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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. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) is defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than 90% of these tumours have squamous histology. In an effort to incorporate evidence obtained since 2013 publication, Spanish Society of Medical Oncology (SEOM) presents an update of HNC diagnosis and treatment guideline. The eighth edition of TNM classification, published in January 2017, introduces important changes for p16-positive oropharyngeal tumours, for lip and oral cavity cancer and for N3 category. In addition, there are new data about induction chemotherapy and the role of immunotherapy in HNC. [ABSTRACT FROM AUTHOR]

Background: Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition.Methods: In this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life.Results: The median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to 6.0) in the group that received standard therapy. Overall survival was significantly longer with nivolumab than with standard therapy (hazard ratio for death, 0.70; 97.73% CI, 0.51 to 0.96; P=0.01), and the estimates of the 1-year survival rate were approximately 19 percentage points higher with nivolumab than with standard therapy (36.0% vs. 16.6%). The median progression-free survival was 2.0 months (95% CI, 1.9 to 2.1) with nivolumab versus 2.3 months (95% CI, 1.9 to 3.1) with standard therapy (hazard ratio for disease progression or death, 0.89; 95% CI, 0.70 to 1.13; P=0.32). The rate of progression-free survival at 6 months was 19.7% with nivolumab versus 9.9% with standard therapy. The response rate was 13.3% in the nivolumab group versus 5.8% in the standard-therapy group. Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of the patients in the nivolumab group versus 35.1% of those in the standard-therapy group. Physical, role, and social functioning was stable in the nivolumab group, whereas it was meaningfully worse in the standard-therapy group.Conclusions: Among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy. (Funded by Bristol-Myers Squibb; CheckMate 141 ClinicalTrials.gov number, NCT02105636 .). [ABSTRACT FROM AUTHOR]

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: Concurrent chemoradiotherapy is the standard treatment for patients with unresectable, locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN); induction chemotherapy (ICT) may provide survival benefits in some patients. This study aimed to demonstrate the noninferiority of concomitant cetuximab plus radiotherapy (cet+RT) vs cisplatin plus radiotherapy (cis+RT) in patients with unresectable LA-SCCHN who were responsive to ICT., Materials and Methods: This randomized, open-label, phase 3 trial studied patients with unresectable LA-SCCHN who received 3 cycles of ICT (docetaxel, cisplatin, and 5-fluorouracil; TPF) followed by cis+RT (standard arm) or cet+RT (experimental arm). The primary endpoint was noninferiority of the experimental arm vs the standard arm in terms of overall survival (OS), based on a hazard ratio (HR) of < 1.3. Secondary endpoints included progression-free survival, overall response, safety, and quality of life (QOL)., Results: Between July 15, 2008, and July 5, 2013, 519 patients were recruited and started ICT; 407 patients received post-ICT treatment (cis+RT, n = 205; cet+RT, n = 202). At a median follow-up of 43.9 (cis+RT) and 41.1 (cet+RT) months, median OS was 63.6 and 42.9 months with cis+RT and cet+RT, respectively (HR [90% CI] = 1.106 [0.888-1.378], P =.4492). There were no differences in progression-free survival, overall response rates, or adverse event rates between groups. There was greater late neurotoxicity with cis+RT than cet+RT (P =.0058). Several QOL dimensions improved with cet+RT vs cis+RT (physical functioning, P =.0287; appetite loss, P =.0248; social contact, P =.0153)., Conclusion: Noninferiority of cet+RT over cis+RT was not demonstrated., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ricard Mesía has served in an advisory role for Astra-Zeneca; Bayer; Bristol Myers Squibb; Merck KGaA, Darmstadt, Germany; MSD; Nanobiotix; Pfizer; Roche, and Seattle Genetics and has received speaker’s bureau compensation from Bristol Myers Squibb, Merck KGaA, and MSD. Miren Taberna has served in an advisory role for Merck KGaA, MSD, and Nanobiotix and has received speaker’s bureau compensation from Astra Zeneca, Bristol Myers Squibb, Merck KGaA, and MSD. Beatriz Cirauqui has served in an advisory or consultant role for Bristol Myers Squibb, Merck KGaA, and Roche and has received speaker’s bureau compensation from Bristol Myers Squibb, Eisai, and Roche. Lara Iglesias Docampo has served in an advisory role for Bayer, Bristol Myers Squibb, Lilly, Merck KGaA, MSD, and Roche and has received personal fees from Eisai and Sanofi. Jordi Rubió-Casadevall has served in an advisory role for Novartis, (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Hand-foot syndrome (HFS) is a common adverse reaction associated with capecitabine chemotherapy that significantly affects the quality of life of patients. This study evaluates the safety and effectiveness of a topical heparin (TH) treatment on the clinical manifestations and anatomopathological alterations of capecitabine-induced HFS. In addition, we performed proteome profiling of skin biopsies obtained from patients with HFS at baseline and after heparin treatment., Methods: Patients with grade ⩽ 2 HFS associated with capecitabine were included in this study. The primary end point was the effectiveness of TH in reducing HFS of any grade. Clinical improvement was evaluated by clinicians, and an improvement was perceived by patients who performed a weekly visual analog scale questionnaire. Secondary end points included a comparative histological analysis and protein expression in skin biopsies at baseline and after 3 weeks of HT treatment. Proteomic profiling was carried out using quantitative isobaric labelling and subsequently validated by a T-array., Results: Twenty-one patients were included in the study. The median TH treatment time was 7.6 weeks (range = 3.6-41.6 weeks), and the median response time was 3.01 weeks (95% CI = 2.15-3.97). At the end of treatment, 19 of 21 patients (90.48%) responded to treatment with a decrease in one or more grades of HFS. None of the patients experienced adverse effects related to TH usage, nor did they suspend chemotherapy treatment. The main findings observed in skin biopsies after treatment were a decrease in hyperkeratosis and lymphocytic infiltrates. The proteomic analysis showed altered expression of 34 proteins that were mainly related to wound healing, cell growth, and the immune response., Conclusion: Based on our results, topical heparin is an effective and safe treatment for clinical manifestations of HFS, probably due to the restauration of skin homeostasis after heparin treatment, as supported by our proteomics-derived data., Trial Registration: EudraCT 2009-018171-13., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Introduction: Non-small-cell lung cancer (NSCLC) is a heterogeneous disease. Front-line therapy may affect responses to subsequent treatment regimens, thus influencing second-line therapy decision making. In the randomised phase 3 REVEL study, second-line ramucirumab plus docetaxel (ram+doc) versus docetaxel (doc) improved survival of patients with metastatic NSCLC. We explore efficacy, safety and quality-of-life (QoL) in REVEL based on front-line therapy., Methods: Patients were grouped by specific front-line therapy received. Overall survival (OS), progression-free survival (PFS), objective response rate, safety and QoL were assessed descriptively. Kaplan-Meier estimation and Cox proportional hazards modelling were used; frequencies reported in percentages., Results: Baseline characteristics of 1253 patients were generally well balanced between treatment arms within each front-line therapy subgroup. For patients with non-squamous disease (n=912), induction therapies included platinum-based chemotherapy plus a taxane (n=227; 25%) or pemetrexed (n=449; 49%), with (n=172; 19%) or without bevacizumab. For patients with squamous disease (n=328), induction therapies included platinum-based chemotherapy plus gemcitabine (n=176; 54%) or a taxane (n=69; 21%). A highly selected subgroup (n=127; 14%) received pemetrexed continuation maintenance therapy. Ram+doc improved median OS and PFS versus doc across front-line therapy subgroups, as reflected by HRs ranging from 0.78 to 0.91 and 0.66 to 0.92, respectively, similar to results in the overall intention-to-treat cohort (HRs: 0.86 and 0.76, respectively). High-grade treatment-emergent adverse events of special interest (including neutropenia, febrile neutropenia, leucopenia and hypertension) were generally higher in ram+doc-treated patients relative to doc-treated patients regardless of front-line therapy. No clear differences in safety or QoL were seen across front-line therapy subgroups; outcomes were consistent with those reported in the overall intention-to-treat cohort., Conclusions: Results of this exploratory analysis suggest that second-line ram+doc may be effective regardless of prior treatment with platinum-based chemotherapy plus a taxane, pemetrexed, gemcitabine or bevacizumab. Overall, ram+doc is clinically beneficial across a wide range of patients with metastatic NSCLC who have progressed after various front-line therapies., Trial Registration Number: NCT01168973., Competing Interests: Competing interests: The following authors declared conflicts of interests. GCC, AHZ, ABO, PL, KW, and VJS are full-time employees and stockowners of Eli Lilly and Company. EA is a former employee and stockowner of Eli Lilly and Company. EBG has received honoraria from Dracen and EMD Serono, and his institution has received research funding from AstraZeneca, Bristol Myers Squibb, Merck, Eli Lilly and Company, Novartis, Genentech, Dynavax, Iovance, Mirati, and Neon. GVS has received honoraria from Eli Lilly and Company, AstraZeneca, Clovis Oncology, Regeneron, Novartis, Merck Sharp and Dohme, Pfizer, and Roche and has served on the speaker’s bureaus of Eli Lilly and Company, AstraZeneca, Merck Sharp and Dohme, and Novartis. MR has received honoraria for lectures from and functions in an advisory/consulting role for Eli Lilly and Company, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Hoffman-La Roche, Merck, Novartis, and Pfizer. MT has received Advisory Board honoraria from AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Eli Lilly and Company, Merck Sharp and Dohme, Novartis, Roche, Takeda; speaker’s honoraria from Eli Lilly and Company, Merck Sharp and Dohme, Takeda; research funding from AstraZeneca, Bristol Myers Squibb, Celgene, Roche; and travel grants from Bristol Myers Squibb, Boehringer, Merck Sharp and Dohme, and Novartis. HK has received reimbursement for meeting expenses and/or has functioned in an advisory/consultancy role for Eli Lilly and Company, Genesis Pharma, GlaxoSmithKline, Merck, Novartis, Pfizer, and Roche and has received reimbursement for meeting expenses from Enorasis. J-HK serves in an advisory/consultancy role for and his institution has received grant funding for clinical trials from Eli Lilly and Company, including during the conduct of this study, and from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and Roche. OTB has received honoraria from Eli Lilly and Company, AstraZeneca, Boehringer Ingelheim (for research funding and advisory/consultancy role), GlaxoSmithKline (for research funding), Merck (for advisory/consultancy role), Novartis, Pfizer, and Roche (for research funding). MP has received honoraria for speaking, advisory and consultancy roles for Eli Lilly and Company., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)