The clinical outcome of pembrolizumab for patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a single center, real world study in China.

Background: The KEYNOTE-048 and KEYNOTE-040 study have demonstrated the efficacy of pembrolizumab in recurrent or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC), we conducted this real-world study to investigate the efficacy of pembrolizumab in patients with R/M HNSCC. Methods: This is a single-center retrospective study conducted in the Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Shanghai, China). Between December 2020 and December 2022, a total of 77 patients with R/M HNSCC were included into analysis. The primary endpoint of the study was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), overall response rate (ORR)and toxicity.Efficacy was assessed according to RECIST version 1.1.SPSS 27.0 and GraphPad Prism 8.0 software were utilized to perform the statistical analysis. Results: By the cut-off date (February 28, 2023), the median OS,PFS and ORR were 15.97 months,8.53 months and 48.9% in patients treated with the pembrolizumab regimen in the first line therapy. Among these patients, 17 patients received pembrolizumab with cetuximab,and 18 received pembrolizumab with chemotherapy.We observed no significant differences between two groups neither in median OS (13.9 vs 19.4 months, P=0.3582) nor PFS (unreached vs 8.233 months, P= 0.2807). In the ≥2nd line therapy (n=30), the median OS, PFS and ORR were 5.7 months, 2.58 months and 20% respectively. Combined positive score (CPS) was eligible from 54 patients. For first line therapy, the median OS and PFS were 14.6 and 8.53 months in patients with CPS ≥1, and median OS and PFS were 14.6 and 12.33 months in patients with CPS ≥20. The immune-related adverse events (irAEs) were occurred in the 31 patients (31/77, 40.26%), and the most common potential irAEs were hypothyroidism (25.97%), and pneumonitis (7.79%). Conclusion: Our real-world results indicated that pembrolizumab regimen is a promising treatment in patients with R/M HNSCC.

A pilot study of camrelizumab with docetaxel and cisplatin for the first line treatment in recurrent/metastatic oral squamous cell carcinoma.

Pembrolizumab with cisplatin and 5-fluorouracil showed survival benefit but relatively high occurrence of treatment-related adverse events (TRAEs) for recurrent/metastatic oral squamous cell carcinoma (R/M OSCC). A more tolerable regime is needed. This trial enrolled 20 R/M OSCC patients with previously untreated and PD-L1 positive. Patients were administered camrelizumab with docetaxel and cisplatin every 3 weeks for six cycles, followed by camrelizumab monotherapy every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was occurrence of grade ≥ 3 TRAEs, secondary endpoints included overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). 45% patients experienced grade ≥ 3 TRAEs, which the most common were anemia (15%), stomatitis (15%), and neutropenia (10%). The most common potential immune-related adverse events were reactive cutaneous capillary endothelial proliferation (RCCEP; 60%), hypothyroidism (35%), and pneumonitis (15%). No treatment-related deaths occurred. The median OS, PFS, and ORR was 14.4 months, 5.35 months, and 40.0% respectively. The study also found RCCEP occurrence, lower FOXP3+ cells, and higher density of intratumor tertiary lymphoid structure were associated with improved efficacy. Our data suggest that camrelizumab with docetaxel/cisplatin as first-line therapy was well tolerable and had potentially favorite efficacy in PD-L1-positive patients with R/M OSCC.

The association between body mass index and efficacy of pembrolizumab as second-line therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma.

BACKGROUND: Recent evidence suggested a potential correlation between BMI and the efficacy of immune checkpoint inhibitors in cancer patients. This study aimed to evaluate the prognostic value of the body mass index (BMI) in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients treat with pembrolizumab. METHODS: The current retrospective cohort study enrolled 49 R/M HNSCC patients underwent at least one cycle of pembrolizumab as second-line treatment from June 2018 to October 2020. Survival analysis of immunotherapy prognosis and risk factor analysis of age, gender, BMI, ECOG-PS, CPS, rT-stage, tumor site, and tube feeding. RESULTS: Among the 49 patients, the BMI at the time of immunotherapy ranged from 14.5 to 32.0 kg/m2 . The Kaplan-Meier analysis showed that the BMI was significantly correlated with overall survival time (OS, p = 0.0007) and progression-free survival time (PFS, p = 0.0012). BMI, gender, prior treatment, serum albumin level, ECOG-PS, CPS and rT-stage were analyzed in multivariate Cox regression model analysis after adjusted for potential confounding clinical variables. Patients with underweight (OS:HR = 6.862, 95% CI:1.566-30.064, p = 0.011; PFS:HR = 5.672, 95% CI:1.364-23.586, p = 0.017);ECOG≥2 (OS:HR = 0.250, 95% CI:0.086-0.731, p = 0.011;PFS:HR = 0.284, 95% CI:0.101-0.805, p = 0.018); CPS <1(OS: HR = 4.34, 95% CI:1.271-15.464, p = 0.019; PFS:HR = 3.859, 95% CI:1.180-12.618, p = 0.025) and rT4-stage(OS:HR = 4.380, 95% CI:1.452-13.209, p = 0.009;PFS: HR = 3.799, 95% CI:1.240-11.638, p = 0.019) suffered higher risk of mortality. CONCLUSIONS: The BMI at the time of clinical diagnosis was showed to be an independent predictive factor for R/M HNSCC patients receiving pembrolizumab. Compared with normal weight patients, underweight patients have worse clinical prognosis.

A novel intronic circular RNA, circGNG7, inhibits head and neck squamous cell carcinoma progression by blocking the phosphorylation of heat shock protein 27 at Ser78 and Ser82.

BACKGROUND: There is increasing evidence that circular RNAs (circRNAs) play a significant role in pathological processes including tumorigenesis. In contrast to exonic circRNAs, which are the most frequently reported circRNAs in cancer so far, the studies of intronic circRNAs have been greatly lagged behind. Here, we aimed to investigate the regulatory role of intronic circRNAs in head and neck squamous cell carcinoma (HNSCC). METHODS: We conducted whole-transcriptome sequencing with four pairs of primary tumor tissues and adjacent normal tissues from HNSCC patients. Then, we characterized circGNG7 expression in HNSCC tissues and cell lines and explored its association with the prognosis of HNSCC patients. We also identified interactions between circGNG7 and functional proteins, which alter downstream signaling that regulate HNSCC progression. RESULTS: In this study, we identified a new intronic circRNA, circGNG7, and validated its functional roles in HNSCC progression. CircGNG7 was predominately localized to the cytoplasm, and its expression was downregulated in both HNSCC tissues andCAL27, CAL33, SCC4, SCC9, HN6, and HN30 cells. Low expression of circGNG7 was significantly correlated with poor prognosis in HNSCC patients. Consistent with this finding, overexpression of circGNG7 strongly inhibited tumor cell proliferation, colony formation, in vitro migration, and in vivo tumor growth. Mechanistically, the expression of circGNG7 in HNSCC cells was regulated by the transcription factor SMAD family member 4 (SMAD4). Importantly, we discovered that circGNG7 could bind to serine residues 78 and 82 of the functional heat shock protein 27 (HSP27), occupying its phosphorylation sites and hindering its phosphorylation, which reduced HSP27-JNK/P38 mitogen-activated protein kinase (MAPK) oncogenic signaling. Downregulation of circGNG7 expression in HNSCC increased HSP27-JNK/P38 MAPK signaling and promoted tumor progression. CONCLUSIONS: Our results revealed that a new intronic circRNA, circGNG7, functions as a strong tumor suppressor and that circGNG7/HSP27-JNK/P38 MAPK signaling is a novel mechanism by which HNSCC progression can be controlled.

The baseline oral microbiota predicts the response of locally advanced oral squamous cell carcinoma patients to induction chemotherapy: A prospective longitudinal study.

PURPOSE: Among oral squamous cell carcinoma (OSCC) patients who receive docetaxel, cisplatin, and 5-fluorouracil (TPF) induction chemotherapy, those with a favorable pathological response tend to obtain satisfactory clinical outcomes, while the total population exhibit no survival benefit. Thus, there is an urgent need to improve the therapeutic effect of TPF by applying personalized treatment according to distinct biomarkers. METHODS AND MATERIALS: In the present study, we collected oral rinse samples from 44 OSCC patients enrolled in our prospective multicenter random phase II trial before TPF induction chemotherapy to conduct 16S rRNA gene sequencing and metagenomic analysis. Patients were administrated with two cycles of TPF induction chemotherapy (75 mg/m2 cisplatin and 75 mg/m2 docetaxel on day 1 and 750 mg/m2 fluorouracil from the first to the fifth day), and then divided into responsive and nonresponsive groups according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RESULTS: In the 16S rRNA gene sequence analysis, Fusobacterium and Mycoplasma were more enriched in the nonresponsive group, while Slackia was more enriched in the responder group at the genus level. In the metagenomic shotgun sequencing analysis, Fusobacterium nucleatum was more enriched in the nonresponsive group. Functional analysis showed that the platinum drug resistance pathway and microRNAs in cancer and RNA degradation pathways were remarkably associated with patient sensitivity to induction chemotherapy. CONCLUSIONS: Our data suggest that the oral microbiome may play an important role in the OSCC patient sensitivity to TPF induction chemotherapy and offer novel potential biomarkers for predicting the response to TPF induction chemotherapy.