TTCC-2019-02: real-world evidence of first-line cetuximab plus paclitaxel in recurrent or metastatic squamous cell carcinoma of the head and neck

ObjectivesThe aim of this study was to confirm the efficacy of the ERBITAX scheme (paclitaxel 80 mg/m2 weekly and cetuximab 400 mg/m2 loading dose, and then 250 mg/m2 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 methodsThis 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.ResultsA 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/m2 (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.ConclusionThis 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

Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): A randomised, double-blind, phase 3 trial

Background: Dacomitinib is an irreversible pan-EGFR family tyrosine kinase inhibitor. Findings from a phase 2 study in non-small cell lung cancer showed favourable efficacy for dacomitinib compared with erlotinib. We aimed to compare dacomitinib with erlotinib in a phase 3 study. Methods: In a randomised, multicentre, double-blind phase 3 trial in 134 centres in 23 countries, we enrolled patients who had locally advanced or metastatic non-small-cell lung cancer, progression after one or two previous regimens of chemotherapy, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and presence of measurable disease. We randomly assigned patients in a 1:1 ratio to dacomitinib (45 mg/day) or erlotinib (150 mg/day) with matching placebo. Treatment allocation was masked to the investigator, patient, and study funder. Randomisation was stratified by histology (adenocarcinoma vs non-adenocarcinoma), ethnic origin (Asian vs non-Asian and Indian sub-continent), performance status (0-1 vs 2), and smoking status (never-smoker vs ever-smoker). The coprimary endpoints were progression-free survival per independent review for all randomly assigned patients, and for all randomly assigned patients with KRAS wild-type tumours. The study has completed accrual and is registered with ClinicalTrials.gov, number NCT01360554. Findings: Between June 22, 2011, and March 12, 2013, we enrolled 878 patients and randomly assigned 439 to dacomitinib (256 KRAS wild type) and 439 (263 KRAS wild type) to erlotinib. Median progression-free survival was 2.6 months (95% CI 1.9-2.8) in both the dacomitinib group and the erlotinib group (stratified hazard ratio [HR] 0.941, 95% CI 0.802-1.104, one-sided log-rank p=0.229). For patients with wild-type KRAS, median progression-free survival was 2.6 months for dacomitinib (95% CI 1.9-2.9) and erlotinib (95% CI 1.9-3.0; stratified HR 1.022, 95% CI 0.834-1.253, one-sided p=0.587). In patients who received at least one dose of study drug, the most frequent grade 3-4 adverse events were diarrhoea (47 [11%] patients in the dacomitinib group vs ten [2%] patients in the erlotinib group), rash (29 [7%] vs 12 [3%]), and stomatitis (15 [3%] vs two [Interpretation: Irreversible EGFR inhibition with dacomitinib was not superior to erlotinib in an unselected patient population with advanced non-small-cell lung cancer or in patients with KRAS wild-type tumours. Further study of irreversible EGFR inhibitors should be restricted to patients with activating EGFR mutations. Funding: Pfizer.</p

CheckMate 141: 1-Year Update and Subgroup Analysis of Nivolumab as First-Line Therapy in Patients with Recurrent/Metastatic Head and Neck Cancer

Nivolumab significantly improved overall survival (OS) vs investigator's choice (IC) of chemotherapy at the primary analysis of randomized, open-label, phase 3 CheckMate 141 in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). Here, we report that OS benefit with nivolumab was maintained at a minimum follow-up of 11.4 months. Further, OS benefit with nivolumab vs IC was also noted among patients who received first-line treatment for R/M SCCHN after progressing on platinum therapy for locally advanced disease in the adjuvant or primary (i.e., with radiation) setting. 2018

Exploratory analysis of front-line therapies in REVEL: a randomised phase 3 study of ramucirumab plus docetaxel versus docetaxel for the treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy.

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. 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. 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. 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. NCT01168973

Una revisión sistemática de las recomendaciones diagnósticas y terapéuticas del panel de expertos en cáncer de origen desconocido

Cancer of Unknown Primary (CUP) is a metastatic cancer with confirmed histology of which the primary origin is unknown after to work up initial evaluation through a pathological clinical study, the analytical and imaging study. The diagnostic process includes the early obtaining of quality biopsy material. It includes its histological and immunohistochemical analysis: a study to determine the tumor line, an analysis of cytokeratins and a large battery of antibodies to confirm the specific origin of each possible tumor type. The development of molecular platforms has allowed improving the diagnosis of CUP, increasing the number of patients who can benefit from treatment with specific therapy, significantly increasing the survival and reducing the toxicity. However, the updated guidelines (NICE, ESMO, NCCN) emphasize that the impact on the clinical benefit of the specific treatment according to the results of the molecular platforms is still controversial.El Cáncer de Origen Desconocido (COD) es un cáncer metastásico con histología confirmada del cual se desconoce el origen primario después de realizar un estudio diagnóstico inicial mediante el estudio clínico patológico, el estudio analítico y de imagen. El estudio diagnóstico incluye la obtención precoz de material de biopsia de calidad. Incluye su análisis histológico e inmunohistoquímico: un estudio para determinar la estirpe tumoral, análisis de citoqueratinas y una batería amplia de anticuerpos para confirmar el origen específico. El desarrollo de plataformas moleculares ha mejorado su diagnóstico, incrementando el número de pacientes que se benefician del tratamiento con terapia específica, aumentando su supervivencia y reduciendo la toxicidad. Sin embargo, las guías actualizadas (NICE, ESMO, NCCN) destacan que el impacto en el beneficio clínico del tratamiento específico según los resultados de las plataformas moleculares es todavía controvertido