RENO Study: Clinical characteristics, treatment patterns and survival results in patients with metastatic renal cell carcinoma in Northern Spain.

BACKGROUND: The current available evidence on the management of metastatic renal cell cancer (mRCC) in real life is scarce in our environment. We present a summary of the existing real-world data and the results of an analysis describing the clinical characteristics, treatments, and health outcomes of patients with mRCC in northern Spain. METHODS: Retrospective observational study. Adult patients diagnosed with mRCC between Jan 2007 and Dec 2019 were included. Epidemiological, efficacy and toxicity data were collected. Median overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan-Meier method. RESULTS: A total of 829 patients were included (median age at diagnosis:63 years;73% men). Median follow-up was 180 months. The preponderant histology was clear cell (85%). In 50% the initial diagnosis was advanced disease. The distribution according to IMDC prognosis was good (24%), intermediate (50%) and poor (26%). The most frequent metastatic locations were lung (68.3%) and lymph node (41.0%). Most patients (95%) received a first line (1L) systemic treatment, 60% were treated with a second line (2L) of therapy and 37% received third line (3L). A VEGFR-TKIs was the most common treatment (1L: 90%, n = 507; 2L: 49%, n = 233; 3L: 54%, n = 156) followed by mTOR inhibitors (1L: 2%, n = 4; 2L: 27%, n = 126; 3L: 23%, n = 68) and immunotherapy (1L: 3.7%, n = 25; 2L: 27%, n = 126). Median OS was 24.5 months in the general population. According to IMDC prognostic groups, OS was 52.5, 25.7 and 9 months respectively. From the start of the 1L, 2L, and 3L treatment, median PFS was: 1L: 7.8 (6.8-9.0); 2L: 4.9 (4.3-5.5); 3L: 4.3 (3.8-4.8) months. No unexpected toxicity was reported. CONCLUSIONS: The Real-World Data on the management of mRCC in Northern Spain are comparable in epidemiology, efficacy, and safety to studies conducted in other areas of the world. The significant reduction in the number of patients receiving second and subsequent lines of therapy hampers the access to new therapies developed in this context.

Incidence, risk factors, and evolution of venous thromboembolic events in patients diagnosed with pancreatic carcinoma and treated with chemotherapy on an outpatient basis.

BACKGROUND: Pancreatic carcinoma is one of the tumors associated with a higher risk for thromboembolic events, with incidence rates ranging from 5% to 41% in previous retrospective series. PATIENTS AND METHODS: We conducted a retrospective study in eleven Spanish hospitals that included 666 patients diagnosed with pancreatic carcinoma (any stage) between 2008 and 2011 and treated with chemotherapy. The main objective was to evaluate the incidence of venous thromboembolic events (VTE) in this population, as well as potential risk factors for thrombosis. The impact of VTE on mortality was also assessed. RESULTS: With a median follow-up of 9.3 months, the incidence of VTE was 22.1%; 52% were diagnosed incidentally. Our study was unable to confirm the ability of the Khorana score to discriminate between patients in the intermediate or high risk category for thrombosis. The presence of VTE proved to be an independent prognostic factor associated with increased risk of death (HR 2.39, 95% CI 1.96-2.92). Symptomatic events correlated with higher mortality than asymptomatic events (HR 1.72; 95% CI, 1.21-2.45; p = 0.002), but incidental VTE, including visceral vein thrombosis (VVT), negatively affected survival compared to patients without VTE. Subjects who developed VTE within the first 3 months of diagnosis of pancreatic carcinoma had lower survival rates than those with VTE after 3 months (HR 1.92, 95% CI 1.30-2.84; p<0.001). CONCLUSIONS: Pancreatic carcinoma is associated with a high incidence of VTE, which, when present, correlates with worse survival, even when thrombosis is incidental. Early onset VTE has a particularly negative impact.

Immune checkpoint inhibitors-associated thrombosis in patients with lung cancer and melanoma: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group.

PURPOSE: Immune Checkpoint Inhibitors (ICI) can be associated with thrombotic events, both venous and arterial (VTE/AT). However, there is a paucity of information regarding patients in routine clinical practice. METHODS/PATIENTS: Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Patients with melanoma and lung cancer who initiated ICI between 01/01/2015 and 31/12/2019 were recruited. Minimum follow-up was 6 months (unless it was not possible because of death). The primary objective was to calculate the incidence of ICI-associated VTE/AT and the secondary objectives included to analyze its impact on survival and to identify predictor variables for VTE/AT. RESULTS: 665 patients with lung cancer were enrolled. The incidence of VTE/AT during follow-up was 8.4%. Median overall survival (OS) was lower in the VTE/AT group (12 months 95% CI 4.84-19.16 vs. 19 months 95% CI 16.11-21.9; p = 0.0049). Neutrophil/lymphocyte ratio (NLR) and anemia upon initiation of IT, as well as a history of thrombosis between cancer diagnosis and the start of ICI, were predictive variables for developing of VTE/AT (p < 0.05). 291 patients with melanoma were enrolled. There was a 5.8% incidence rate of VTE/AT during follow-up. Median OS was lower in the VTE/AT group (10 months 95% CI 0.0-20.27 vs. 29 months 95% CI 19.58-36.42; p = 0.034). NLR and lactate dehydrogenase (LDH) at the beginning of ICI were predictor variables for VTE/AT (p < 0.05). CONCLUSIONS: ICI increases the risk of VTE/AT in patients with lung cancer and melanoma, which impact OS.

Consensus on prevention and treatment of cancer-associated thrombosis (CAT) in controversial clinical situations with low levels of evidence.

BACKGROUND: Cancer patients suffer high risk of venous thromboembolism (VTE). Cancer-associated VTE (CAT) causes hospitalization, morbidity, delayed cancer treatment, and mortality; therefore, exceptional CAT prevention and management are imperative. METHODS: This review offers practical recommendations and treatment algorithms for eight complex, clinically relevant situations posing great uncertainty regarding management and requiring an urgent decision: VTE prophylaxis in ambulatory cancer patients with pancreatic pancreas (1) or lung cancer with molecular alterations (2); optimal management of VTE during antineoplastic treatment with antiangiogenics (3) or chemotherapy (4); protracted VTE treatment, determinants; (5) drugs used (6), and optimal VTE management in situations of high bleeding risk (7) or recurrent VTE (8). RESULTS: With the evidence available, primary thromboprophylaxis in patients with lung cancer harbouring ALK/ROS1 translocations or pancreatic cancer receiving ambulatory chemotherapy must be appraised. If antiangiogenic therapy can yield a clear benefit and the patient recovers from a grade 3 thrombotic event, it can be cautiously re-introduced in selected cases, provided that the person agrees to assume the risk after being duly informed. Anticoagulation maintenance beyond 6 months is recommended in individuals with metastatic tumours, on active treatment, or at high risk for recurrent VTE without bleeding risk. In such cases, LMWH and DOACs are safe, being mindful that the latter could entail a higher risk of bleeding; consequently, they should be used judiciously in more haemorrhagic tumours, such as gastrointestinal cancers. In cases of recurrent VTE, the presence of active cancer, infra-therapeutic dose, and anticoagulant treatment failure must be ruled out. In individuals with platelet counts of 25,000-50,000 and VTE liable to recur who need anticoagulation, full-dose LMWH and transfusion support can be contemplated to reach values of > 50,000. In CAT unlikely to recur, decreasing the LMWH dose by 25-50% is recommended. Renal impairment associated with thrombosis must be treated with LMWHs; there is no need to adjust the dose in patients with CrCl > 30; with CrCl = 15-30, dose adjustment is advised, and suspended when CrCl is < 15. CONCLUSION: We provide useful advice for complex, clinically relevant situations that clinicians treating CAT must face devoid of any unequivocal, strong, evidence-based recommendations.