PURPOSE: Venous thromboembolism (VTE) is a leading cause of death among patients with cancer. The Khorana score was developed for assessing the risk of VTE in outpatients with cancer receiving chemotherapy, but its accuracy in identifying patients at high risk has been questioned. The aim of this study was to develop and validate a clinical-genetic score that improves the assessment of VTE risk in oncology outpatients within 6 months of diagnosis. METHODS: The new score was developed using the data of 364 outpatients belonging to the Spanish ONCOTHROMB 12-01 population. In this cohort, clinical data associated with the risk of VTE were collected at the time of diagnosis, including the Khorana score. These patients were also genotyped for the 51 genetic variants known to be associated with VTE. Multivariate logistic regression was performed to determine the weight of each genetic and clinical variable in relation to VTE risk, allowing a clinical-genetic risk score (the ONCOTHROMB score) to be developed. The Khorana and the ONCOTHROMB scores were then compared via the area under the receiver operating characteristic curve (AUC), calibration, and the number of patients needed to treat. The new score was then validated in a study of 263 patients in the Vienna Cancer and Thrombosis Study population. RESULTS: Nine genetic variants, tumor site, TNM stage, and a body mass index of > 25 kg/m² were found to be associated with VTE and were used to build the ONCOTHROMB score, which better predicted the overall risk of VTE than did the Khorana score (AUC, 0.781 v 0.580; P < .001). Similar AUC results were recorded in the validation study the Vienna Cancer and Thrombosis Study cohort involving patients with the same type of tumor (AUC for the ONCOTHROMB score v the Khorana score: 0.686 v 0.577; P < .001) and with all type of tumors (AUC for the ONCOTHROMB score v the Khorana score: 0.720 v 0.561; P < .0001). CONCLUSION: The ONCOTHROMB score for VTE risk in outpatients with cancer, which takes into account both clinical and genetic variables, better identifies patients who might benefit from primary thromboprophylaxis than does the Khorana score.

The Spanish Society of Medical Oncology (SEOM) last published clinical guidelines on venous thromboembolism (VTE) and cancer in 2019, with a partial update in 2020. In this new update to the guidelines, SEOM seeks to incorporate recent evidence, based on a critical review of the literature, to provide practical current recommendations for the prophylactic and therapeutic management of VTE in patients with cancer. Special clinical situations whose management and/or choice of currently recommended therapeutic options (low-molecular-weight heparins [LMWHs] or direct-acting oral anticoagulants [DOACs]) is controversial are included.

Purpose: Patients with gastric cancer, biliary tract cancer (BTC), and pancreatic ductal adenocarcinoma (PDAC) have poor survival outcomes and limited second- or later-line treatment options. Certain drugs targeting vascular endothelial growth factor (VEGF) or programmed cell death protein 1 (PD-1) signaling pathways are currently used in these cancers in specific circumstances; however, there remains a need for novel treatment combinations. LEAP-005 is a multicohort, open-label, phase II study that evaluated lenvatinib (multitargeted inhibitor of tyrosine kinases, including VEGF) plus pembrolizumab (anti–PD-1 monoclonal antibody) in select previously treated solid tumors. Patients and Methods: Participants with previously treated, advanced gastric cancer, BTC, and PDAC were enrolled in cohorts C, F, and G of LEAP-005, respectively, and received lenvatinib 20 mg/day orally plus pembrolizumab 200 mg i.v. every 3 weeks. Primary endpoints were objective response rate (ORR) and safety. Results: Of 99, 102, and 103 total participants enrolled in cohorts C, F, and G, respectively, median times from first dose of study treatment to data cutoff (February 6, 2023) were 23.7, 24.2, and 19.5 months. ORRs (95% confidence interval) by blinded independent central review were 15.2% (8.7%–23.8%) in cohort C, 17.6% (10.8%–26.4%) in cohort F, and 7.8% (3.4%–14.7%) in cohort G. Grade 3 to 5 treatment-related adverse events occurred in 54.5% of participants in cohort C, and grade 3 to 4 (no grade 5) occurred in 60.8% and 59.2% of participants in cohorts F and G, respectively. Conclusions: Lenvatinib plus pembrolizumab demonstrated modest antitumor activity and a manageable safety profile in previously treated, advanced gastric cancer, BTC, and PDAC. Significance: In the phase II LEAP-005 study, lenvatinib plus pembrolizumab showed modest antitumor activity and a manageable safety profile in participants with previously treated gastrointestinal-related cancers. Exploratory analyses in participants with BTC indicated higher ORRs in participants with targetable alterations versus those without.

Apixaban and rivaroxaban are two direct-acting oral anticoagulants (DOACs) recommended for thromboprophylaxis in cancer patients treated with chemotherapy in an ambulatory setting. We aimed to assess the cost-utility of thromboprophylaxis with apixaban and rivaroxaban vs no thromboprophylaxis in ambulatory cancer patients starting chemotherapy with an intermediate-to-high risk of venous thromboembolism (VTE), Khorana score ≥ 2 points. A cost-effectiveness analysis was performed from the perspective of Spain´s National Health System (NHS) using an analytical decision model in the short term (180 days) and a Markov model in the long term (5 years). Transition probabilities were obtained from randomized, double-blind, placebo-controlled clinical trials of apixaban and rivaroxaban in adult ambulatory patients with cancer at risk for VTE, treated with chemotherapy (AVERT and CASSINI trials). The costs (€2021) were taken from Spanish sources. The utilities of the model were obtained through the EQ-5D questionnaire. Deterministic (base case) and probabilistic (second-order Monte Carlo simulation) analyses were conducted. In the probabilistic sensitivity analysis, apixaban generated a cost per patient of €1,082 ± 187 with a 95% confidence intervals (CI) of €713;1,442, while no prophylaxis produced a cost per patient of €1,146 ± 218 with a 95% CI of €700; 1491, with a saving of €64 per patient and a gain of 0.008 QALYs. Likewise, rivaroxaban provided a cost per patient of €993 ± 133 with a 95% CI of €748; 1,310, while no prophylaxis produced a cost per patient of €872 ± 152 with a 95% CI of €602; 1,250, with an additional expense of €121 per patient and a gain of 0.008 QALYs. In thromboprophylaxis of cancer patients, the use of apixaban and rivaroxaban generated similar cost compared to non-prophylaxis, without the difference found being statistically significant, with a clinically insignificant QALY gain.