Consolidation nivolumab and ipilimumab versus observation in limited-disease small-cell lung cancer after chemo-radiotherapy - results from the randomised phase II ETOP/IFCT 4-12 STIMULI trial.

BACKGROUND: Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall survival (OS) of only 25% to 33%. PATIENTS AND METHODS: STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab [1 mg/kg, every three weeks (Q3W)] plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint. RESULTS: Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months [95% confidence interval (CI) 7.0-not estimable (NE)] versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR) = 1.02 (0.66-1.58), two-sided P = 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR = 0.95 (0.59-1.52), P = 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade ≥3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively. CONCLUSIONS: The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.

A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial.

BACKGROUND: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. PATIENTS AND METHODS: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). RESULTS: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. CONCLUSIONS: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.

Management of platinum-resistant ovarian cancer with the combination of pemetrexed and gemcitabine.

INTRODUCTION: Platinum resistant ovarian cancer is a current challenge in Oncology. Current approved therapies offer no more of a 20% of response. New therapeutic options are urgently needed. PATIENTS AND METHODS: Patients were treated with the combination of Pemetrexed 500 mg/m(2) d1 and Gemcitabine 1000 mg/m(2) d1,8 in a 21 days basis. RESULTS: 10 platinum-resistant ovarian cancer patients were treated under compassionate use. Mean previous chemotherapy lines were 3.3. Mean administered cycles were 4. Mean CA 125 decrease was on average of 47%, with one patient experiencing a 95% decrease in her CA 125 level. 1 patient had a complete clinical remission, and 2, had partial radiological responses. Mean Progression free survival was 16.5 weeks, and Overall Survival was 21.2 weeks. Treatment was well tolerated. CONCLUSIONS: Deemd to the observed activity, the combination of Pemetrexed and Gemcitabine deserves deeper investigation in platinum-resistant ovarian cancer patients.

Circulating tumor cells in breast cancer: methodology and clinical repercussions.

Breast cancer is the most common type of cancer among women, and clinicians have long recognized its heterogeneity. Its detection and treatment in early stages allow for reduction of mortality. Despite the advances and new strategies for combining surgical, radiotherapy, and chemotherapy options, however, the percentage of patients developing metastases and advanced stages remains high. Even though serum tumor markers have been used for the early diagnosis of metastases, their systematic determination has not had an effect on survival. Methods that are more reliable are needed to detect metastases earlier than with the common clinical methods and thus start treatment before overt relapse. Early indicators of response or resistance to treatment are also an issue in clinical practice. Imaging techniques are time consuming, and it is difficult to detect changes that indicate response limited to therapy, and approaches to defining changes in tumor mass are time and resource consuming. In contrast, detection of circulating tumor cells (CTC) could be a useful tool in early detection of relapse and response to systemic chemotherapy. Extremely sensitive techniques are available that are easily applied to peripheral blood samples, which might provide enormous research possibilities in this area.

SEOM clinical guidelines for the treatment of follicular non-Hodgkin's lymphoma.

Follicular non-Hodgkin's lymphoma (FL) is a nodal B lymphoid malignancy that originates from the germinal center of a lymph node. FL is the second most frequent lymphoma subtype. The course of the disease is usually characterised by a typically indolent clinical course, with a median survival rate of 8-10 years, although most patients relapse after treatment. Diagnosis should always be based on a surgical specimen like an excisional node lymph biopsy. The first-line treatment of FL will depend of extension disease, tumour burden, patient symptoms, performance status and also patient decision. The addition of rituximab to conventional chemotherapy has improved ORR, PFS and OS. As first line in patients that need treatment, a combination of chemotherapy with rituximab induction followed by 2 years of rituximab maintenance is the best option. High-dose chemotherapy with autologous stem-cell transplantation in first line has not shown improvement and is not recommended as first-line therapy. Before any treatment decision in relapsed patients, a repeat biopsy is mandatory to rule out a transformation into large cell aggressive lymphoma. Standard treatment is controversial, depends on the efficacy of prior treatment, duration of the time-to-relapse, patient's age and histological findings at relapse.

SEOM clinical guidelines for the treatment of Hodgkin's lymphoma.

Hodgkin lymphoma (HL) is an uncommon B cell lymphoid malignancy representing approximately 10-15 % of all lymphomas. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte-predominant HL. An accurate assessment of the stage of disease and prognostic factors that identify patients at low or high risk for recurrence are used to optimize therapy. Patients with early stage disease are treated with combined modality strategies using abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. Brentuximab vedotin should be considered for patients who fail HDCT with ASCT.

[Prevalence of hepatitis C virus infection in patients with non-Hodgkin's lymphoma]. / Prevalencia de infección por el virus de la hepatitis C en pacientes con linfomas no hodgkinianos.

BACKGROUND: To know the prevalence of HCV infection in patients diagnosed with B-NHL in our area. PATIENTS AND METHOD: A group of patients diagnosed with B-NHL between 1998-99 were carefully reviewed (serological tests, HCV RNA, laboratory studies, toxicity, response to treatment and evolution) in a transversal study. RESULTS: Overall 9/77 (11.68%) of patients tested positive for HCV. Of the 9 patients HCV(+) showed abnormal elevated trans aminases in opposition with 10.3% of patients that tested seronegative. CONCLUSION: Compared with normal individuals, we have seen a higher prevalence of HCV in our B-NHL patients. It may be possible that HCV play a role in that lymphoma's pathogenesis.

SEOM clinical guidelines for the treatment of Hodgkin’s lymphoma

Hodgkin lymphoma (HL) is an uncommon B cell lymphoid malignancy representing approximately 10-15 % of all lymphomas. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte-predominant HL. An accurate assessment of the stage of disease and prognostic factors that identify patients at low or high risk for recurrence are used to optimize therapy. Patients with early stage disease are treated with combined modality strategies using abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. Brentuximab vedotin should be considered for patients who fail HDCT with ASCT (AU)

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SEOM clinical guidelines for the treatment of follicular non-Hodgkin’s lymphoma

Follicular non-Hodgkin's lymphoma (FL) is a nodal B lymphoid malignancy that originates from the germinal center of a lymph node. FL is the second most frequent lymphoma subtype. The course of the disease is usually characterised by a typically indolent clinical course, with a median survival rate of 8-10 years, although most patients relapse after treatment. Diagnosis should always be based on a surgical specimen like an excisional node lymph biopsy. The first-line treatment of FL will depend of extension disease, tumour burden, patient symptoms, performance status and also patient decision. The addition of rituximab to conventional chemotherapy has improved ORR, PFS and OS. As first line in patients that need treatment, a combination of chemotherapy with rituximab induction followed by 2 years of rituximab maintenance is the best option. High-dose chemotherapy with autologous stem-cell transplantation in first line has not shown improvement and is not recommended as first-line therapy. Before any treatment decision in relapsed patients, a repeat biopsy is mandatory to rule out a transformation into large cell aggressive lymphoma. Standard treatment is controversial, depends on the efficacy of prior treatment, duration of the time-to-relapse, patient’s age and histological findings at relapse (AU)

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[Locally advanced non-small cell lung cancer]. / Cáncer de pulmón no microcítico localmente avanzado.

The objective of the treatment in stages III A and III B without pleural effusion should be both locoregional and distant disease control. We known that at least 80% of the patients had micrometastatic disease at the time of diagnosis, so that a treatment that is only local would be condemned to failure from the time it is suggested. Many clinical questions continue to exist and each step achieved is followed by a new diagnostic or therapeutic dilemma and is thus a fertile field for clinical research.

SEOM clinical guidelines for the treatment of Hodgkin's lymphoma

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 (AU)

SEOM clinical guidelines for the treatment of follicular non-Hodgkin's lymphoma

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 (AU)

SEOM clinical guidelines for the treatment of diffuse large B-cell lymphoma

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 (AU)

Ocular relapse of primary brain lymphoma in immunocompetent patient, treated with intrathecal rituximab

Primary brain lymphoma is a rare variant of extranodal non-Hodgkin's B-cell lymphoma. In >90% of cases, this is diffuse large B-cell lymphoma with CD20 expression and is confined to the brain, meninges, spinal cord, and eyes. It accounts for fewer than 7% of primary brain tumors. Its incidence has been rising in recent years in immunocompetent patients in their fifth and sixth decades. The rate of relapse after initial therapy based on high-dose methotrexate and/or total brain irradiation is high. There is no consensus for treating relapse, which ranges from retreatment with high doses of methotrexate, polychemotherapy, high doses of chemotherapy backed up by autologous stem-cell transplant to intrathecal chemotherapy, with widely differing results. Given the lack of consensus and poor results, new therapy options have appeared, including immunotherapy with rituximab. At a systemic level, alongside chemotherapy, its results are very modest and limited due to the low concentration it reaches in cerebrospinal fluid (CSF). However, its intrathecal and intraventricular use, though only isolated cases have been reported, has provided promising results (AU)

Management of platinum-resistant ovarian cancer with the combination of pemetrexed and gemcitabine

INTRODUCTION: Platinum resistant ovarian cancer is a current challenge in Oncology. Current approved therapies offer no more of a 20% of response. New therapeutic options are urgently needed. PATIENTS AND METHODS: Patients were treated with the combination of Pemetrexed 500 mg/m(2) d1 and Gemcitabine 1000 mg/m(2) d1,8 in a 21 days basis. RESULTS: 10 platinum-resistant ovarian cancer patients were treated under compassionate use. Mean previous chemotherapy lines were 3.3. Mean administered cycles were 4. Mean CA 125 decrease was on average of 47%, with one patient experiencing a 95% decrease in her CA 125 level. 1 patient had a complete clinical remission, and 2, had partial radiological responses. Mean Progression free survival was 16.5 weeks, and Overall Survival was 21.2 weeks. Treatment was well tolerated. CONCLUSIONS: Deemd to the observed activity, the combination of Pemetrexed and Gemcitabine deserves deeper investigation in platinum-resistant ovarian cancer patients (AU)

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