Summary of Research: Adjuvant Nivolumab Plus Ipilimumab Versus Placebo for Localized Renal Cell Carcinoma After Nephrectomy (CheckMate 914): A Double-Blind, Randomized, Phase 3 Trial.

This is a summary of a research article reporting Part A of the CheckMate 914 study (NCT03138512; EudraCT 2016-004502-34). Following surgery to remove renal cell carcinoma (RCC), people with a high risk of the cancer returning received nivolumab plus ipilimumab (adjuvant therapy) or placebo to see if this risk was reduced. The results of this study showed that the risk of RCC returning or death was not changed with adjuvant nivolumab plus ipilimumab treatment compared with placebo. In addition, people treated with nivolumab plus ipilimumab had more side effects compared with people treated with placebo (89% versus 57%).

Adjuvant nivolumab plus ipilimumab versus placebo for localised renal cell carcinoma after nephrectomy (CheckMate 914): a double-blind, randomised, phase 3 trial.

BACKGROUND: Effective adjuvant therapy for patients with resected localised renal cell carcinoma represents an unmet need, with surveillance being the standard of care. We report results from part A of a phase 3, randomised trial that aimed to assess the efficacy and safety of adjuvant nivolumab plus ipilimumab versus placebo. METHODS: The double-blind, randomised, phase 3 CheckMate 914 trial enrolled patients with localised clear cell renal cell carcinoma who were at high risk of relapse after radical or partial nephrectomy between 4-12 weeks before random assignment. Part A, reported herein, was done in 145 hospitals and cancer centres across 20 countries. Patients were randomly assigned (1:1) to nivolumab (240 mg) intravenously every 2 weeks for 12 doses plus ipilimumab (1 mg/kg) intravenously every 6 weeks for four doses, or matching placebo, via an interactive response technology system. The expected treatment period was 24 weeks, and treatment could be continued until week 36, allowing for treatment delays. Randomisation was stratified by TNM stage and nephrectomy (partial vs radical). The primary endpoint was disease-free survival according to masked independent central review; safety was a secondary endpoint. Disease-free survival was analysed in all randomly assigned patients (intention-to-treat population); exposure, safety, and tolerability were analysed in all patients who received at least one dose of study drug (all-treated population). This study is registered with ClinicalTrials.gov, NCT03138512. FINDINGS: Between Aug 28, 2017, and March 16, 2021, 816 patients were randomly assigned to receive either adjuvant nivolumab plus ipilimumab (405 patients) or placebo (411 patients). 580 (71%) of 816 patients were male and 236 (29%) patients were female. With a median follow-up of 37·0 months (IQR 31·3-43·7), median disease-free survival was not reached in the nivolumab plus ipilimumab group and was 50·7 months (95% CI 48·1 to not estimable) in the placebo group (hazard ratio 0·92, 95% CI 0·71-1·19; p=0·53). The number of events required for the planned overall survival interim analysis was not reached at the time of the data cutoff, and only 61 events occurred (33 in the nivolumab plus ipilimumab group and 28 in the placebo group). 155 (38%) of 404 patients who received nivolumab plus ipilimumab and 42 (10%) of 407 patients who received placebo had grade 3-5 adverse events. All-cause adverse events of any grade led to discontinuation of nivolumab plus ipilimumab in 129 (32%) of 404 treated patients and of placebo in nine (2%) of 407 treated patients. Four deaths were attributed to treatment with nivolumab plus ipilimumab and no deaths were attributed to treatment with placebo. INTERPRETATION: Adjuvant therapy with nivolumab plus ipilimumab did not improve disease-free survival versus placebo in patients with localised renal cell carcinoma at high risk of recurrence after nephrectomy. Our study results do not support this regimen for the adjuvant treatment of renal cell carcinoma. FUNDING: Bristol Myers Squibb and Ono Pharmaceutical.

Dabrafenib plus trametinib treatment in patients with anaplastic thyroid carcinoma: an Argentinian experience.

PURPOSE: To present our real-life experience with dabrafenib and trametinib (D-T) treatment in patients with BRAF V600E-mutated ATC in Argentina. PATIENTS Y METHODS: We included five patients from four different hospitals. The median age was 70 years, and 60% were male. The performance status at diagnosis was grade 0 in 60% and grade 2 in 40% of patients. Four patients could undergo total thyroidectomy; in one of them, surgical treatment was amenable due to the indication of D-T as neoadjuvant therapy. From the total cohort, the best response to treatment was complete response in 40%, partial response in 20%, and stable disease in 20%. The median duration of response was 20 weeks, ranging from 16 to 92 weeks. All patients experienced at least one adverse event (AE). Grade ≥3 AEs were observed in two (40%) patients. They were upper gastrointestinal bleeding and subclavian vein thrombosis. The median follow-up was 20 weeks (range: 16 to 92). CONCLUSION: This report contributes to illustrate the feasibility and effectiveness of D-T treatment in five patients with loco-regionally advanced and metastatic BRAF V600E-mutated ATC in a real-life setting. A multidisciplinary approach and rapid molecular-tailored testing are essential to begin this therapeutic option.

First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial.

BACKGROUND: First-line nivolumab plus ipilimumab has shown improved overall survival in patients with advanced non-small-cell lung cancer (NSCLC). We aimed to investigate whether the addition of a limited course (two cycles) of chemotherapy to this combination would further enhance the clinical benefit. METHODS: This randomised, open-label, phase 3 trial was done at 103 hospitals in 19 countries. Eligible patients were aged 18 years or older with treatment-naive, histologically confirmed stage IV or recurrent NSCLC, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients were randomly assigned (1:1) by an interactive web response system via permuted blocks (block size of four) to nivolumab (360 mg intravenously every 3 weeks) plus ipilimumab (1 mg/kg intravenously every 6 weeks) combined with histology-based, platinum doublet chemotherapy (intravenously every 3 weeks for two cycles; experimental group), or chemotherapy alone (every 3 weeks for four cycles; control group). Randomisation was stratified by tumour histology, sex, and PD-L1 expression. The primary endpoint was overall survival in all randomly assigned patients. Safety was analysed in all treated patients. Results reported here are from a pre-planned interim analysis (when the study met its primary endpoint) and an exploratory longer-term follow-up analysis. This study is active but no longer recruiting patients, and is registered with ClinicalTrials.gov, number NCT03215706. FINDINGS: Between Aug 24, 2017, and Jan 30, 2019, 1150 patients were enrolled and 719 (62·5%) randomly assigned to nivolumab plus ipilimumab with two cycles of chemotherapy (n=361 [50%]) or four cycles of chemotherapy alone (n=358 [50%]). At the pre-planned interim analysis (median follow-up 9·7 months [IQR 6·4-12·8]), overall survival in all randomly assigned patients was significantly longer in the experimental group than in the control group (median 14·1 months [95% CI 13·2-16·2] vs 10·7 months [9·5-12·4]; hazard ratio [HR] 0·69 [96·71% CI 0·55-0·87]; p=0·00065). With 3·5 months longer median follow-up (median 13·2 months [IQR 6·4-17·0]), median overall survival was 15·6 months (95% CI 13·9-20·0) in the experimental group versus 10·9 months (9·5-12·6) in the control group (HR 0·66 [95% CI 0·55-0·80]). The most common grade 3-4 treatment-related adverse events were neutropenia (in 24 [7%] patients in the experimental group vs 32 [9%] in the control group), anaemia (21 [6%] vs 50 [14%]), diarrhoea (14 [4%] vs two [1%]), increased lipase (22 [6%] vs three [1%]), and asthenia (tjree [1%] vs eight [2%]). Serious treatment-related adverse events of any grade occurred in 106 (30%) patients in the experimental group and 62 (18%) in the control group. Seven (2%) deaths in the experimental group (acute kidney failure, diarrhoea, hepatotoxicity, hepatitis, pneumonitis, sepsis with acute renal insufficiency, and thrombocytopenia; one patient each) and six (2%) deaths in the control group (anaemia, febrile neutropenia, pancytopenia, pulmonary sepsis, respiratory failure, and sepsis; one patient each) were treatment related. INTERPRETATION: Nivolumab plus ipilimumab with two cycles of chemotherapy provided a significant improvement in overall survival versus chemotherapy alone and had a favourable risk-benefit profile. These data support this regimen as a new first-line treatment option for patients with advanced NSCLC. FUNDING: Bristol Myers Squibb.

Recomendaciones sobre el manejo del cáncer de páncreas tipo adenocarcinoma en Latinoamérica: Reunión del Consenso del Simposio Latinoamericano de Gastroenterología Oncológica (SLAGO) y de la Asociación Ibero Latinoamericana de Terapia Radiante (ALATRO), Viña del Mar, Chile 2015 / Recommendations for the management of pancreatic cancer type adenocarcinoma: A consensus statement reached during the 2015 Latin American Symposium on Gastroenterological Oncology

Pancreatic cancer is a malignancy of great impact in developed countries and is having an increasing impact in Latin America. Incidence and mortality rates are similar for this cancer. This is an important reason to offer to the patients the best treatments available. During the Latin American Symposium of Gastroenterology Oncology (SLAGO) held in Viña del Mar, Chile, in April 2015, a multidisciplinary group of specialists in the field met to discuss about this disease. The main conclusions of this meeting, where practitioners from most of Latin American countries participated, are listed in this consensus that seek to serve as a guide for better decision making for patients with pancreatic cancer in Latin America.

[Recommendations for the management of pancreatic cancer type adenocarcinoma: A consensus statement reached during the 2015 Latin American Symposium on Gastroenterological Oncology]. / Recomendaciones sobre el manejo del cáncer de páncreas tipo adenocarcinoma en Latinoamérica: Reunión del Consenso del Simposio Latinoamericano de Gastroenterología Oncológica (SLAGO) y de la Asociación Ibero Latinoamericana de Terapia Radiante (ALATRO), Viña del Mar, Chile 2015.

Pancreatic cancer is a malignancy of great impact in developed countries and is having an increasing impact in Latin America. Incidence and mortality rates are similar for this cancer. This is an important reason to offer to the patients the best treatments available. During the Latin American Symposium of Gastroenterology Oncology (SLAGO) held in Viña del Mar, Chile, in April 2015, a multidisciplinary group of specialists in the field met to discuss about this disease. The main conclusions of this meeting, where practitioners from most of Latin American countries participated, are listed in this consensus that seek to serve as a guide for better decision making for patients with pancreatic cancer in Latin America.