Recurrent/metastatic Head And Neck Squamous Cell Carcinoma Research Articles

De novo metastatic head and neck squamous cell carcinoma: Why does locoregional control “always” matter?

De novo metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) constitutes 10% of recurrent/metastatic (RM) cases. Radiotherapy (RT) has a crucial role in the treatment of locally advanced HNSCC, however its application on RM diseases is still limited. The advent of immune checkpoint inhibitors (ICIs) improves the survival of RM HNSCC, however median overall survival is still limited. Integration of locoregional RT with ICIs in de novo metastatic HNSCC represents a promising treatment option. This perspective aims to explore the role of the combination of locoregional and systemic treatment in improving outcomes for synchronous de novo metastatic HNSCC patients and highlights the principal crucial point in decision making.

Pembrolizumab and Cabozantinib in Recurrent Metastatic Head and Neck Squamous Cell Carcinoma (RMHNSCC): 2-year Long Term Survival Update with Biomarker Analysis

Pembrolizumab and Cabozantinib in Recurrent Metastatic Head and Neck Squamous Cell Carcinoma (RMHNSCC): 2-year Long Term Survival Update with Biomarker Analysis

A transcriptomic map of EGFR-induced epithelial-to-mesenchymal transition identifies prognostic and therapeutic targets for head and neck cancer

BackgroundEpidermal growth factor receptor (EGFR) is both a driver oncogene and a therapeutic target in advanced head and neck squamous cell carcinoma (HNSCC). However, response to EGFR treatment is inconsistent and lacks markers for treatment prediction. This study investigated EGFR-induced epithelial-to-mesenchymal transition (EMT) as a central parameter in tumor progression and identified novel prognostic and therapeutic targets, and a candidate predictive marker for EGFR therapy response.MethodsTranscriptomic profiles were analyzed by RNA sequencing (RNA-seq) following EGFR-mediated EMT in responsive human HNSCC cell lines. Exclusive genes were extracted via differentially expressed genes (DEGs) and a risk score was determined through forward feature selection and Cox regression models in HNSCC cohorts. Functional characterization of selected prognostic genes was conducted in 2D and 3D cellular models, and findings were validated by immunohistochemistry in primary HNSCC.ResultsAn EGFR-mediated EMT gene signature composed of n = 171 genes was identified in responsive cell lines and transferred to the TCGA-HNSCC cohort. A 5-gene risk score comprising DDIT4, FADD, ITGB4, NCEH1, and TIMP1 prognosticated overall survival (OS) in TCGA and was confirmed in independent HNSCC cohorts. The EGFR-mediated EMT signature was distinct from EMT hallmark and partial EMT (pEMT) meta-programs with a differing enrichment pattern in single malignant cells. Molecular characterization showed that ITGB4 was upregulated in primary tumors and metastases compared to normal mucosa and correlated with EGFR/MAPK activity in tumor bulk and single malignant cells. Preferential localization of ITGB4 together with its ligand laminin 5 at tumor-stroma interfaces correlated with increased tumor budding in primary HNSCC tissue sections. In vitro, ITGB4 knock-down reduced EGFR-mediated migration and invasion and ITGB4-antagonizing antibody ASC8 impaired 2D and 3D invasion. Furthermore, a logistic regression model defined ITGB4 as a predictive marker of progression-free survival in response to Cetuximab in recurrent metastatic HNSCC patients.ConclusionsEGFR-mediated EMT conveyed through MAPK activation contributes to HNSCC progression upon induction of migration and invasion. A 5-gene risk score based on a novel EGFR-mediated EMT signature prognosticated survival of HNSCC patients and determined ITGB4 as potential therapeutic and predictive target in patients with strong EGFR-mediated EMT.

The impact of patient preference in the treatment algorithm for recurrent/metastatic head and neck squamous cell carcinoma

The advent of immune checkpoint inhibitors for recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC) has revolutionized the standard of care approach in first-line treatment. The heterogeneity of disease presentation and treatment-related toxicities can be associated with suboptimal patient compliance to oncologic care. Hence, prioritizing quality of life and well-being are crucial aspects to be considered in tailoring the best treatment choice. The aim of our work is to present a short report on the topic of the patient’s preference in regard to treatment and its consequences on quality of life in the recurrent/metastatic setting. According to the literature, there’s an unmet need on how to assess patient attitude in respect to the choice of treatment. In view of the availability of different therapeutic strategies in first-line management of RM-HNSCC, increasing emphasis should be put on integrating patient preferences into the medical decision-making.

A phase II trial of pembrolizumab and cabozantinib in patients (pts) with recurrent metastatic head and neck squamous cell carcinoma (RMHNSCC).

6008 Background: Pembrolizumab (pembro) is an immune checkpoint inhibitor (ICI) approved for treating pts with recurrent/metastatic (RM) HNSCC. Cabozantinib (cabo) is a multiple receptor tyrosine kinase inhibitor (TKI) targeting MET and VEGFR2 shown to reduce tumor growth, metastasis, and angiogenesis and has immuno-modulatory properties. Methods: This is a phase II, open label multi-center, single arm trial evaluating the tolerability and clinical benefit of pembro administered at 200 mg every 3 weeks and cabo 40 mg daily for pts with RM HNSCC who have not received prior ICI. It had a lead-in safety cohort allowing reduction of cabo dose to 20mg daily. Eligible pts had RM HNSCC, deemed incurable, with a tumor PD-L1 CPS > 1, RECIST 1.1 measurable disease, a life expectancy of > 3 months, an Eastern Cooperative Group (ECOG) Performance Status (PS) of 0-1. Enrollment was initiated in March of 2019. We estimated that the ORR will improve to 35% with pembro+ cabo (from a historic of 18%) with a significance level of 0.05 and 80% power. Results: A total of 47 pts were screened, 13 screen failures [cavitation on scan (4), inability to swallow pills (2), other exclusions (7)]; 34 pts were enrolled, 32 were dosed and 31 evaluable (at least one follow-up scan). Pts had cancers of the oropharynx (21, 65%), nasopharynx (6, 19%), larynx/hypopharynx (4, 13%) and oral cavity (1,3%). 32 patients received cabo at 40 mg daily; 13 patients (41%) were dose reduced to 20mg daily [mucositis, increased liver function (LFT) tests, diarrhea]; males (n=29, 90%), median age 63 years (range 53-67); presence of distant metastases (34, 100%); prior radiation (29, 90%), chemotherapy (14, 43%); ECOG PS =0 (16, 50%), 1 (16,50%); HPV/p16 positive (17, 53%), negative (5, 16%), not applicable (10, 29%); the most frequent adverse event (AE) (all grades) was fatigue (16,50.0%), grade 3 or 4 treatment-related AE were increased LFTs, hyponatremia (3, 9.3% each). With a median follow up of 12.7 months (mos) (range 6.9- 20.5 mos), a RECIST 1.1 overall response rate ORR= 45.2% (CR=0; PR=14, 45.2%; SD =14, 45.2%; PD=3.0, 10%) with an overall clinical benefit of 90.4% were observed; The 1-yr OS was 67.7% (95% CI, 42.9%-83.6%; median 22.3 mos) and 1-yr PFS was 51.8% (95% CI, 28.8%-70.7%; median 14.6 mos). Conclusions: This phase II trial of pembro + cabo met its primary endpoint of ORR. The regimen is well-tolerated with very encouraging clinical activity in RM HNSCC and warrants further exploration in this disease. The study was supported by a grant from Exelixis to NFS. Clinical trial information: NCT03468218.

Performance status (PS) as a predictor of poor response to immune checkpoint inhibitors (ICI) in recurrent/metastatic head and neck cancer (RMHNSCC) patients.

Anti-PD1 checkpoint inhibitors (ICI) represent an established standard-of-care for patients with recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC). Landmark studies excluded patients with ECOG performance status (PS) ≥2; the benefit of ICI in this population is therefore unknown. We retrospectively reviewed RMHNSCC patients who received 1+ dose of ICI at our institution between 2013 and 2019. Demographic and clinical data were obtained; the latter included objective response (ORR), toxicity, and any unplanned hospitalization (UH). Associations were explored using uni- and multivariate analysis. Overall survival (OS) was estimated using a Cox proportional hazards model; ORR, toxicity, and UH were evaluated with logistic regression. Of the 152 patients, 29 (19%) had an ECOG PS ≥2. Sixty-six (44%) experienced toxicity; 54 (36%) had a UH. A multivariate model for OS containing PS, smoking status, and HPV status demonstrated a strong association between ECOG ≥2 and shorter OS (p< 0.001; HR=3.30, CI=2.01-5.41). An association between OS and former (vs. never) smoking was also seen (p< 0.001; HR=2.17, CI=1.41-3.35); current smoking did not reach statistical significance. On univariate analysis, poor PS was associated with inferior ORR (p= 0.03; OR=0.25, CI=0.06-0.77) and increased UH (p= 0.04; OR=2.43, CI=1.05-5.71). There was no significant association between toxicity and any patient characteristic. We observed inferior OS, ORR, and rates of UH among ICI-treated RMHNSCC patients with ECOG 2/3. Our findings help frame discussion of therapeutic options in this poor-risk population.

Abstract 1112: Feasibility of real-time personalized patient-derived Tumorgraft® models for guiding systemic treatment in recurrent and/or metastatic head and neck cancer patients

Abstract Background: Recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC) is associated with poor quality of life and a poor prognosis with a median overall survival of 7 months. With limited systemic therapy options, there is an urgent need to identify predictive biomarkers for drug response. Patient derived xenografts (PDXs) have been demonstrated to preserve the histological features, heterogeneity, epigenetic and genetic profiles of the original tumor and appear to correlate well with objective tumor response in patients. This study aimed to test the feasibility of personalized PDXs for guiding systemic treatment in RMHNSCC. Methods: Eligible patients were consented and a fresh biopsy/surgical sample was obtained and implanted into mice (5-15 mice/patient) to establish TumorGraft® models. Engrafted tumors were excised and propagated into second generation models for drug testing with up to 4 drugs selected by the treating medical oncologist. Tumor dimensions were measured twice weekly and were reported as one of: progressive disease, stable disease (SD), partial response (PR), or complete response (CR) based on the percentage of tumor regression. Patients alive and suitable for chemotherapy were prescribed the regimen(s) observed to have the greatest response rate in their TumorGraft® models. Patients' responses to therapy were then observed. Results: Nine of 10 eligible patients had samples successfully engrafted with an average time to engraftment of 89.2 days (± SD 41.7 days). Drug testing was not performed on 5 patients as the patient either died or was not suitable for treatment. The remaining 4 patient TumorGraft® models underwent drug testing with the average time from engraftment completion to drug testing completion being 83.8 ± 59.9 days. Two of these patients then received xenograft-guided therapy. In one patient, paclitaxel demonstrated a partial response in the Tumorgraft®, however the patient's tumor did not respond and their clinical status rapidly deteriorated leading to death. In the second patient, cetuximab and paclitaxel demonstrated the best response in the TumorGraft® model. This patient had a sequential partial response to each drug including a 17 month response to cetuximab before progressing and transitioning to nivolumab. The patient remains alive with stable disease 3.5 years after diagnosis of recurrent disease. Conclusions: The main limitation of Tumorgraft® testing for this population is the time delay to obtain Tumorgraft® results. Despite this, Tumorgraft® testing is feasible for a subset of patients and appears to correlate with clinical benefit. Citation Format: Morgan D. Black, Allison Berger, Nicole Pinto, John Yoo, Kevin Fung, Danielle MacNeil, David A. Palma, Joseph S. Mymryk, Sara Kuruvilla, John W. Barrett, Suzanne Richter, Angela Davies, Eric W. Winquist, Anthony C. Nichols. Feasibility of real-time personalized patient-derived Tumorgraft® models for guiding systemic treatment in recurrent and/or metastatic head and neck cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1112.

End-of-life health care utilization (EOLHCU) in patients with recurrent, metastatic head and neck squamous cell carcinoma (RMHNSCC) treated with immune checkpoint inhibitors (IO).

e18516 Background: Demographic and EOLHCU trends are undefined in the growing population of IO-treated RMHNSCC; we sought to study these in a single institution retrospective study. Methods: We identified 228 RMHNSCC pts who received ≥1 IO dose between 01/2013 and 12/2018; of these, 74 were deceased with accessible EOLHCU data such as advanced care plan documentation (ACPD) or evidence of systemic therapy or ER/hospital/ICU admission within 30 days of death (DOD). Demographic, tumor and treatment data were obtained. Overall survival (OS) was estimated using the Kaplan Meier method; multivariable analysis was performed using a Cox proportional hazards model. In an exploratory analysis, EOLHCU was compared to a cohort of 379 deceased thoracic malignancy (TM) pts using a chi-square test. This project was approved by our institutional IRB. Results: Median pt age was 62 (25 – 90). Most were male (56, 75%), white (60, 81%), current/former smokers (46, 62%); 34 (46%) smoked ≥10 pack years. Common primary sites included the oral cavity (28, 37.8%) and oropharynx (24, 32.4%). ECOG PS at IO initiation was 0 in 15 pts (20%,) 1 in 37 (50%), 2 in 20 (27%), 3 in 1 (1%), and unknown in 1 (1%). Of the 42 (57%) treated off-trial, 18 (42%) had an ECOG ≥ 2. 71 (95%) had prior curative intent therapy. 42 (57%) had distant metastases. Compared to TM, IO-treated RMHNSCC pts were more likely to have ACPD (66% vs. 45% p &lt; 0.01), an ED visit (42.3% vs 19.5%, p &lt; 0.01) and/or a hospital admission (42.3% vs 17%, p &lt; 0.01) within 30 DOD. There was no difference in ICU admissions within 30 DOD (9.9% vs. 8.2%, p = 0.81), ICU deaths (7% vs. 4%, p = 0.4), or systemic therapy within 7 (4.2% vs. 2.4%, p = 0.63), 14 (8.5% vs. 6.6%, p = 0.76) or 30 (25% vs 19%, p = 0.31) DOD. Among IO-treated RMHNSCC pts, multivariable analysis revealed inferior OS with worse PS (ECOG 2-3 vs. 0: HR = 7.76, p = 0.00002, 95% CI = 3.07 - 19.64; ECOG 1 vs. 0: HR = 2.97, p = 0.008, CI = 1.33 - 6.62). OS also decreased with smoking status (current/former vs. never: HR 2.18, p = 0.007, CI = 1.24-3.84). No association was observed between ECOG PS, age or smoking status at IO initiation and any EOLHCU metric. Conclusions: At our center, a significant proportion of deceased, IO-treated RMHNSCC pts had an ECOG PS ≥ 2 and an inferior OS compared to ECOG 0/1. Exploratory comparison with a non-RMHNSCC TM cohort suggests high rates of EOLHCU within 30 DOD despite ACPD, representing an opportunity for supportive care augmentation. Whether EOLHCU differs among IO vs non-IO treated RMHNSCC is unknown and merits further study.

1140P - A single-arm, open-label, multicenter, phase IIIb clinical trial with nivolumab in subjects with recurrent or metastatic platinum-refractory squamous cell carcinoma of the head and neck

1140P - A single-arm, open-label, multicenter, phase IIIb clinical trial with nivolumab in subjects with recurrent or metastatic platinum-refractory squamous cell carcinoma of the head and neck

Meta-analysis of the effects of anti-epidermal growth factor receptor on recurrent/metastatic head and neck squamous cell carcinoma.

Background:We performed a meta-analysis to compare the efficacy and safety of anti-epidermal growth factor receptor (EGFR) therapy and non-anti-EGFR therapy in recurrent/metastatic (RM) head and neck squamous cell carcinoma (HNSCC).Methods:The Cochrane library, WanFang Data, PubMed, Medline, VIP, CBM, and EBSCO databases were searched for relevant studies. The objective response rate (ORR, defined as complete response or partial response according to RECTST version 1.1) and grade 3 to 4 adverse effects were used.Results:Ten studies involving 2260 patients were included. Primary meta-analysis showed that anti-EGFR therapy improved the ORR [odds ratio (OR): 1.79, 95% confidence interval 1.44–2.21, P <.00001]. Subgroup analyses revealed that the ORR of patients with RM HNSCC could be improved by monoclonal antibodies (OR: 1.89, 1.46–2.45, P <.00001) and tyrosine kinase inhibitors (OR: 1.57, 1.07–2.31, P = .02). Analysis of grade 3 to 4 adverse effects demonstrated that diarrhea (3.15, [1.90, 5.20]), rash/desquamation (13.66, [6.86, 27.20]), hypomagnesemia (1.83, [1.28, 2.62]), vomiting (1.99, [1.00, 3.95]), anorexia (3.34, [1.45, 7.73]), dehydration (2.22, [1.19, 4.12]), and hypokalemia (1.63, [1.09, 2.42]) were significantly associated with anti-EGFR therapy.Conclusion:Anti-EGFR therapy is recommended for patients with RM HNSCC. Adverse effects, such as diarrhea, anorexia, hypomagnesemia, and hypokalemia, should be carefully monitored during anti-EGFR therapy.

1044O - A phase Ib/II study (SCORES) of durvalumab (D) plus danvatirsen (DAN; AZD9150) or AZD5069 (CX2i) in advanced solid malignancies and recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC): Updated results

1044O - A phase Ib/II study (SCORES) of durvalumab (D) plus danvatirsen (DAN; AZD9150) or AZD5069 (CX2i) in advanced solid malignancies and recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC): Updated results

Multicenter Phase 2 Trial of Cis/Carboplatin, nAb-Paclitaxel, and CeTUXimab (CACTUX) as First-Line Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Standard first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC) is 5-FU, cetuximab and platin (EXTREME). The EXTREME regimen resulted in a median progression-free survival (PFS) of 5.6 months, tumor response rate (RR) 36%, and overall survival (OS) 10.1 months. The risk of grade 4 adverse events (AEs) was 31%. More effective and less toxic regimens are needed. In this multicenter phase 2 trial, we hypothesized that substitution of 5-FU in EXTREME with nab-paclitaxel would increase the median PFS from 5.6 (historical) to 7.6 months (35% increase, power 0.80, P= .05, one-sided test, N= 70 patients). Patients with incurable RM-HNSCC were treated with the CACTUX regimen as first-line therapy: nab-paclitaxel (100 mg/m2/week), cetuximab (400 mg/m2, then 250 mg/m2/week), and carboplatin (AUC 5, Day 1) or cisplatin (75 mg/m2, Day 1) in three-week cycles x 6, then maintenance nab-paclitaxel (Days 1, 8) and cetuximab (weekly) until disease progression. Tumor response assessments (RECIST 1.1) were performed every two cycles. Efficacy endpoints included PFS, RR and OS. AEs were graded using CTCAE v3.0. Thirty-two patients were the subject of this planned interim analysis. Patient/tumor characteristics included a median age of 58 years, HPV-related oropharynx (19 patients), and HPV-unrelated HNSCC (13 patients). The median PFS was 6.3 months (95% CI: 4-9.4), RR of 50% and median OS was 18.4 months. Current status: alive without progression (8 patients), alive with progression (7), and expired (17). Grade 4 AEs occurred in 6 patients (19%). Only seven patients (22%) received PD-1 inhibitor immunotherapy (IT) after progression: median PFS with IT was 2.2 months (range 0.3-9.5). The CACTUX regimen resulted in a median PFS of 6.3 months and RR of 50%. The median OS of 18.4 months is the highest ever reported with first-line therapy for patients with incurable RM-HNSCC.

Clinical benefit of nanoparticle albumin-bound-paclitaxel in recurrent/metastatic head and neck squamous cell carcinoma resistant to cremophor-based paclitaxel or docetaxel.

The clinical benefit of nab-paclitaxel monotherapy for recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC) that progressed on other taxanes (cremophor-based paclitaxel or docetaxel) is unknown. A retrospective analysis of patients treated at a single institution with nab-paclitaxel for taxane-resistant RM-HNSCC. The exploratory hypothesis was that nab-paclitaxel would result in clinical benefit (tumor response) in patients with taxane-resistant RM-HNSCC. Twelve patients who were treated with nab-paclitaxel monotherapy for taxane-resistant RM-HNSCC and met all eligibility criteria were identified. The majority of patients (n=9; 75%) received three or more lines of therapy for RM-HNSCC. All patients had platin-resistant, and ten patients (83%) had cetuximab-resistant disease. Patients had RM-HNSCC that progressed on cremophor-based paclitaxel (8), docetaxel (1), or both (3). With prior taxane, the best tumor response was partial (PR) in 4 patients (33%), stable (SD) in 3 (25%), and progression in 5 (42%). The median time-to-progression (TTP) with prior taxane was 1.7 (range 0.7-9.0) months. The median interval from last dose of taxane to first dose of nab-paclitaxel was 3 (0.7-31.3) months. With nab-paclitaxel, tumor response occurred in two patients (17%; PR in both) and disease control (PR and SD) occurred in five (42%). Median TTP with nab-paclitaxel was 2.1months (range 0.6-6.2), and median overall survival was 4.9months (range 1.9-13.5). nab-Paclitaxel provided clinical benefit in some patients with taxane-resistant RM-HNSCC. The median TTP with nab-paclitaxel and with prior taxane were similar. This exploratory observation warrants further investigation in prospective studies.

Predictors of outcome with cetuximab and paclitaxel for head and neck squamous cell carcinoma.

Identify predictors of outcome in patients with recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC) treated with weekly cetuximab and paclitaxel (CP). Retrospective analysis. Patients with RMHNSCC treated with CP were identified and patient data was recorded. The Kaplan-Meier method was used to estimate outcomes, and Cox regression analysis was used to examine outcome predictors. Fifty-nine patients initiated CP between January 2007 and June 2014. Median age was 56 (range: 39-80) years. The most common primary sites were the oropharynx in 22 (37%) patients, oral cavity in 19 (32%), and larynx in 11 (19%). Eastern Cooperative Oncology Group performance status (ECOG PS) was 0 in seven (12%), 1 in 32 (54%), and 2 in 16 (28%) patients. In 44 (75%) patients, CP was used as a first-line R/M regimen. Median number of cycles was five (range: 1-29). Dose modifications were necessary in 27 (46%) patients. The objective response rate was 47.5%, with 27 (45.8%) partial responses and one (2%) complete response. With a median follow-up of 13.4 months, median progression-free (PFS) and overall survival (OS) were 7.7 and 13.2 months, respectively. On multivariable analysis, an ECOG of 2 of 3 was associated with inferior OS (hazard ratio [HR]: 3.94; P = 0.01; 95% confidence interval [CI]: 1.1-14.04) and PFS (HR: 7.29; P < 0.01; 95% CI: 2.1-26.0) compared to an ECOG 0 of 1. First-line CP administration was associated with superior PFS compared to second line (HR: 2.6; P = 0.02; 95% CI:1.2-5.5). CP is well tolerated in this population of patients, with favorable tumor efficacy. First-line use and an ECOG 0 of 1 points appears to confer superior outcomes. 4. Laryngoscope, 127:1583-1588, 2017.

Anti-epidermal growth factor receptor therapy for advanced head and neck squamous cell carcinoma: a meta-analysis

To assess the efficacy and safety of anti-epidermal growth factor receptor (EGFR) therapy versus non-anti-EGFR therapy for advanced head and neck squamous cell carcinoma (HNSCC). The Cochrane Central Register of Controlled Trials, Medline, and Embase databases were searched for relevant reports. Quantitative analysis was carried out to evaluate the overall response rate (ORR), overall survival (OS), progression free survival (PFS), and grade 3-4 adverse effects. Ten reports involving 2,396 patients were included. Primary meta-analysis indicated that anti-EGFR therapy could improve ORR [relative risk (RR) 1.36, 95% confidence interval (CI) 1.12-1.67] and PFS [hazard ratio (HR) 0.63, 95% CI 0.55-0.71), but failed to improve OS (HR 0.88, 95% CI 0.74-1.03). In subgroup analyses, we found that monoclonal antibodies (Mabs) could improve ORR, OS, and PFS for both locoregionally advanced (LA) (ORR: 1.21, 1.08-1.37; OS: 0.72, 0.59-0.89; PFS: 0.66, 0.53-0.83) and recurrent/metastatic (RM) HNSCC (ORR: 1.88, 1.40-2.54; OS: 0.79, 0.67-0.94; PFS: 0.61, 0.52-0.71), while tyrosine kinase inhibitors (TKIs) did not improve any of these in patients with either LA (ORR: 1.09, 0.91-1.32; OS: 0.7, 0.31-1.63; PFS: 0.71, 0.34-1.52) or RM (ORR: 1.65, 0.84-3.24; OS: 1.13, 0.97-1.31; PFS: not available) HNSCC. Analysis of adverse effects demonstrated that rash (RR 14.34, 95% CI 5.02-41.02), diarrhea (2.36, 1.15-4.87), and anorexia (2.49, 1.11-5.56) were significantly associated with anti-EGFR therapy. Anti-EGFR Mabs are effective for both LA and RM HNSCC. In contrast, TKIs were unsuitable for treatment of advanced HNSCC. During anti-EGFR therapy, rash and some gastrointestinal reactions, such as diarrhea and anorexia, should be carefully monitored.

Paclitaxel (TLX) and cetuximab (CTX) combination efficiency after failure of a platinum-based chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC).

5549 Background: Platinum-based chemotherapy is the current standard in first line treatment of RMHNSCC. CTX is known to be efficient alone (objective response rate ORR=10-13%) or combined with pla...