tbuckley/cabot-search huggingface dataset:
Racial disparity in receipt of immunotherapy treatment among elderly patients with head and neck cancer.
Authors: Nosayaba Osazuwa-Peters, Dina K Abouelella, Arun Bhardwaj, Amila Meera Patel, Adnan S Hussaini, Krishnamoorthy Seetharaman, Justin Michael Barnes, Neelima Panth, Eric Adjei Boakye, Tammara L Watts
Journal: Journal of Clinical Oncology (2022)

6049 Background: The United States Food and Drug Administration in 2016 approved immune checkpoint inhibitors (immunotherapy) as a treatment option for head and neck squamous cell carcinoma. However, it is unclear if there are clinical or sociodemographic differences among patients receiving immunotherapy as part of their care. We aimed at characterizing the clinical and non-clinical factors associated with receipt of immunotherapy among elderly patients with head and neck cancer. Methods: We utilized data from Navigating Cancer , which included information on systemic therapy for elderly patients (≥ 65 years), diagnosed with head and neck cancer in a community oncology setting between 2017 and 2021. We estimated clinical (tumor stage [grouped as early, or stage I and II vs. advanced stage, or stage III and IV] and anatomic subsite [oropharyngeal vs. non-oropharyngeal]) and non-clinical (age, smoking history, race, sex, and marital status) factors associated with immunotherapy use based on multivariable logistic regression analysis. Results: There were 4,619 patients in our study cohort, 74.3% male and 87.1% white. Among these patients, 11.1% had received immunotherapy. We found an association between race and receipt of immunotherapy. After adjusting for covariates, white patients with head and neck cancer had 74% increased odds of receiving immunotherapy as part of their treatment (aOR: 1.74; 95% CI 1.25, 2.42), compared to non-whites. There were no statistically significant differences in the odds of immunotherapy use based on age, sex, or smoking history. Patients with non-oropharyngeal disease were significantly more likely to receive immunotherapy than those with oropharyngeal cancer (aOR: 1.26; 95% CI 1.01, 1.56), as were those with advanced stage disease (aOR: 2.72; 95% CI 1.90, 3.91) compared with those early-stage. Conclusions: We identified clinical and non-clinical factors associated with receipt of immunotherapy in this cohort of elderly patients with head and neck cancer, and white patients were significantly more likely to receive immunotherapy as part of their care. Equitable access to immunotherapy and other treatment options will reduce cancer-related health disparities and improve survival of patients with head and neck cancer.
Neoadjuvant toripalimab combined with gemcitabine and cisplatin in resectable locally advanced head and neck squamous cell carcinoma (NeoTGP01): An open-label, single-arm, phase Ib clinical trial.
Authors: Zhigang Liu, Xiaotao Huang, Jun Liang, Guihua Zhong, Ye Liu, Lizhong Liang, Haiyu Hong, Weineng Feng, Shuang Yang, Yaqin Zhang, Yingpeng Peng, Qiandan Liu, Yuling Zhou, Zhaoyuan Zhang
Journal: Journal of Clinical Oncology (2022)

6023 Background: The positive outcome of first-line programmed death receptor-1 (PD-1) inhibitors has been revealed in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Researches about neoadjuvant immunotherapy for resectable locally advanced HNSCC have been proceeding continuously, however the optimal regimen was inconclusive. Here, we combined a powerful chemotherapy regime, gemcitabine plus cisplatin (GP), and a PD-1 inhibitor to treat the potentially resectable locally advanced HNSCC followed by operation for exploring the safety and efficacy of the combination regime in this phase I trial. Methods: This was an open-label, single-arm, phase Ib clinical trial. Untreated patients, aged 18-70, with histologically confirmed localized advanced HNSCC (stage III-IVB), were enrolled. The eligible patients are scheduled to administered PD-1 inhibitor (Toripalimab) 240 mg on day 1, gemcitabine 1000 mg/m 2 on days 1 and 8, and cisplatin 80 mg/m 2 on day 1 every 21 days for two cycles. Radical resection was performed in 4-6 weeks after the first day of the second cycle. The primary endpoints were safety and no surgical-delay rate. Safety evaluation was performed in total participants in 90 days from the first day of treatment (or 30 days after surgery). The second endpoints consisted pathological complete response (pCR) rate, major pathological response (MPR) rate, objective response rate (ORR) and R0 resection rate. Results: By December 10, 2021, twenty-three patients were enrolled. Up to now, 18 out of 23 patients successfully finished the operation on schedule. Grade 3/4 adverse events (AEs) occurred in totally 3 patients (13.0%), 2 (8.7%) case of neutropenia, and one each of fatigue (4.3%), hyperglycemia (4.3%), vomiting (4.3%) and diarrhea (4.3%). The most shared adverse events of grade 1/2 were anorexia (30.4%), fatigue (21.7%), vomitting (17.4%) and hyperglycemia (17.4%). The median interval between second administration and surgery was 33 days. For the 20 patients with available radiological examination at pre- and post-neoadjuvant therapy, the assessment per RESCIST criteria was as follow: 1 (5.0%) CR, 7 (35.0%) PR, 12 (60.0%) SD. R0 resection rate reached 100% in a total of 18 patients with complete surgical resection. Three patients achieved pCR at primary site (viable tumor = 0), 5 achieved MPR (0 &lt; viable tumor≤10%) and 2 among 5 were near-pCR (viable tumor = 1%), and the other 11 patient did not reach MPR. Conclusions: Triweekly neoadjuvant Toripalimab plus GP was generally tolerated by the locally advanced HNSCC and contributed to a major pathological response in 44.4% patients at present. Research Sponsor: Shanghai Junshi Biosciences Co., Ltd. Clinical trial information: NCT04947241.
Phase I results of gunagratinib (ICP-192), a highly selective irreversible FGFR 1-4 inhibitor in patients with head and neck cancer harboring FGF/FGFR gene aberrations.
Authors: Ye Guo, Qun Li, Wenbo Tang, Fengjuan Lin, Junli Xue, Liqiong Xue, Xiaoxiao Ge, Wei Zhao, Wei Zhou, Renbin Zhao, Bin Zhang, Jin Li
Journal: Journal of Clinical Oncology (2022)

6039 Background: The fibroblast growth factor (FGF) and FGF receptor (FGFR) signaling pathway has been evaluated as critical driver of carcinogenesis in multiple cancer types. However, primary results of several FGFR inhibitors showed no or limited response in head and neck cancer (HNC) with FGF/FGFR gene aberrations. Here, we evaluated the efficacy and safety of a novel irreversible pan-FGFR inhibitor gunagratinib in HNC in a first-in-human, phase I/IIa, dose escalation and dose expansion study (ICP-CL-00301 NCT03758664). Methods: In the dose-escalation stage of ICP-CL-00301 study, patients with advanced solid tumors (including HNC) with or without FGF/FGFR gene alterations were treated with escalating doses (range: 2mg-26mg) of gunagratinib once daily in 21-day cycles until disease progression or unacceptable toxicity. Results: 12 HNC patients with or without FGF/FGFR aberrations, including FGF amplification and FGFR mutation, were treated with escalating doses (range: 14mg-22mg) of gunagratinib. Among them, 9 patients harbored FGF/FGFR gene alterations with at least one tumor assessment. The median age of the 12 treated HNC patients was 56 (range: 44 to 75 years) with 75% male and ECOG performance status 1. Among the 9 HNC patients with FGF/FGFR gene aberrations who have completed at least one tumor assessment, 3 patients had partial response (PR), the overall response rate (ORR) was 33.3% (3 of 9 patients). The disease control rate (DCR) was 66.7% (6 of 9 patients). Total of 62 patients with solid tumor were enrolled in ICP-CL-00301 study. The most common treatment-related adverse events (TRAEs) (≥15%) included hyperphosphatemia, diarrhea, increased ALT or AST, increased alkaline phosphatase, hypercalcemia, increased serum creatinine, dry mouth, hypertriglyceridemia, anemia and hyperuricemia. In ICP-CL-00301 study, 3 serious TRAEs were reported, and no serious TRAE were reported in HNC patients. Conclusions: This study demonstrated the anti-tumor activity of gunagratinib in HNC patients carrying FGF/FGFR gene aberrations with an ORR of 33.3%. Gunagratinib is safe and well-tolerated in patients with advanced solid tumors including HNC. Clinical trial information: NCT03758664. Tumor histological type and gene alteration type. Histological Type N=12 [1] squamous cell cancer 8 Ameloblastic carcinoma 2 Nasopharyngeal carcinoma 3 Gene alterations Type N=10 [2] FGF 7 FGFR 3 [1] One patient was a nasopharyngeal carcinoma patient with tongue squamous cell cancer. [2] One patient had no imaging tumor evaluation.
Predicting emergency department use and unplanned hospitalization in patients with head and neck cancer: Development and validation of a machine learning algorithm.
Authors: Christopher W Noel, Rinku Sutradhar, Lesley Gotlib Conn, David Forner, Wing Chan, Rui Fu, Julie Hallet, Natalie Coburn, Antoine Eskander
Journal: Journal of Clinical Oncology (2022)

6021 Background: We recently demonstrated that patient reported symptom burden is strongly associated with emergency department use and unplanned hospitalization (ED/Hosp) in head and neck cancer (Noel et. al 2021 J. Clin Oncol - DOI: 10.1200/JCO.20.01845). We hypothesized that symptom scores could be used to build a tool that would accurately risk stratify patients. Methods: This was a population-based study of patients diagnosed with head and neck cancer between 2007 and 2018. All outpatient clinical encounters were identified. Edmonton Symptom Assessment Scores (ESAS) and clinical and demographic factors were abstracted. Training and test cohorts were randomly generated in a 4:1 ratio. Various machine learning algorithms were explored including: (1) logistic regression, (2) random forest, (3) gradient boosting machines (4) k-nearest neighbors and an (5) artificial neural network. Our main outcome was any 14-day ED/Hosp event following symptom assessment. The performance of each risk model was assessed on the test cohort using the area under the receiver operator characteristic (AUROC) curve and calibration plots. Shapley values were used to identify the variables with greatest contribution to the model. Results: The training cohort consisted of 9,409 patients undergoing 59,089 symptom assessments (80%). The remaining 2,352 patients and 14,193 symptom assessments were set aside as the test cohort (20%). Several models had high predictive accuracy, particularly the gradient boosting machine algorithm (validation AUROC 0.80 [95%CI 0.78-0.81]). A Youden-based cut-off corresponded to a validation sensitivity of 0.77 and specificity of 0.66. A second model built only with symptom severity data had an AUROC of 0.72 [95%CI 0.70-0.74]. Conclusions: Machine learning approaches can be used to predict ED/Hosp in head and neck cancer patients. This tool can risk stratify patients and may help direct targeted intervention.
Nimotuzumab plus chemoradiotherapy versus placebo plus chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma (NPC): A prospective, randomized-controlled, double-blinded, multicenter phase III clinical trial.
Authors: Yan Sun, Chaosu Hu, Qin Lin, Li Gao, Jianhua Wang, Xiaodong Zhu, Junfang Hao, Jin Yi Lang, Peiguo Wang, Ming Ye, Xia Li, Benhua Xu, Rong Wu, Chunmei Bai, Qingshan You, Xiaozhong Chen, Jun Wang, Desheng Hu, Gang Wu, Jian-ji Pan
Journal: Journal of Clinical Oncology (2022)

6001 Background: Epidermal growth factor receptor (EGFR) is highly expressed in most NPC, and it is also an essential factor of prognosis for NPC. nimotuzumab is a humanized anti-EGFR monoclonal antibody. Retrospective clinical studies showed that nimotuzumab combined with chemo-radiotherapy had better survival benefits in locally advanced NPC. The present study is a confirmatory study that aims to assess the clinical efficacy of long-term survival and safety of nimotuzumab combined with chemo-radiotherapy in locally advanced NPC patients. Methods: Patients with locally advanced NPC were randomized (3:1) to receive nimotuzumab (200 mg, weekly, 7-8 weeks) plus chemo-radiotherapy (Arm A) versus chemo-radiotherapy (intensity-modulated radiation therapy or conventional radiotherapy, cisplatin100mg/m 2 /d, 21days/cycle, three cycles) plus placebo (Arm B) as front-line therapy. The primary endpoint was a 5-year OS rate, and the secondary endpoints included disease-free survival and safety. Results: 482 patients in 24 study sites were enrolled (361 in Arm A vs. 121 in Arm B). Both groups were well balanced regarding age, gender, race and ethnicity. The 5-year OS rate was 76.9% in Arm A compared to 64.3% in Arm B (log-rank=4.125, p=0.042). The median DFS was 50.6 months and 42.6 months in Arm A and B, respectively. The 5-year DFS rate was 40.0% in Arm A compared to 14.4% in Arm B (log-rank=1.701, p=0.192). The combination of nimotuzumab plus chemo-radiotherapy was well tolerated. The incidence of adverse drug reactions (ADRs) in Arm A was similar to Arm B (35.7% vs. 42.1%, p=0.207), and the grade 3-5 ADRs as well (17.7% vs.15.7%, p=0.609). Conclusions: Nimotuzumab plus chemo-radiotherapy increase 5-year OS of NPC patients with good safety profile. Clinical trial information: 01074021.
Penpulimab plus anlotinib in patients with recurrent or metastatic head and neck squamous cell carcinoma after the failure of first-line platinum-based chemotherapy: A single-arm, multicenter, phase 2 study.
Authors: Changgong Zhang, Liying Gao, Youxin Tian, Chunmei Bai, Jianhua Chen, Jun Wang, Xingya Li, Yan Sun, Haichuan Su, Zhigang Liu, Yuankai Shi
Journal: Journal of Clinical Oncology (2022)

6027 Background: Penpulimab is a novel human immunoglobulin G1 (IgG1) anti-programmed cell death-1 (PD-1) antibody. The effect of antibody-dependent cell-mediated cytotoxicity and antibody-dependent cellular phagocytosis was eliminated completely by the modification of crystallizable fragment to avoid the FcγR binding. ALTN-AK105-II-01 (NCT04203719) is a single-arm, multi-cohort, multicenter phase 2 study to explore the efficacy and safety of penpulimab plus anlotinib, a multikinase inhibitor inhibiting angiogenesis and tumor cell proliferation simultaneously, in the treatment of various advanced cancers. Here we report the results of the cohort 1 for patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Methods: Eligible pts were diagnosed with histologically confirmed R/M HNSCC and had failed at least one line of platinum-based chemotherapy. Other inclusion criteria included aged 18 years or older, ECOG PS 0-1, and previous anti-angiogenic agents or immune checkpoint inhibitors treatment-naïve. Pts were given penpulimab 200mg intravenously on day 1 and oral anlotinib 12mg once daily from day 1 to day 14 every 3 weeks until disease progression or unacceptable toxicities. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DoR), and safety. Results: From June 1, 2020 to November 22, 2021, 38 pts were enrolled in 8 cencers in China. The sites of primary tumors included oral cavity (15/38, 42.9%), oropharynx (6/38, 15.8%), hypopharynx (4/38 4.5%), larynx (10/38, 26.3%) and others (3/38, 7.9%). As of January 6, 2022 (data cut-off),The study met its primary endpoint that 13 pts achieved partial response (PR) and the ORR (confirmed at least 4 weeks after initial response) was 34.21%. 14 pts obtained stable disease (SD) lasting for at least 4 weeks, given a DCR of 76.32%. After a median follow-up of 6.96 months (95%CI: 4.40, 8.80). PFS events were observed in 17 pts and the median PFS was 8.35 months (95%CI: 5.45, 13.11). The PFS at 6 months was 62.5%. 9 pts died and the median OS was not reached (95% CI: 9.43，NE). For pts with tumor response, the median DoR was not reached (95% CI: 2.37, NE). Treatment-related adverse events (TRAEs) occurred in 89.47% pts, TRAE of grade 3 or above occurred in 39.47% of pts. The most common TRAEs were hypertension (28.95%) and hypothyroidism (28.95%). Conclusions: The combination of penpulimab and anlotinib demonstrated promising efficacy and manageable toxicities in R/M HNSCC pts who failed standard first-line therapy. Further investigation is warranted. Clinical trial information: NCT04203719.
Preliminary safety and efficacy of toripalimab combined with cetuximab in platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC): A phase Ib/II clinical trial.
Authors: Ye Guo, Zhendong Li, Wantao Chen, Meiyu Fang, Zhigang Liu
Journal: Journal of Clinical Oncology (2022)

6022 Background: PD-1 inhibitors and EGFR inhibitors are effective and may provide potential synergy in R/M HNSCC. We launched an open-label, single-arm, multicenter phase Ib/II study of toripalimab (a humanized IgG4K monoclonal antibody specific for PD-1) with cetuximab in platinum-refractory R/M-HNSCC (NCT04856631). We report the results of the phase Ib portion of this study. Methods: Eligible patients with R/M HNSCC progressed upon 1 st -line platinum-containing treatment or developed R/M disease within 6 months of platinum-containing neo-adjuvant/adjuvant or chemo-radiation therapy were enrolled in this study. Exclusion criteria included prior immunotherapy or EGFR inhibitors therapy. Toripalimab was administered at 240mg intravenously Q3W and cetuximab was given as a loading dose of 400mg/m 2 IV followed by 250mg/m 2 QW. Dose-limiting toxicities (DLTs) and de-escalating dose were evaluated by a Safety Monitoring Committee (SMC). If less than 2 DLTs were observed in the first 6 patients, 6 more patients were enrolled to confirm safety. If 2 or more DLTs were observed, the next 6 patients would be enrolled at a lower dose level. The primary endpoint was safety. Secondary endpoints included determination of recommended phase 2 dose (RP2D), ORR, DCR, DOR, and PFS by an independent review committee (IRC) per RECIST v1.1, OS, and PK. Results: A total of 13 patients were enrolled in the phase Ib portion, including 11 (84.6%) male and 2 (15.4%) female patients. The median age was 58 (range 36-74) years. 7 (53.8%) patients had distant metastases and 9 (69.2%) were PD-L1 CPS ≥1. By the data cutoff date of Dec 21, 2021, the median follow-up was 19.3 (1.6-36.3) weeks. No DLT was observed, and the initial dose was chosen as RP2D. 10 (76.9%) patients experienced TRAEs; the most common TRAEs were rash (46.2%) and paronychia (38.5%). 5 (38.5%) patients experienced irAEs, including immune-related skin adverse reactions, hypothyroidism, thyroid function abnormal and duodenitis. No Grade≥3 TRAEs or irAEs occurred. No TRAEs led to discontinuation of study drug. 2 patients reported fatal AEs, both of which were caused by tumor hemorrhage and were judged not related to the study treatment by the SMC. Among 12 patients with at least one post-treatment tumor assessment, 6 confirmed PR (ORR 50%) and 6 SD (DCR 100%) were observed as assessed by the IRC. By the cutoff date, 5 patients have ongoing responses, with 3 over 12 weeks. Conclusions: Toripalimab combined with cetuximab were well tolerated and showed preliminary clinical efficacy in patients with R/M HNSCC. Clinical trial information: NCT04856631.
Reply to E. Topkan et al
Authors: Erin E. Watson, Katrina Hueniken, Junhyung Lee, Sophie H. Huang, Amr El Maghrabi, Wei Xu, Amy C. Moreno, C. Jillian Tsai, Ezra Hahn, Andrew J. McPartlin, Christopher M.K.L. Yao, David P. Goldstein, John R. De Almeida, John N. Waldon, Clifton D. Fuller, Andrew J. Hope, Salvatore L. Ruggiero, Michael Glogauer, Ali Hosni
Journal: Journal of Clinical Oncology (2024)
Liquid Biopsy for Minimal Residual Disease Detection in Head and Neck Squamous Cell Carcinoma (LIONESS): A personalized cell-free tumor DNA analysis for patients with HNSCC.
Authors: Susanne Flach, Karen Howarth, Sophie Hackinger, Christodoulos Pipinikas, Pete Ellis, Kirsten McLay, Giovanni Marsico, Christoph Walz, Christoph A. Reichel, Olivier Gires, Martin Canis, Philipp Baumeister
Journal: Journal of Clinical Oncology (2022)

6017 Background: Despite improvements in multimodal treatment options for patients with head and neck squamous cell carcinoma (HNSCC), survival has only improved modestly over the past decades as patients frequently develop recurrences. Detection of cell-free circulating tumor DNA (ctDNA) post-operatively and during clinical follow-up has the potential to identify patients with molecular residual disease (MRD) or who are at an increased risk of relapse, and who may therefore benefit from personalized treatment strategies. Methods: We conducted LIONESS, a single-center prospective cohort study to investigate ctDNA in patients with HNSCC who received primary surgical treatment with curative intent. 58 patients have been recruited as of January 2022, with disease stage I (15.5%), II (13.8%), III (36.2%) and IV (34.5%). Whole exome sequencing was performed on FFPE tissue. RaDaR, a highly sensitive personalized assay using deep sequencing of tumor-specific variants, was used to analyze serial pre- and post-operative plasma samples for evidence of molecular residual disease and recurrence. In addition, pre-operative saliva samples were collected for detection of tumor DNA in saliva. Results: 236 longitudinal plasma samples from 35 patients have been analyzed so far, using personalized panels designed targeting a median 48 (20-60) somatic variants. Preliminary data shows 94.28% ctDNA detection in baseline samples taken prior to surgery. In post-surgery samples, ctDNA could be detected at levels as low as 0.0005% variant allele fraction (eVAF). Survival analysis showed a significant difference (p-value = 7e-7) in recurrence rates between patients who tested ctDNA+ during follow-up (8/11, 72.7%) and those who were negative for ctDNA (0/24, 0%). In all eight cases with clinical recurrence, ctDNA was detected prior to progression, with lead times ranging from 56 to 265 days. Patients were followed for clinical recurrence with a median follow-up of 9.5 months to date, but longer follow-up is necessary for patients who may be at increased risk of recurrence. Work is ongoing for analysis of the full cohort of plasma and saliva samples, which will be presented at the congress. Conclusions: In this prospective observational study, detection of residual disease using ctDNA was associated with poorer progression-free survival and much earlier detection of disease prior to clinical relapse. The implementation of a highly sensitive ctDNA assay such as RaDaR into clinical practice has the potential to tailor personalized treatment strategies for molecular residual disease and recurrence in patients with HNSCC. In future, ctDNA analysis with subsequent ctDNA-guided treatment may reduce morbidity for HNSCC patients.