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Background: First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum–etoposide) showed a significant improvement in overall survival versus platinum–etoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide alone. Methods: CASPIAN is an ongoing, open-label, sponsor-blind, randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide. Eligible patients were aged 18 years or older (20 years in Japan) and had treatment-naive, histologically or cytologically documented ES-SCLC, with a WHO performance status of 0 or 1. Patients were randomly assigned (1:1:1) in blocks of six, stratified by planned platinum, using an interactive voice-response or web-response system to receive intravenous durvalumab plus tremelimumab plus platinum–etoposide, durvalumab plus platinum–etoposide, or platinum–etoposide alone. In all groups, patients received etoposide 80–100 mg/m2 on days 1–3 of each cycle with investigator's choice of either carboplatin area under the curve 5–6 mg/mL/min or cisplatin 75–80 mg/m2 on day 1 of each cycle. Patients in the platinum–etoposide group received up to six cycles of platinum–etoposide every 3 weeks and optional prophylactic cranial irradiation (investigator's discretion). Patients in the immunotherapy groups received four cycles of platinum–etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks. The two primary endpoints were overall survival for durvalumab plus platinum–etoposide versus platinum–etoposide and for durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered at ClinicalTrials.gov, NCT03043872. Findings: Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinum–etoposide, 268 to durvalumab plus platinum–etoposide, and 269 to platinum–etoposide). As of Jan 27, 2020, the median follow-up was 25·1 months (IQR 22·3–27·9). Durvalumab plus tremelimumab plus platinum–etoposide was not associated with a significant improvement in overall survival versus platinum–etoposide (hazard ratio [HR] 0·82 [95% CI 0·68–1·00]; p=0·045); median overall survival was 10·4 months (95% CI 9·6–12·0) versus 10·5 months (9·3–11·2). Durvalumab plus platinum–etoposide showed sustained improvement in overall survival versus platinum–etoposide (HR 0·75 [95% CI 0·62–0·91]; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3–14·7) versus 10·5 months (9·3–11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 64 [24%] of 265 patients in the durvalumab plus platinum–etoposide group, and 88 [33%] of 266 patients in the platinum–etoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 85 (32%) in the durvalumab plus platinum–etoposide group, and 97 (36%) in the platinum–etoposide group. Treatment-related deaths occurred in 12 (5%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) patients in the durvalumab plus platinum–etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinum–etoposide group (pancytopenia and thrombocytopenia [n=1 each]). Interpretation: First-line durvalumab plus platinum–etoposide showed sustained overall survival improvement versus platinum–etoposide but the addition of tremelimumab to durvalumab plus platinum–etoposide did not significantly improve outcomes versus platinum–etoposide. These results support the use of durvalumab plus platinum–etoposide as a new standard of care for the first-line treatment of ES-SCLC. Funding: AstraZeneca.

Background: Most patients with small-cell lung cancer (SCLC) have extensive-stage disease at presentation, and prognosis remains poor. Recently, immunotherapy has demonstrated clinical activity in extensive-stage SCLC (ES-SCLC). The CASPIAN trial assessed durvalumab, with or without tremelimumab, in combination with etoposide plus either cisplatin or carboplatin (platinum–etoposide) in treatment-naive patients with ES-SCLC. Methods: This randomised, open-label, phase 3 trial was done at 209 sites across 23 countries. Eligible patients were adults with untreated ES-SCLC, with WHO performance status 0 or 1 and measurable disease as per Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were randomly assigned (in a 1:1:1 ratio) to durvalumab plus platinum–etoposide; durvalumab plus tremelimumab plus platinum–etoposide; or platinum–etoposide alone. All drugs were administered intravenously. Platinum–etoposide consisted of etoposide 80–100 mg/m2 on days 1–3 of each cycle with investigator's choice of either carboplatin area under the curve 5–6 mg/mL per min or cisplatin 75–80 mg/m2 (administered on day 1 of each cycle). Patients received up to four cycles of platinum–etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks in the immunotherapy groups and up to six cycles of platinum–etoposide every 3 weeks plus prophylactic cranial irradiation (investigator's discretion) in the platinum–etoposide group. The primary endpoint was overall survival in the intention-to-treat population. We report results for the durvalumab plus platinum–etoposide group versus the platinum–etoposide group from a planned interim analysis. Safety was assessed in all patients who received at least one dose of their assigned study treatment. This study is registered at ClinicalTrials.gov, NCT03043872, and is ongoing. Findings: Patients were enrolled between March 27, 2017, and May 29, 2018. 268 patients were allocated to the durvalumab plus platinum–etoposide group and 269 to the platinum–etoposide group. Durvalumab plus platinum–etoposide was associated with a significant improvement in overall survival, with a hazard ratio of 0·73 (95% CI 0·59–0·91; p=0·0047]); median overall survival was 13·0 months (95% CI 11·5–14·8) in the durvalumab plus platinum–etoposide group versus 10·3 months (9·3–11·2) in the platinum–etoposide group, with 34% (26·9–41·0) versus 25% (18·4–31·6) of patients alive at 18 months. Any-cause adverse events of grade 3 or 4 occurred in 163 (62%) of 265 treated patients in the durvalumab plus platinum–etoposide group and 166 (62%) of 266 in the platinum–etoposide group; adverse events leading to death occurred in 13 (5%) and 15 (6%) patients. Interpretation: First-line durvalumab plus platinum–etoposide significantly improved overall survival in patients with ES-SCLC versus a clinically relevant control group. Safety findings were consistent with the known safety profiles of all drugs received. Funding: AstraZeneca.

Introducción No existe un consenso sobre las indicaciones de mastectomía contralateral en pacientes diagnosticadas de cáncer de mama unilateral sin mutación germinal en BRCA1/2. Estudios previos han identificado algunos factores que pueden influir en la toma de la decisión dependientes del tumor, como el tamaño o histología, de la paciente, como la edad, y de la cirugía como la posibilidad de realizar una reconstrucción inmediata o la experiencia del cirujano. Métodos Estudio retrospectivo de una cohorte de 176 pacientes diagnosticadas de CM entre 2010 y 2016 a las que se les realizó cirugía mamaria. Se ha analizado la asociación de características del tumor y de la paciente con la toma de decisión de realizar mastectomía contralateral (MC) o no-MC. Asimismo, se han analizado los datos relacionados con la cirugía y la recurrencia por grupos mediante la curva de incidencia acumulada y el test de Gray. Resultados El número de MC se ha incrementado en nuestro centro. No hemos encontrado diferencias significativas en el desarrollo de complicaciones posquirúrgicas entre los 2 grupos de pacientes, pero sí en la estancia hospitalaria, siendo superior para MC. También hemos observado diferencias entre ambas cohortes en edad y tipo de tumor, siendo la MC más frecuente en aquellas pacientes más jóvenes y subtipo luminal A. Hemos hallado diferencias en la incidencia acumulada de recidiva entre ambos subgrupos (p = 0, 034). Conclusiones En nuestra cohorte la MC se realiza más frecuentemente en pacientes más jóvenes y con cáncer de mama luminal A. Introduction: There is no consensus on the indications for contralateral mastectomy (CM) in patients diagnosed with unilateral breast cancer without germline BRCA1/2 mutations. Prior studies have identified some factors that could influence decision-making. These factors include tumoural size and histological type; patient-related factors, such as age; and surgical factors such as the possibility of immediate reconstruction and the surgeon''s experience. Methods: Retrospective study of a cohort of 176 patients diagnosed with breast cancer between 2010 and 2016 who underwent breast surgery. We analysed the association between tumoural and patient-related characteristics with the decision to perform CM or not. We also analysed data related to surgery and recurrence by groups by using the cumulative incidence curve and the Gray test. Results: The number of CM has increased in our centre. We found no significant differences in the occurrence of post-surgical complications between the two patient groups but length of hospital stay was higher in CM. We also found differences between the two cohorts in age and tumoural type, with CM being more frequent in younger patients and those with luminal A subtype. Differences were found in the cumulative incidence of recurrence between subgroups (p = 0.034). Conclusions: In our cohort, CM was more frequent in younger patients and in those with luminal A breast cancer.

Nasopharyngeal carcinoma is an unusual tumour in Spain. It has differences in epidemiology, histology, clinical behaviour, treatment and prognosis from those of other head and neck neoplasms, which justifies separate analysis. It is a neoplasm with a high possibility of cure with a combined treatment if even it is diagnosed in an advanced locoregional stage (stage III or IV, without metastasis). The multidisciplinary team, bringing together all professionals who specialize in the diagnosis and treatment of these tumors make the decision to establish the best sequence of individualized diagnosis, staging and treatment for each patient. This guide gives recommendations for diagnosis, staging and treatment for nasopharyngeal carcinoma. The treatment recommendations are summarized as local disease, locally advance and recurrent and metastatic disease.

Hodgkin's lymphoma is a malignant disease with an incidence of 2.2 cases/100,000. The main goals of staging are to measure the extent of disease and associated prognostic factors. Distinct recommendations were produced for initial work-up, first-line therapy of early and advanced stage disease and treatment of relapsed or resistant patients.

Colorectal cancer is the third most common malignant neoplasm and the second cause of death by cancer in western countries. In this manuscript, the clinical guidelines of the Spanish Society of Medical Oncology (SEOM) for diagnosis and adjuvant treatment of colon cancer and rectal cancer are reported.

Colorectal cancer is the first cause of cancer diagnosis in Spain. Over half of the patients are diagnosed with or will eventually develop distant metastasis. The current manuscript aims to provide synthetic practical guidelines for the therapeutic approaches in advanced disease. Available systemic therapeutic options, and integration and sequencing of chemotherapy with surgical procedures are discussed. Extent of disease, treatment objective, tumor kras mutation status, as well as patient's functional and comorbid conditions shall be considered to properly design the most adequate therapeutic strategy.

The purpose of this article is to provide updated recommendations for the diagnosis and treatment of patients non-small-cell lung cancer (NSCLC). The staging system for lung cancer has recently been revised by the International Association for Study of Lung Cancer and patients with NSCLC shall now be staged according to the UICC system 7th edition. Recommendations for treatment were based on treatment strategies that improve overall survival. In functionally fit patients with stage I-II disease surgical resection is recommended. Four cycles of adjuvant cisplatin-based chemotherapy is recommended in patients with pathologic stage II-III. For patients with stage IIIA and non-bulky mediastinal lymph node survival was significantly improved with induction chemotherapy plus surgical resection. Patients with unresectable or bulky stage IIIA and those with stage IIIB, should be treated with platinum-based chemotherapy and thoracic radiotherapy. For patients with metastatic disease and performance status of 0 or 1, a platinum-based two-drug combination of cytotoxic drugs is recommended. Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy. For elderly patients and those with performance status of 2, a single cytotoxic drug is sufficient. Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment. Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy. The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor (EGFR) mutation; for negative or unknown EGFR mutation status, cytotoxic chemotherapy is preferred. Bevacizumab is recommended with platinum-based chemotherapy, except for patients with certain clinical characteristics. Maintenance therapy with pemetrexed or erlotinib increases survival in patients who did not progress after 4 cycles of a platinum based chemotherapy. Docetaxel, erlotinib, gefitinib, or pemetrexed is recommended as second-line therapy. Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib. Data are insufficient to recommend the routine third-line use of cytotoxic drugs.

Diffuse large B-cell non-Hodgkin's lymphoma (LDCGB) is one of the best examples of chemotherapy curable malignant diseases. This "Oncoguía SEOM" summarizes the basic directions of staging and recommended treatment options. The staging study should be thorough and includes clinical, laboratory, diagnostic imaging and nuclear medicine. Treatment depends on patient characteristics and comorbidity and on disease extension and prognostic factors. In localized cases, chemoimmunotherapy (CHOP-R) of short duration, followed by involved-field irradiation is the preferred option. In advanced stages, the association of CHOP-like chemotherapy and Rituximab has been a major breakthrough in terms of cure rate. It is important do not forget the supportive treatment in these patients.

Treatment of anaemia is a very important aspect in the management of cancer patients. In order to carry out a consensus process about the use of erythropoietic stimulating agents (ESAs) in cancer patients, the Spanish Society of Medical Oncology (SEOM) elaborated a working group which coordinated a panel of medical oncology specialists. This working group has reviewed the main issues about the use of ESAs. In addition a consensus meeting was held in Madrid on 25 April 2007. The following conclusions were made: Since ESA treatment increases the haemoglobin (Hb) level and decreases the red blood cell (RBC) transfusion requirements, ESAs should be used within the approved indications in patients undergoing chemotherapy treatment, beginning at a Hb level below 11 g/dl and maintaining it around 12 g/dl, with iron supplements if necessary. Neither increasing the ESA dose in non-responders nor the use of ESAs in the treatment of chronic cancer-related anaemia is recommended.

Fundamento Se ha descrito una importante actividad (50% de respuestas objetivas) con un pequeno numero de supervivientes en los ensayos clinicos de quimioinmunoterapia (QIT) para el melanoma diseminado. En la mayoria, la hospitalizacion era un requerimiento habitual.

The poor prognosis of non-small-cell lung cancer (NSCLC) is changing thanks to the constant development of new treatments and the introduction of target therapies, even in stage IV disease. This patient had bone metastases when he was diagnosed. Maintenance treatment, a much discussed topic nowadays, achieved a dramatic complete response.

Chemotherapy-induced emesis is one of the most frequent side effects that affect the quality of life of cancer patients undergoing chemotherapy. In recent years, clinical research has allowed us to increase our therapeutic arsenal with new drugs that have increased efficiency in the control of nausea and vomiting associated with chemo. This guide provides and update of the earlier published by our society and represents the continued commitment of SEOM to move forward and improve in the supportive care of cancer patients.

Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin's lymphoma (NHL) in the Western world. FL constitutes the most frequent indolent lymphoma, well characterized by its clinical presentation related to nodal involvement and its morphologic and biologic features. It is often managed as an incurable disease. However, several active therapeutic approaches from the "wait and watch" strategy to the allogeneic transplantation are available for management of patients with FL and clearly have changed the natural history of this disease, achieving a long-term disease-free survival. Therapeutic decision is mostly conditioned by patient's characteristics, stage, histological grade, tumor burden, and risk-predicting factors. This article try to summarizes the diagnosis and treatment of this heterogeneous group of patients.

In this issue of Clinical and Translational Oncology, the Spanish Society for Medical Oncology (SEOM) publishes a group of the Clinical Guidelines that are the result of an ambitious educational programme. The main objective of this programme was to periodically create and actualise a set of clinical guidelines mainly focused on the medical treatment for the majority of solid tumours and cancerrelated or therapy-related symptoms. Clinical guidelines have increasingly become a common part of clinical practice during the past decade. They are defi ned by the Institute of Medicine as “systematically developed statements to assist practitioner and patient decisions about appropriate health care for specifi c clinical circumstances” [1]. Appropriate care involves assessing the balance between the sum of the benefi ts and the sum of the risks [2]. There are several factors that have stimulated increased interest in the development of clinical guidelines. Among the most relevant reasons are the exponential increment of medical publications, rising healthcare costs, the use of more expensive technologies, variations in service delivery among providers even within the same city or geographic region and the aspiration of healthcare physicians to offer the best possible care to their cancer patients. In this scenario, clinical guidelines are considered as a tool for giving the patients the best care based on the most consistent scientifi c evidence. Therapy based on guidelines has been shown to lead to better clinical outcomes compared with locally adapted therapeutic strategies and this would also lead to improved quality of care for the patients. Several objectives can be assigned to clinical guidelines. The main aim is usually to improve the quality of the medical care. However, other important objectives to consider are to facilitate the decision-making process for the treating physician, to promote effi cient use of the health system resources and to set the basis for performing an evaluation of the quality of medical care. Clinical guidelines’ highest quality probably lies in the methodology for constructing them based on the comprehensive review of the literature and the most convincing evidence-based medicine available. Nowadays, there are many clinical guidelines in oncology, produced by different institutions, governments, scientifi c societies and cooperative groups. So why has SEOM launched a new group of clinical guidelines? This initiative is the result of the intent to adapt the best evidence-based knowledge in medical oncology to the specifi c scenario of the Spanish health care system and to actively cooperate with the health authorities in the homogenisation of medical oncology care among the different communities in Spain. For this purpose, the board of SEOM created a working group in 2008 with the aim of coordinating this project. The clinical guidelines working group established the methodology and the basis for building each guideline. They defi ned some common characteristics for each guideline with special emphasis on being clear and concise but complete at the same time, and the use of tables or algorithms for facilitating comprehension. It should be highlighted that the recommendations made by the clinical guidelines should be in accordance with the approvals obtained by the different therapies in Spain at the moment of writing the guideline. Regarding the authors, a fi rst panel of experts was nominated in order to write the fi rst draft of the guideline. Then, a second panel of experts also nomiD. Isla Casado SEOM Clinical Guidelines Coordinator Servicio de Oncologia Medica Hospital Clinico Universitario Lozano Blesa Zaragoza, Spain

Head and neck cancer constitutes the fifth highest cause of cancer in Spain. It is a neoplasm with a high possibility of cure if it is diagnosed in early stages, but unfortunately two thirds of the patients are diagnosed at an advanced loco-regional stage (stage III and IV, without metastasis). The multidisciplinary team, bringing together all professionals who specialize in the diagnosis and treatment of these tumors make the decision to establish the best sequence of individualized diagnosis, staging and treatment for each patient. This guide gives recommendations for diagnosis, staging and treatment for squamous cell carcinoma of the head and neck. In order to simplify the amount of information about any subsite of the head and neck area, the treatment recommendations are summarized as local disease, locally advance resectable and unresectable stages, function-preserving laryngeal treatment and recurrent and metastatic disease.

Patients with metastatic breast cancer have a wide number of treatment options, including medical, surgical, and supportive care measures. Treatment decisions are based in predictive and prognostic factors and the informed choice of the patients. SEOM has elaborated these guidelines with evidence-based recommendations for the diagnostic work-up, treatment (chemotherapy, endocrine therapy and targeted therapies) and supportive care for the management of these patients.

The incidence is increasing due to mammographic screening and an ageing population. In some countries the mortality rate has decreased especially in middleaged and younger groups because of improved treatment and possibly earlier detection. However, breast cancer is still the leading cause of cancer-related death in European women. The purpose of this work was to elaborate a Spanish Society of Medical Oncology guideline on pharmacologic interventions for early breast cancer (BC). We have compiled the latest advances in the management of this pathology either in the adjuvant and neoadjuvant setting, cytostatic and hormonal treatment, so that in a simple way could be useful to oncologist, residents and other related specialties.