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Introduction: Squamous cell carcinoma of the head and neck (SCCHN) is a multifactorial disease involving genetic and environmental factors representing one of the most frequent cancer-related deaths worldwide. Tobacco and alcohol use account for most SCCHN, while a growing subset of oropharyngeal cancers is causally associated with human papillomavirus (HPV) infection. Despite improvements in overall survival, patients with HPV-negative locally advanced (LA) SCCHN continue to have a poor prognosis. For these patients, the standard of care is radiotherapy with concurrent chemotherapy (RCT)., Methods: This retrospective, multicenter, and observational study analyzed the treatment compliance of 326 patients with LA-SCCHN who underwent RCT between January 1st, 2014, and June 30th, 2017. This study also evaluated the potential factors associated with treatment compliance, the compliance impact on clinical response, and the main toxicities experienced by patients., Results: A total of 274 (84%) patients were compliant and received the planned dose of cisplatin. Overall, 957 adverse events were reported in 98.2% of patients during the study. The overall response rate was 80.2%, with 60.4% of patients achieving a complete response., Discussion: Despite the high treatment compliance, 62.6% of adverse events reported were related to cisplatin. Identifying risk factors associated with non-compliance could enable physicians to identify ineligible patients for cisplatin-based RCT and prevent patients from receiving inadequate treatment leading to severe adverse events.., Competing Interests: Merck KGaA, Darmstadt, Germany, reviewed the manuscript for medical accuracy only before the journal submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors. AV: received a grant from Merck for the execution of this study. GC: received grants as a speaker from AstraZeneca, Bristol-Myers-Squibb, Merck Serono, Merck Sharp Dohme; participation in Advisory Boards from AstraZeneca, Bristol-Myers-Squibb, Merck Serono, Merck Sharp Dohme; principal investigator in sponsored trials: AstraZeneca, Bristol-Myers-Squibb, Merck Serono, Merck Sharp Dohme, GlaxoSmithKline; travel and/or accommodations: AstraZeneca, Merck Serono, Merck Sharp Dohme. TdO: received grants as a speaker from Merck, MSD, and Astra Zeneca advisory boards and travel grants from MSD, Sanofi, and Roche. AC: received travel grants from Merck and MSD. LR: received travel grants and participated in advisory boards and oncology education programs from MSD, Merck, BMS, Roche, and Novartis. AP: served as an advisor for MSD, Nanobiotics, BMS, AstraZeneca, and Merck Serono and received institutional research funding from BMS, Merck Serono, Roche, and Sanofi. NM: participated on Merck and MSD advisory boards. MS: participated on BMS advisory board and received travel grants from MSD. RG: participated on MSD and Merck advisory boards, received honoraria as a speaker for Merck and MSD, and travel grants from MSD, BMS, and Merck. LR: received travel grants from Merck and MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Varges Gomes, Castro, de Oliveira, Colmenero, Ribeiro, Psyrri, Magné, Plana Serrahima, Marinho, Giglio, Iglesias Rey, Angel and Macedo.)

Objectives: The aim of this study was to confirm the efficacy of the ERBITAX scheme (paclitaxel 80 mg/m 2 weekly and cetuximab 400 mg/m 2 loading dose, and then 250 mg/m 2 weekly) as first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) who are medically unfit for cisplatin-based (PT) chemotherapy., Materials and Methods: This retrospective, non-interventional study involved 16 centers in Spain. Inclusion criteria were to have started receiving ERBITAX regimen from January 2012 to December 2018; histologically confirmed SCCHN including oral cavity, oropharynx, hypopharynx, and larynx; age ≥18 years; and platinum (PT) chemotherapy ineligibility due to performance status, comorbidities, high accumulated dose of PT, or PT refractoriness., Results: A total of 531 patients from 16 hospitals in Spain were enrolled. The median age was 66 years, 82.7% were male, and 83.5% were current/former smokers. Patients were ineligible to receive PT due to ECOG 2 (50.3%), comorbidities (32%), PT cumulative dose ≥ 225 mg/m 2 (10.5%), or PT refractoriness (7.2%). Response rate was 37.7%. Median duration of response was 5.6 months (95% CI: 4.4-6.6). With a median follow-up of 8.7 months (95% CI: 7.7-10.2), median PFS and OS were 4.5 months (95% CI: 3.9-5.0) and 8.9 months (95% CI: 7.8-10.3), respectively. Patients treated with immunotherapy after ERBITAX had better OS with a median of 29.8 months compared to 13.8 months for those who received other treatments. The most common grade ≥ 3 toxicities were acne-like rash in 36 patients (6.8%) and oral mucositis in 8 patients (1.5%). Five (0.9%) patients experienced grade ≥ 3 febrile neutropenia., Conclusion: This study confirms the real-world efficacy and tolerability of ERBITAX as first-line treatment in recurrent/metastatic SCCHN when PT is not feasible. Immunotherapy after treatment with ERBITAX showed remarkable promising survival, despite potential selection bias., Competing Interests: JR-C: Advisory role: Sanofi, Novartis and Merck. BCC: Support for this manuscript from Merck through TTCC Group. Speaker on behalf of BMS, MSD, and Merck. Meeting support from BMS and MSD. Member of TTCC Group unpaid. MP: Speaker on behalf of BMS. Meeting support from MSD Oncology. AG: Advisory board from MSD and Bristol Myers Squibb. AC: Speaker on behalf of Merck. Meeting support from Merck. LI: Speaker on behalf of Merck, MSD, Roche, Bayer, Eisai. Meeting support from Merck and MSD. Advisory board from Merck MSD, Roche, Lilly, and Ipsen. PP: Received grants from BMS, Merck, and MSD. Consulting fees from BMS, Merck, and MSD. Speaker on behalf of BMS, Merck, and MSD. Meeting support from BMS, Merck, and MSD. Member of TTCC Group. IC: Speaker on behalf of MSD, Merck, Roche, BMS, Seagen, and Pfizer. Meeting support in Pfizer, MSD, and Merck. CP: Speaker on behalf of Novartis, Merck, and MSD. Meeting support from Novartis, Merck, and MSD. IH: Speaker on behalf of Pierre Fabre educational event and Merck lecture. Meeting support from Merck support for an event and AztraZeneca support for educational expertise. MC: Participated in and received equipment for clinical trials from the institution. Speaker on behalf of MSD and Merck. Meeting support from MSD and Merck. EO: Speaker on behalf of GSK, AstraZeneca, Clovis, Merck, Pharmamar, and MSD. Expert testimony for GSK. Meeting support from Merck and MSD. Advisory board for Eisai. RM: Support for this manuscript from Merck for medical writing and article processing charges. Speaker on behalf of MSD and Merck. Meeting support from BMS, Merck, and MSD. Advisory board for MSD, Merck, Boehringer, Bayer, Roche, Nanobiotics and Sigean. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rubió-Casadevall, Cirauqui Cirauqui, Martinez Trufero, Plana Serrahima, García Castaño, Carral Maseda, Iglesias Docampo, Pérez Segura, Ceballos Lenza, Gutiérrez Calderón, Fuster Salvà, Pena Álvarez, Hernandez, del Barco Morillo, Chaves Conde, Martínez Galán, Durán Sánchez, Quiroga, Ortega and Mesia.)

Objectives: Induction chemotherapy (ICT) followed by definitive treatment is an accepted non-surgical approach for locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, ICT remains a challenge for cisplatin-unfit patients. We evaluated paclitaxel and cetuximab (P-C) as ICT in a cohort of LA-HNSCC patients unfit for cisplatin., Materials and Methods: This is a retrospective analysis of patients with newly diagnosed LA-HNSCC considered unfit for cisplatin-based chemotherapy (age >70 and/or ECOG≥2 and/or comorbidities) treated with weekly P-C followed by definitive radiotherapy and cetuximab (RT-C) between 2010 and 2017. Toxicity and objective response rate (ORR) to ICT and RT-C were collected. Median overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Cox regression analysis was performed to determine baseline predictors of OS and PFS., Results: A total of 57 patients were included. Grade 3-4 toxicity rate to ICT was 54.4%, and there was a death deemed treatment-related (G5). P-C achieved an ORR of 66.7%, including 12.3% of complete responses (CR). After P-C, 45 patients (78.9%) continued with concomitant RT-C. Twenty-six patients (45.6%) achieved a CR after definitive treatment. With a median follow-up of 21.7 months (range 1.2-94.6), median OS and PFS were 22.9 months and 10.7 months, respectively. The estimated 2-year OS and PFS rates were 48.9% and 33.7%, respectively. Disease stage had a negative impact on OS (stage IVb vs. III-IVa: HR = 2.55 [1.08-6.04], p = 0.03), with a trend towards worse PFS (HR = 1.92 [0.91-4.05], p = 0.09). Primary tumor in the larynx was associated with improved PFS but not OS (HR = 0.45 [0.22-0.92], p = 0.03, and HR = 0.69 [0.32-1.54], p = 0.37, respectively)., Conclusion: P-C was a well-tolerated and active ICT regimen in this cohort of LA-HNSCC patients unfit for cisplatin-based chemotherapy. P-C might represent a valid ICT option for unfit patients and may aid patient selection for definitive treatment., Competing Interests: OM: Advisory Role: Merck and Bristol Myers Squibb. Financial Interests, Personal, Other, Travel/Accommodation expenses: MSD Oncology, Merck, Bristol Myers Squibb, and Transgene. Personal and/or Institutional Research Grant: GlaxoSmithKline and Roche. Financial Interests, Personal, and/or Institutional Research Grant: Bristol-Myers Squibb, Merck, MSD Oncology, Isa Therapeutics, AXL Oncology, Boehringer Ingelheim, Roche, Debiopharm, Abbvie, and Ayala Therapeutics. C-CS reports advisory role for Merck KGaA and Bristol-Myers Squibb; grant/research support (clinical trials) from AstraZeneca, Merck Sharp & Dohme, Pfizer, and Merck KGaA; travel and academic expenses from Merck KGaA, Bristol-Myers Squibb, and Merck Sharp & Dohme. PM reports consultant role for Nanobiotix and travel non-financial support and academic work fees from Merck, Eisai, and Bristol-Myers Squibb. TM reports consultant role for MSD, Merck, and Nanobiotics; speaker’s bureau for Bristol-Myers Squibb, MSD, AstraZeneca, and Merck; and travel and academic work fees from Merck and MSD. MR reports consultant role for BMS, MSD, Merck, Astra Zeneca, Nanobiotics, Roche, and Bayer; speaker’s bureau for BMS, MSD, Roche, and Merck; and travel and academic work fees from Roche, BMS, and Merck. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marín-Jiménez, Oliva, Peinado Martín, Cabezas-Camarero, Plana Serrahima, Vázquez Masedo, Lozano Borbalas, Cabrera Martín, Esteve, Iglesias Moreno, Vilajosana Altamis, Arribas Hortigüela, Taberna Sanz, Pérez-Segura and Mesía.)

Background: Sequential treatment of Panitumumab (Pb) plus Paclitaxel (Px) as induction treatment (IT) followed by concurrent bioradiotherapy (Bio-RT) with Pb may be an alternative for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) in patients ineligible for high-dose cisplatin therapy., Methods: Phase II, single-arm, multicentre study, with two-stage design, in patients ≥ 18 years with stage III-IVa-b LA-SCCHN unfit for platinum. Patients received Px + Pb (9 weeks) as IT followed by Bio-RT + Pb. Primary endpoint: overall response rate (ORR) after IT, defined as: more than 70% of patients achieving complete response (CR) or partial response (PR) to IT. Secondary end-points: progression-free survival, organ preservation rate, safety profile., Results: Study ended prematurely (51 patients) due to slow recruitment. ORR: 66.7% (95% CI: 53.7-79.6), 8 (15.7%) CR and 26 (51.0%) PR. 39 patients (76%) completed radiotherapy (RT). Pb and/or Px-related adverse events (AEs) grade 3-4: 56.9% during IT and 63.4% during the concomitant phase, of which most common were skin toxicity (33.3%). Five deaths occurred during treatment, two of them (3.9%) were Pb and/or Px-related., Conclusions: Although underpowered, ORR was higher than the pre-specified boundary for considering the treatment active. Although Px + Pb as IT provides some benefit, the safety profile is worse than expected. To consider Pb + Px as IT as an alternative for platinum-unsuitable LA-SCCHN, further research/investigation would be needed.