A phase 2 study of liposomal irinotecan with 5-fluorouracil and leucovorin in squamous cell carcinoma of head and neck or esophagus after prior platinum-based chemotherapy or chemoradiotherapy.

6025 Background: Liposomal irinotecan (nal-IRI) + 5-FU/LV has been approved and used in treating patients with metastatic pancreatic cancer after gemcitabine-based therapy through the NAPOLI-1 study result. This phase 2 trial evaluated the activity of NAPOLI-1 regimen in patients with squamous cell carcinoma (SCC) of head and neck (H&N) or esophagus that progressed on or recur after platinum-based chemotherapy or concurrent chemoradiotherapy. Methods: Patients with histologically confirmed SCC of H&N or esophagus whose disease progressed while on or progressed/recurred within 6 months after platinum-based chemotherapy or chemoradiotherapy, and unsuitable for further surgical or radiation intervention were eligible. Prior anti-EGFR or anti-PD1/anti-PDL1 treatment was allowed. The regimen consisted of nal-IRI 70 mg/m2 (irinotecan free base) followed by LV 400 mg/m2 and 5-FU 2400 mg/m2, every 2 weeks. A Simon’s 2-stage design was used with planned 30 evaluable patients in the first stage and 52 evaluable patients in total. The primary endpoint is objective tumor response. Results: From December 2018 to April 2020, 59 subjects were enrolled, including 16 with esophagus cancer and 43 with H&N cancer. Thirty-seven (63%) patients had metastatic disease at enrollment. The mean of treatment cycles were 5 (range, 1-21). Among the total 59 enrolled subjects, 53 subjects (14 esophagus cancer, 39 H&N cancer) were evaluable for objective tumor response. The disease control rate in esophagus cancer was 50% (7 SD, intent-to-treat (ITT) population 43.8%). For H&N patients, 1 CR, 4 PR, and 23 SD resulted in the response rate 12.8% (11.6% in ITT population) and disease control rate 72% (65% in ITT population). The median progression free survival (N = 59) was 2.5 months (esophagus/H&N: 1.5/2.7 months) and the median overall survival was 5.9 months (esophagus/H&N: 4.2/7.3 months). Seventy-eight percent of patients had ≥grade 3 treatment-related adverse events. The most frequent ≥grade 3 toxicities were decreased lymphocyte count (50.8%), decreased neutrophil count (42.4%), and decreased white blood count (33.9%). Only 3 patients (5%) had grade 3 diarrhea during the treatment period. Conclusions: This study showed the modest efficacy and manageable toxicity profile of nal-IRI+5-FU/LV in platinum-refractory locally advanced or metastatic H&N or esophagus cancer patients. Clinical benefits including complete tumor response were noted in H&N patients. The role of this regimen in selective patients and the efficacy of combination with immunotherapeutic agents warrant further explorations. Clinical trial information: NCT03712397.

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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

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-002998 ◽

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.

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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

International Journal of Practical Otolaryngology ◽

10.1055/s-0039-1685175 ◽

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.

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Phase II Trial of Docetaxel and Cisplatin Combination Chemotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck

Journal of Clinical Oncology ◽

10.1200/jco.2002.20.6.1593 ◽

2002 ◽

Vol 20 (6) ◽

pp. 1593-1599 ◽

Cited By ~ 31

Author(s):

Bonnie S. Glisson ◽

Barbara A. Murphy ◽

Gary Frenette ◽

Fadlo R. Khuri ◽

Arlene A. Forastiere

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Median Time ◽

Squamous Cell ◽

Tumor Response ◽

Survival Rates ◽

Toxic Effects ◽

Standard Regimen ◽

Grade 3

PURPOSE: To assess the antitumor activity and toxicity of docetaxel plus cisplatin chemotherapy in patients with recurrent or incurable squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with recurrent or incurable SCCHN were eligible if they were chemotherapy naive or if they had received one prior regimen as neoadjuvant or concurrent treatment with radiation. Patients who had received chemotherapy for recurrence or prior taxanes were ineligible. Patients received docetaxel 75 mg/m2 and cisplatin 75 mg/m2 on day 1; cycles were repeated every 21 days. RESULTS: Toxic effects and length of survival were assessable in 36 patients and tumor response was assessable in 32, for whom the overall response rate was 40% (13 of 32) (6% complete response and 34% partial response). Median time to response was 5 weeks, and median duration was 4.9 months. In the intent to treat population (n = 36), median time to disease progression was 4 months. Median survival (n = 36) was 9.6 months, and the 12-month survival rate was 27%. Grade 4 neutropenia was observed in 71% of patients. Two patients (6%) experienced serious fever during grade 4 neutropenia (without documented infection) that required intravenous antibiotics, and an additional four patients had grade 3 infection. Other severe (grades 3 and 4) toxic effects were asthenia (25%), nausea (11%), fever (8%), vomiting (8%), severe hypersensitivity reactions (8%), and diarrhea (8%). Severe stomatitis (grade 3) occurred in only one patient. CONCLUSION: Docetaxel plus cisplatin is an effective regimen with an acceptable safety profile for palliation of recurrent SCCHN. Relative to the standard regimen of cisplatin/fluorouracil, this regimen may offer higher tumor response and survival rates with short outpatient administration and a lower incidence of severe mucosal toxicity.

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Palbociclib and cetuximab compared with placebo and cetuximab in platinum-resistant, cetuximab-naïve, human papillomavirus-unrelated recurrent or metastatic head and neck squamous cell carcinoma: A double-blind, randomized, phase 2 trial

Oral Oncology ◽

10.1016/j.oraloncology.2021.105192 ◽

2021 ◽

Vol 115 ◽

pp. 105192

Author(s):

Douglas R. Adkins ◽

Jin-Ching Lin ◽

Assuntina Sacco ◽

Jessica Ley ◽

Peter Oppelt ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Human Papillomavirus ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Phase 2 ◽

Double Blind ◽

Phase 2 Trial ◽

Randomized Phase 2

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

Medicina ◽

10.3390/medicina57111151 ◽

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.

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Debio 1143 and high-dose cisplatin chemoradiotherapy in high-risk locoregionally advanced squamous cell carcinoma of the head and neck: a double-blind, multicentre, randomised, phase 2 study

The Lancet Oncology ◽

10.1016/s1470-2045(20)30327-2 ◽

2020 ◽

Vol 21 (9) ◽

pp. 1173-1187 ◽

Cited By ~ 6

Author(s):

Xu-Shan Sun ◽

Yungan Tao ◽

Christophe Le Tourneau ◽

Yoann Pointreau ◽

Christian Sire ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

High Dose ◽

Advanced Squamous Cell Carcinoma ◽

Phase 2 ◽

Double Blind ◽

Phase 2 Study

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Open-Label, Uncontrolled, Multicenter Phase II Study to Evaluate the Efficacy and Toxicity of Cetuximab As a Single Agent in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Who Failed to Respond to Platinum-Based Therapy

Journal of Clinical Oncology ◽

10.1200/jco.2006.06.7447 ◽

2007 ◽

Vol 25 (16) ◽

pp. 2171-2177 ◽

Cited By ~ 636

Author(s):

Jan B. Vermorken ◽

José Trigo ◽

Ricardo Hitt ◽

Piotr Koralewski ◽

Eduardo Diaz-Rubio ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Combination Therapy ◽

Disease Control ◽

Cell Carcinoma ◽

Head And Neck ◽

Disease Progression ◽

Response Rate ◽

Single Agent ◽

Open Label ◽

Metastatic Squamous Cell Carcinoma

PurposeTo evaluate the efficacy and safety of the epidermal growth factor receptor–directed monoclonal antibody cetuximab administered as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) who experience disease progression on platinum therapy.Patients and MethodsAn open-label multicenter study in which patients with disease progression on two to six cycles of platinum therapy received single-agent cetuximab (initial dose 400 mg/m2followed by subsequent weekly doses of 250 mg/m2) for ≥ 6 weeks (single-agent phase). Patients who experienced disease progression could receive salvage therapy with cetuximab plus platinum (combination-therapy phase). From June 2001 to December 2002, 103 patients were enrolled and treated with cetuximab, 53 of whom subsequently received combination therapy.ResultsIn the single-agent phase, response rate was 13%, disease control rate (complete response/partial response/stable disease) was 46%, and median time to progression (TTP) was 70 days. During the combination-therapy phase, the objective response rate was zero, disease control rate was 26%, and TTP was 50 days. Median overall survival was 178 days. Treatment was well tolerated. The most common cetuximab-related adverse events in the single-agent phase were skin reactions, particularly rash (49% of patients, mainly grade 1 or 2). There was one treatment-related death due to an infusion-related reaction.ConclusionSingle-agent cetuximab was active and generally well tolerated in the treatment of recurrent and/or metastatic SCCHN that progressed on platinum therapy. Response was comparable to that seen with cetuximab plus platinum combination regimens in the same setting.

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