scholarly journals Avelumab for platinum-ineligible/refractory recurrent and/or metastatic squamous cell carcinoma of the head and neck: phase Ib results from the JAVELIN Solid Tumor trial

2021 ◽  
Vol 9 (10) ◽  
pp. e002998
Author(s):  
Joël Guigay ◽  
Keun-Wook Lee ◽  
Manish R Patel ◽  
Amaury Daste ◽  
Deborah J Wong ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Solid Tumor ◽  
Objective Response ◽  
Recist 1.1 ◽  
Platinum Based Chemotherapy ◽  
Platinum Refractory ◽  
Grade 3

BackgroundRecurrent and/or metastatic (R/M) disease develops in approximately 65% of patients with squamous cell carcinoma of the head and neck (SCCHN) and is associated with a poor prognosis. Immune checkpoint inhibitors have proven effective in multiple tumor types, including R/M SCCHN. We report the efficacy and safety of avelumab (antiprogrammed death ligand 1 antibody) in an expansion cohort of patients with platinum-refractory/ineligible R/M SCCHN enrolled in the phase I JAVELIN Solid Tumor trial (NCT01772004).MethodsEligible patients with R/M SCCHN were aged ≥18 years and had received ≥1 line of platinum-based chemotherapy with disease progression or recurrence within 6 months of the last dose or were ineligible for platinum-based chemotherapy. All patients received avelumab 10 mg/kg every 2 weeks. Tumor assessments were carried out by a blinded independent review committee (IRC) and investigators according to Response Evaluation Criteria in Solid Tumors V.1.1 (RECIST 1.1). Key endpoints included best overall response, duration of response (DOR) and progression-free survival (PFS) assessed by IRC and investigator per RECIST 1.1, overall survival (OS), and safety.ResultsBetween April 24, 2015, and November 13, 2015, 153 patients were enrolled. Patients had a median of two prior lines of therapy for metastatic or locally advanced disease (range 0–6); 12 patients (7.8%) were not eligible for platinum-based chemotherapy. At data cut-off (December 31, 2017), the confirmed objective response rate was 9.2% (95% CI 5.1% to 14.9%) assessed by IRC and 13.1% (95% CI 8.2% to 19.5%) assessed by investigator. Median DOR was not reached (95% CI 4.2 to not estimable) based on IRC assessment. Median PFS was 1.4 months (95% CI 1.4 to 2.6) assessed by IRC and 1.8 months (95% CI 1.4 to 2.7) assessed by investigator; median OS was 8.0 months (95% CI 6.5 to 10.2). Any-grade treatment-related adverse events (TRAEs) occurred in 83 patients (54.2%) and were grade ≥3 in 10 patients (6.5%). The most common TRAEs were fatigue (n=19, 12.4%), fever (n=14, 9.2%), pruritus (n=12, 7.8%), and chills (n=11, 7.2%), and there were no treatment-related deaths.ConclusionAvelumab showed clinical activity and was associated with a low rate of grade ≥3 TRAEs in heavily pretreated patients with platinum-refractory/ineligible R/M SCCHN.

An open-label single-arm, phase II trial of zalutumumab, a human monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell carcinoma of the head and neck.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6065-6065
Author(s):  
Vassiliki Saloura ◽  
Ezra E.W. Cohen ◽  
Lisa F. Licitra ◽  
Salem Billan ◽  
Jose Dinis ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Skin Rash ◽  
Phase Ii ◽  
Squamous Cell ◽  
Patient Population ◽  
Phase Ii Trial ◽  
Platinum Refractory ◽  
Grade 3

6065 Background: Treatment for patients with platinum-refractory metastatic squamous cell carcinoma of the head and neck (SCCHN) is limited. Cetuximab has been approved in the US in this patient population based on a phase II trial that demonstrated 13% response rate (RR) and 5.9 months median OS. A recently conducted phase III trial of zalutumumab, a human monoclonal IgG1k antibody against EGFR, versus best supportive care showed significant increase in PFS. Here, we present the results of a companion phase II trial in the same patient population. Methods: Patients with platinum-refractory recurrent or metastatic SCCHN received weekly infusions of zalutumumab starting at a loading dose of 8mg/kg. The dose was then reduced to 4mg/kg and individually titrated by increments of 4mg/kg every 2 weeks based on skin rash evaluation up to a maximum of 16mg/kg aiming at a grade 2 skin rash. Primary objective was OS. The analysis was based on the intent-to-treat principle and OS was estimated using the Kaplan-Meier method. Results: Between January 2008 till August 2011 90 patients were enrolled in 57 centers in the United States, Europe and South America. 23% of patients had WHO PS 2 and 74% had distant relapse metastases. Grade 3-4 adverse events (AEs) related to zalutumumab were observed in 19% of the patients and included skin rash (5%), hypomagnesemia (4%) and pneumonitis (1%). Infusion-related reactions occurred in 33% of patients. The frequency of all-cause grade 3-4 AEs was 62% and included infections (14%), gastrointestinal disorders (12%), hypokalemia (6%), dyspnea (9%) and anemia (6%). Two deaths secondary to cardiac arrest in a patient with history of myocardial infarction, and respiratory acidosis in a patient with a pleural effusion and hypomagnesemia were deemed related to zalutumumab. CR was observed in one (1%) patient and PR in four (5%) patients. The median PFS was 8.6 weeks (95% CI [8.0, 10.4]) and the estimated median OS was 5.3 months (95% CI [4.1, 7.1]). Conclusions: Zalutumumab showed reasonable efficacy in platinum-refractory recurrent or metastatic SCCHN patients and dosing titration based on skin rash evaluation was feasible. Clinical trial information: NCT00542308.

scholarly journals Nivolumab in the Treatment of Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (RM-SCCHN): A Report of 16 Cases at a Single Institution

2019 ◽  
Vol 02 (01) ◽  
pp. e7-e10
Author(s):  
Tomoko Yamazaki ◽  
Jiro Aoi ◽  
Kazutaka Kishimoto ◽  
Satoshi Saijo ◽  
Keitaro Fujii ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Disease Control ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Disease Progression ◽  
Squamous Cell ◽  
Drug Discontinuation ◽  
Metastatic Squamous Cell Carcinoma ◽  
Platinum Refractory ◽  
Grade 3

Background Nivolumab, approved in Japan for platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck (RM-SCCHN) in 2017, is of uncertain cost-effectiveness. Patients and Methods We reviewed the data of 16 patients with platinum-refractory RM-SCCHN treated with nivolumab monotherapy, 3 mg/kg every 2 weeks, between April 2017 and February 2018. Results All 16 patients were male. The number of previous treatments was 1, 2, and 3 in 1, 5, and 10 patients, respectively. All patients had been previously treated with regimens that included platinum, and 15 patients had previously received cetuximab. The best response rate was a partial response in two patients. Stable disease occurred in 11 patients and disease progression occurred in 2 patients. The disease control rate was 81.2%. Median follow-up time was approximately 8.7 months, and median progression-free survival (PFS) was 2.1 months. Adverse events (AEs) ≤ Grade 3 included pneumonitis and rash in 38%, pruritus in 31%, fatigue in 25%, and kidney dysfunction and endocrine disorder in 12% each. AEs > Grade 3 included pruritus in 12%, and pneumonitis in 6%. Drug discontinuation was requested by patients' clinicians for disease progression in seven patients and Grade 3 AEs in three. Following nivolumab treatment, seven patients received salvage treatment. Conclusion Nivolumab showed some efficacy in disease control, but PFS was low. The AE rate was acceptable, with no Grade 4 or 5. If patient selection can be fine-tuned, treatment with this agent may become cost-effective.

scholarly journals Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1151
Author(s):  
Shinsuke Suzuki ◽  
Satoshi Toyoma ◽  
Yohei Kawasaki ◽  
Koh Koizumi ◽  
Nobuko Iikawa ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Neck Squamous Cell Carcinoma ◽  
Grade 3

Background and Objectives: In recent years, the effectiveness of chemotherapy after immune checkpoint inhibitor administration has attracted attention in various cancers, including head and neck cancers. However, individual assessments of the administered chemotherapy regimens are insufficient. This study aimed to evaluate the efficacy and safety of chemotherapy after immune checkpoint inhibitor administration in recurrent metastatic head and neck cancer by focusing on a single regimen. Materials and Methods: We retrospectively reviewed clinical and radiological data from the medical records of 18 patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who received systemic chemotherapy with weekly cetuximab and paclitaxel (Cmab + PTX) after progression following immune checkpoint inhibitor (ICI) therapy. The objective response rate (ORR) and disease control rate (DCR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse events (AEs) were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: In all patients, the ORR, DCR, median PFS, and median OS were 44.4%, 72.2%, 3.8 months, and 9.6 months, respectively. Regarding AEs, three patients developed grade 3 neutropenia. Grade 3 anemia, paronychia, asthenia, and peripheral neuropathy were observed in one patient each. There were no treatment-related deaths. Conclusions: Cmab + PTX was shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after ICI therapy. Further research is needed to establish optimal treatment sequences and drug combinations for recurrent R/M HNSCC.

scholarly journals Neoadjuvant docetaxel and cisplatin chemotherapy followed by local irradiation is highly active on locoregionally advanced squamous cell carcinoma of the head and neck

2007 ◽  
Vol 122 (7) ◽  
pp. 722-727 ◽  
Author(s):  
H-J Shin ◽  
J S Chung ◽  
Y J Choi ◽  
B J Lee ◽  
S G Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Remission Rate ◽  
Survival Rates ◽  
Severe Toxicity ◽  
Advanced Squamous Cell Carcinoma ◽  
Highly Active ◽  
Grade 3

AbstractThe purpose of this study was to determine the treatment outcome of neoadjuvant docetaxel and cisplatin chemotherapy followed by local radiotherapy for chemotherapy-naïve patients with locoregionally advanced squamous cell carcinoma of the head and neck. Thirty-seven patients with stage III or IV squamous cell carcinoma of the head and neck who received docetaxel and cisplatin regimen for a maximum of three cycles followed by radiation therapy were enrolled in this study. The overall response rate to the regimen was 91.9 per cent (34 of 37) (the complete remission rate was 48.6 per cent). The median time to treatment failure was 38 months (95 per cent confidence interval, 15–61 months). The four year estimated overall survival rates were 85.1 per cent. The most frequent moderate-to-severe toxicity was grade 3–4 neutropenia. The most common acute non-haematologic toxicities included anorexia, nausea and asthenia. Neoadjuvant docetaxel and cisplatin chemotherapy followed by radiotherapy is a feasible treatment strategy for patients with locoregionally advanced squamous cell carcinoma of the head and neck.

Phase II study of gemcitabine concurrent with radiation in locally advanced squamous cell carcinoma of head and neck: Trial of the Cancer Research Group Pakistan

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15520-15520 ◽  
Author(s):  
A. A. Javed ◽  
A. Shaharyar ◽  
I. H. Shah ◽  
M. A. Shah ◽  
T. N. Ansari ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Total Dose ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Locally Advanced ◽  
Overall Response ◽  
Grade 3

15520 Background: The optimum radiosensitizing dose and schedule of gemcitabine for squamous cell carcinoma of head and neck are not known. The objectives of this study were to evaluate the efficacy and toxicity of weekly gemcitabine as a radiosensitizer concurrent with radical radiotherapy in locally advanced head and neck cancer. Method: Thirty-nine patients with stage III or IV B inoperable carcinoma of head and neck were enrolled. Eligible patients had histopathologically confirmed squamous cell carcinoma with age between 18–70 years. Patients had a KPS >70 with an adequate marrow, hepatic and renal function. No prior chemotherapy or radiotherapy was allowed. Patients with nasopharyngeal, glottic or sub-glottic cancer were excluded. Gemcitabine 150 mg/m2 or a total dose not exceeding 200 mg was given on day 1,8,15,22,29, and 36 during radiation treatment. Gemcitabine was infused in 200 ml of normal saline in 2 hours and radiation was delivered two hours after the completion of gemcitabine infusion. Conventional fractionation was used to deliver a total dose of 66 Gy. CTC version 2.0 of NCI and RTOG/EORTC Late Radiation Morbidity Scoring Scheme were used for evaluation of toxicity and RECIST was used for response evaluation. Results: Only 35 patients were considered evaluable for response. Complete response was seen in 8 (22.9%) (95% CI; 10.4–40.1%), partial response in 25 (71.4%), with an overall response rate of 94.3% (95% CI; 80.8–99.3%). All the thirty-nine patients were evaluable for toxicity. Grade 3 and 4 mucositis was seen in 28 (71.8%) and 2 (5.1%) patients respectively. Grade 3 pharyngeal toxicity was seen in 6 (15.4%). One patient developed pharyngo-cutaneous fistula. Despite vigorous symptomatic and supportive care acute toxicities led to treatment interruption in 16 (41%) of patients. Conclusion: Weekly gemcitabine at a dose of 150mg/m2 concurrent with radiation therapy gives a high overall response rate and a high rate of acute toxicity. No significant financial relationships to disclose.

Exome scale liquid biopsy characterization of putative neoantigens and genomic biomarkers pre- and post anti-PD-1 therapy in squamous cell carcinoma of the head and neck.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6557-6557
Author(s):  
Charles Abbott ◽  
Nikita Bedi ◽  
Simo V Zhang ◽  
Robin Li ◽  
Rachel Pyke ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Solid Tumor ◽  
Liquid Biopsy ◽  
Resistance Mechanisms ◽  
Post Treatment ◽  
Plasma Samples ◽  
Liquid Biopsies

6557 Background: The reduced scope, and number of genes profiled by typical liquid biopsy panels can result in missed biomarkers including neoantigens, which may change with treatment, as well as potentially undetected resistance mechanisms and pathways beyond the scope of targets typically captured by panels. To address these limitations, we used a whole-exome scale liquid biopsy monitoring platform, NeXT Liquid Biopsy, to analyze head and neck squamous cell carcinoma (HNSCC) patients that have received anti-PD1 therapy. Presently, we sought to (1) monitor neoantigen changes in cfDNA as a complement to tumor biopsy-derived neoantigens, (2) compare the impact of tumor escape mechanisms, including HLA-LOH, on neoantigens identified in tissue and cfDNA and (3) to identify novel biological signatures that combine information from both solid tumor and liquid biopsies. Methods: Pre- and post-intervention matched normal, tumor and plasma samples were collected from a cohort of 12 patients with HNSCC. Following baseline sample collection all patients received a single dose of nivolumab, followed by resection approximately one month later when feasible, or a second biopsy where resection was impractical. Solid tumor and matched normal samples were profiled using ImmunoID NeXT, an augmented exome/transcriptome platform and analysis pipeline. Exome-scale somatic variants were identified in cfDNA from plasma samples using the NeXT Liquid Biopsy platform. Data from these two platforms were compared with corresponding clinical findings. Results: Concordant somatic events were detected between plasma and tumor at pre- and post-treatment timepoints. Neoantigens predicted to arise from these somatic events were reduced in solid tumor post-treatment, but increased in cfDNA, when compared to pre-treatment timepoints. HLA LOH was identified in a number of subjects, likely resulting in reduced neoepitope presentation in those cases. Immune cell infiltration increased in the tumor following treatment, with no changes to the CD8+/Treg cell ratio, suggesting consistent immunoregulation. Conclusions: Exome-wide neoantigen burden was reliably predicted from cfDNA, providing additional insight complementing data from solid tumor. Analyzing HLA LOH, and neoantigen burden from both solid and liquid biopsies together over the course of treatment creates a more comprehensive profile of therapeutic response and resistance mechanisms in HNSCC patients missed with typical liquid biopsy panels.

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