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Patients with cancer (PC) are at high risk of acquiring COVID-19 and can develop more serious complications. Deeper understanding of vaccines immunogenicity in this population is crucial for adequately planning vaccines programs. The ONCOVac study aimed to comprehensively assess the immunogenicity of mRNA-1273 vaccine in terms of humoral and cellular response.We conducted a prospective, single-center study including patients with solid tumours treated with cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i), immunotherapy (IT) or chemotherapy (CT). Patients were enrolled previously to vaccination with mRNA-1273. We also involved health care workers (HCW) to serve as a control group. We took blood samples before first dose administration (BL), after first dose (1D), and after second dose (2D). The primary objective was to compare the rate and magnitude of T cell response after second dose whereas safety and humoral response were defined as secondary objectives. We also collected patient reported outcomes after both the first and second vaccine dose and a six-month follow-up period to diagnose incident COVID-19 cases was planned.The rate of specific anti-S serologic positivity (anti-S IgG cut-off point at 7,14 BAU/mL) was significantly higher in HCW compared to PC after 1D (100% versus 83.8%; p = 0.04), but similar after 2D (100% versus 95.8%; p = 0.5). This difference after 1D was driven by PC treated with CT (100% versus 64.5%; p = 0.001). Cellular response after 2D was significantly lower in PC than in HCW for both CD4+ (91.7% versus 59.7%; p = 0.001) and CD8+ (94.4% versus 55.6%; p 0.001) T cells. We found a difference on pre-existing CD4+ T cell response in HCW comparing to PC (36% and 17%, p = 0.03); without difference in pre-existing CD8+ T cell response (31% and 23%, p = 0.5). After excluding patients with pre-existing T cell response, PC achieved even lower CD4+ (50.9% versus 95.5%, p 0.001) and CD8+ (45.5% versus 95.5%, p 0.001) T cell response compared with HCW. Regarding safety, PC reported notably more adverse events than HCW (96.6% versus 69.2%, p 0.001).We demonstrated that PC showed a similar humoral response but a lower T cell response following two doses of mRNA-1273 vaccination. Further studies are needed to complement our results and determine the implication of low T cell response on clinical protection of PC against COVID-19.

To evaluate the efficacy and safety of cobimetinib plus atezolizumab in the treatment of patients with advanced BRAFThis phase 1b, open-label, international multicentre study enrolled 3 cohorts. Herein, we report on patients in cohorts A and B who had progressed on prior anti‒PD-1 therapy. Patients in cohort A received cobimetinib 60 mg once daily for 21 days followed by a 7-day break and concurrent intravenous atezolizumab 840 mg every 2 weeks. Patients in cohort B received the same dosing regimen as cohort A except for cycle 1 in which patients received cobimetinib only for the first 14 days prior to initiation of atezolizumab on cycle 1 day 15. Coprimary end-points were objective response rate and disease control rate. Secondary end-points were duration of response, progression free survival and overall survival.Between 19th June 2017 and 12th December 2018, 103 patients were enrolled. Median follow-up was 6.9 months (interquartile range, 4.8-10.1 months); objective response rate was 14.6% and disease control rate was 38.8% (95% confidence interval, 29.39-48.94). The median duration of response, progression-free survival and overall survival was 12.7 months, 3.8 months and 14.7 months, respectively. The most common adverse events were diarrhoea (75/103; 72.8%), dermatitis acneiform (57/103; 55.3%) and nausea (52/103; 50.5%). Thirty-four patients (33.0%) died: 33 (91.7%) due to progressive disease and one (1%) due to treatment-related oesophagitis.Combination therapy with cobimetinib and atezolizumab in patients with advanced BRAFThis study is registered with ClinicalTrials.gov; NCT03178851.

Considerables avances se han vivido en los últimos años, tanto en el conocimiento de la biología del melanoma como en el desarrollo de nuevas terapias médicas que han acreditado ser muy activas, capaces no sólo de inducir respuestas clínicas y radiológicas, sino también de controlar la enfermedad a largo plazo. Más aún, los resultados actualizados de los ensayos fase 3 randomizado en pacientes con enfermedad avanzada o de alto riesgo, han hecho a muchos investigadores especular sobre la posibilidad de que se haya conseguido incluso curar a algunos pacientes. No se puede obviar que los resultados actuales se han precedido de numerosos años de fracasos en la investigación médica con quimioterapia y bioquimioterapia, de varias décadas de investigación y refinamiento en las técnicas quirúrgicas que demostraron ser curativas para la enfermedad localizada y, literalmente, de centurias de perplejidad, ante una enfermedad desconcertante por su comportamiento y agresividad clínica. Presentamos una breve revisión histórica del conocimiento del melanoma, desde una perspectiva médico quirúrgica, con el objetivo que despertar en el lector el interés por avanzar en el conocimiento del pasado y sobre todo del futuro de una patología tumoral, que hasta hace muy poco no tenía opciones terapéuticas, pero que ha abierto las puertas para la innovación terapéutica en oncología.

Epstein Barr virus; Prognosis; Response to treatment Virus de Epstein Barr; Pronóstico; Respuesta al tratamiento Virus d'Epstein Barr; Pronòstic; Resposta al tractament The treatment of head and neck and salivary gland tumours is complicated and evolves constantly. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein–Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms. In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica—SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica—SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers. SEOM and SEAP acknowledge the financial support for this project in the form of unrestricted collaboration in the logistics from AstraZeneca.

La Revista Ciencias y Artes, comprometida con la producción y difusión del conocimiento académico, pone a disposición de la comunidad académica, un nuevo número, con contenido de análisis teórico de actualidad sobre ciencias sociales y humanidades, de interés para profesionales, estudiantes de posgrado, pregrado y público en general, que desee ampliar sus conocimientos a partir de la información científica que ha sido previamente arbitrada.

Immune checkpoint inhibitors (ICI) have been associated with several immune-related adverse events, including sarcoidosis-like reactions (SLR). SLR, which has a low prevalence but an increasing incidence, is similar to sarcoidosis in terms of histology, and clinical and radiological manifestations. The most commonly affected organs are hilar and mediastinal lymph nodes and skin. SLR is an exclusion diagnosis, so a lymph node biopsy can be useful to distinguish between tumor progression and SLR, particularly in tumors in which nodal involvement is very common.We performed a retrospective analysis of SLR in all cancer patients receiving ICIs in our institution between January 2016 and June 2020.Among the 1063 treated patients, seven experienced SLR, four of whom were symptomatic (cough, skin lesions, arthralgia), with time to onset ranging from 1.5 to 6.7 months after ICI initiation. All seven patients had bilateral hilar lymphadenopathy, and granulomatous reactions in five of the six patients with lymph node biopsies. SLR improved in all patients, including four patients who continued with ICI. Three patients received corticosteroids and/or stopped ICI therapy. Four of these patients had partial responses at the time SLR was identified.Management of SLR lacks a consensus recommendation, although corticosteroids and/or stopping the ICI are generally implemented. The potential consequences of stopping anticancer treatment should be taken into consideration, particularly in the absence of clear management recommendations.

Intratumoral therapies, especially Toll-like receptor agonists, can trigger both the innate and adaptive immune systems. BO-112 is a nanoplexed form of polyinosinic:polycytidylic acid (poly I:C) that induces local and systemic immunotherapeutic effects in mouse models. In a multicenter phase 1 clinical trial, repeated intratumoral administrations of BO-112 induced an increase in tumor cell necrosis and apoptosis, as well as augmented immune reactivity according to gene expression profiling. The first three cohorts receiving BO-112 as a monotherapy resulted in a recommended dose of 1 mg that could be safely repeated. Two grade 3 to 4 adverse reactions in the form of reversible thrombocytopenia were reported. In a fourth cohort of 28 patients with tumors that had primary resistance to anti-programmed cell death protein-1 (PD-1), the combination of intratumoral BO-112 with nivolumab or pembrolizumab was also well tolerated, and 3 patients (2 with melanoma and 1 with renal cell carcinoma) achieved partial responses, with 10 more patients having stable disease at 8 to 12 weeks. Thus, local BO-112 combined with a systemic anti-PD-1 agent might be a strategy to revert anti-PD-1 resistance.

Background Treatment options for patients (pts) with BRAFV600 wild type advanced melanoma following failure on anti–programmed death receptor 1 (aPD-1) therapy are limited. Melanoma is strongly driven by MAPK signaling. The MEK inhibitor cobimetinib inhibits MAPK signaling and increases immune cell infiltrate in the tumor, providing a strong rationale for combining cobimetinib with the anti–PD ligand-1 (PD-L1) antibody atezolizumab. Methods This multisite, phase Ib study enrolled pts with BRAFV600 wild type advanced melanoma with disease progression on or after aPD-1 therapy (≤12 weeks before study entry) to 2 cohorts. In cohort A, pts received oral cobimetinib 60 mg (once daily, 21 days on, 7 days off) and IV atezolizumab 840 mg (every 2 weeks). In cohort B, pts received identical treatment except in cycle 1, in which cobimetinib was dosed alone for the first 14 days. Paired pretreatment and during-treatment (cycle 2) tumor biopsies were mandated in cohort B. The co-primary endpoints were confirmed objective response rate per RECIST v1.1 and disease control rate (DCR; complete response, partial response [PR], or stable disease [SD] at 16 weeks). Safety was a secondary endpoint (CTCAE v4.0). Results At data cutoff (March 1, 2019), 103 pts were enrolled in cohorts A (n = 92) and B (n = 11); 50 pts had >16 weeks of follow-up and were included in this analysis. Of these 50 pts, 8 (16%) had PR as best confirmed response and 18 (36%) had SD; the DCR was 38% (PR = 8; SD at 16 weeks=11). Prior aPD-1 therapy in 9 pts with unconfirmed PR included pembrolizumab (n = 5), nivolumab (n = 1), pembrolizumab + ipilimumab (n = 2), or nivolumab + ipilimumab (n = 1). For the 7 pts with confirmed PR whose tumor PD-L1 status could be established, 6 were positive (≥1% PD-L1+ cells) and 1 was negative ( Conclusions Preliminary efficacy and safety data for the combination of cobimetinib and atezolizumab in pts who have disease progression on/after prior aPD-1 therapy suggest that this is a feasible and active option warranting further exploration. Clinical trial identification NCT03178851. Editorial acknowledgement ApotheCom, Yardley, PA, USA. Legal entity responsible for the study Roche. Funding Roche. Disclosure S.K. Sandhu: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy: Merck Sharp and Dohme; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Research grant / Funding (institution): Endocyte. V.G. Atkinson: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Travel / Accommodation / Expenses: Onco-Sec. M. Gonzalez Cao: Honoraria (self), Honoraria (institution), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (institution), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (institution): MSD; Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Takeda. T. Medina: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Array; Research grant / Funding (institution): Dynavax; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Checkmate. A. Soria Rivas: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono. I. Caro: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche Genentech. L. Roberts: Full / Part-time employment: Genentech. Y. Song: Full / Part-time employment: Roche/Genentech. Y. Yan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/Genentech. G.V. Long: Advisory / Consultancy: Aduro; Advisory / Consultancy: Amgen; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Mass-Array; Advisory / Consultancy: Merck Sharp and Dohme; Advisory / Consultancy: Novartis; Advisory / Consultancy: Oncosec; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche.