPC (LA-NPC).The effectiveness of platinum-based induction chemotherapy (ICT) with novel agent(s)such as taxane on overall or disease-free survival has been suggested in prospective trials. The purpose of this study is to evaluate the clinical value of observed response to ICT in predicting treatment outcome in patients with LA-NPC. Methods: Between 4/2007 and 8/2014, 687 patients with LA-NPC(i.e., T3, T4, or N+) were treated with platinum-based ICT(100 patients with taxane +/-5FU or gemcitabine [TP/TPF/GP], and 17 with 5FU [PF]) and evaluated for response with MRI were identified. Among the 120 patients who had stable disease (SD) or progression (PD) after ICT (ICT-resistant), 117 were successfully matched for diagnosis/follow-up time, gender, TNM stage, ICT regimen, CRT regimen (none vs. low vs. high dose cisplatin vs. targeted agents), and adjuvant chemotherapy (none vs. TP/TPF/GP vs. PF) to 117of the remaining 567 patients who achieved complete or partial response (CR or PR) after ICT (ICT-sensitive) by propensity score analysis. Results: The median follow-up time was 34 months (range 3-97 months). The overall survival (OS), progression-free survival (PFS), and local/regional/distant-metastatic relaps free survival (LRFS/RRFS/DMFS) rates were significantly better in the ICT-sensitive group (Table). Conclusions: Response to ICT is a significant predictive factor not only for OS, PFS, and DMFS but also for locoregional disease control in patients with LA-NPC. Prospective study is needed to confirm such findings then evaluate whether more aggressive CRT and/or adjuvant chemotherapy regimens may improve the prognosis of the ICT-resistant LA-NPC patients. Treatment outcomes in ICT-sensitive vs ICT-resistant LA-NPC patients. 3-year (%) 5-year (%) P value ICT-resistant ICT-sensitive ICT-resistant ICT-sensitive OS 79.3 94.9 66.1 84.2 0.006 PFS 47.1 86.4 31.1 72.8 <0.001 LRFS 73.0 57.6 97.9 94.4 <0.001 RRFS 80.8 80.8 97.5 97.5 <0.001 DMFS 77.2 66.9 90.8 76.2 0.005
Objectives: We aimed to investigate the long-term survival benefit of PET/CT compared with the routine examination (chest CT, abdominal enhanced CT and emission computed tomography (ECT)) for locally advanced nasopharyngeal carcinoma (NPC) before treatment. Methods: From June 8th 2005 to August 10th 2017, 507 histologically diagnosed NPC patients with the 8th AJCC/UICC staging criteria III-IVA were enrolled in this study. Among them, patients underwent chest CT, abdominal enhanced CT and bone emission CT (control group), or replaced by positron emission tomography-CT (PET-CT group) to check for distant metastases. Results: The numbers of patients in the control and PET-CT group were 344 (67.9%) and 163 (32.1%), respectively. With the median follow-up of 72 months, a total of 127 (25.0%) patients died. The 5-year and 8-year overall survival (OS) rates of the control and PET-CT group were 81.1% and 86.9%, 70.8% and 74.6% (P=0.087), respectively. Patients with T1-3, III stage and TPF showed improved 5-year and 8-year OS rates compared with T4, IVA stage and PF patients (P=0.001, P=0.000 and P=0.009). Patients with initially PET-CT-based staged showed improved 5-year and 8-year distant control (DC) compared with the control group (90.6% vs. 83.3% and 90.6% vs. 81.0%, P=0.013). There was no significant difference in local control (LC) and regional control (RC), between the control and PET-CT group. Conclusions: Patients with initially PET-CT-based staged showed improved long-term DC compared with the control group. Initially PET-CT-based staged is recommended routinely in locoregionally advanced NPC.
To evaluate the predicting factors associated with distant metastasis (DM) for lymphoepithelial carcinoma of salivary gland (LECSG) following postoperative radiotherapy (PORT).We retrospectively collected 160 eligible patients from two cancer institutions. The DM rate was evaluated using competing risk method.The median follow-up time was 65.6 months. Elevated preradiotherapy serum LDH (ratio >0.5) (p = 0.006) and N classification (N2-3) (p = 0.001) were independently associated with DM for the LECSG. After the risk stratification, the high-risk subgroup was defined as the patients presented higher risk score (score >0), whereas 5-year cumulative incidence of DM in the high- and low-risk group was 30.9% and 6.0%, respectively (p < 0.001). Moreover, a significantly worse overall survival (OS) was observed in the high-risk patients compared with the low-risk subgroup (5-year OS: 83.9% vs. 97.8%, p = 0.006).Elevated preradiotherapy serum LDH could serve as a predictive factor for DM in the LECSG following PORT.
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