Molecular therapies for HCC: Looking outside the box

Summary Over the past decade, sorafenib has been the only systemic agent with proven clinical efficacy for patients with unresectable hepatocellular carcinoma (HCC). Recently, lenvatinib was shown to be non-inferior to sorafenib, while regorafenib, cabozantinib, and ramucirumab were shown to be superior to placebo in patients failing sorafenib. In addition, trials of immune checkpoint inhibitors reported encouraging efficacy signals. However, apart from alpha-fetoprotein, which is used to select patients for ramucirumab, no biomarkers are available to identify patients that may respond to a specific treatment. Different synergisms have been postulated based on the potential interplay between antiangiogenic drugs and immunotherapy, with several clinical trials currently testing this hypothesis. Indeed, encouraging preliminary results of phase I studies of bevacizumab plus atezolizumab and lenvatinib plus pembrolizumab have led to the design of ongoing phase III trials, including both antiangiogenics and immune checkpoint inhibitors in the front-line setting. Other important phase II studies have tested molecular therapies directed against different novel targets, such as transforming growth factor-beta, MET (hepatocyte growth factor receptor), and fibroblast growth factor receptor 4. These studies integrated translational research with the aim of better defining the biological tumour profile and identifying tumour and blood biomarkers that select patients who may really benefit from a specific molecular therapy. Importantly, good safety profiles make these drugs suitable for future combinations. In this review, we discuss the most recent data on novel combination strategies and targets, as well as looking ahead to the future role of molecular therapies in the treatment of patients with advanced HCC

Oral anticoagulant prescribing among patients with cancer and atrial fibrillation in England, 2009–2019:OAC prescribing in AF patients with cancer

BACKGROUND: Anticoagulation of patients with atrial fibrillation (AF) and cancer is challenging because of their high risk for stroke and bleeding. Little is known of the variations of oral anticoagulant (OAC) prescribing in patients with AF with and without cancer.METHODS: Patients with first-time AF during 2009-2019 from the Clinical Practice Research Datalink were included. Cancer diagnosis was defined as a history of breast, prostate, colorectal, lung, or hematological cancer. Competing-risk analysis was used to assess the risk of OAC prescribing in patients with AF and cancer adjusted for clinical and sociodemographic factors.RESULTS: Of 177,065 patients with AF, 11.7% had cancer. Compared to patients without cancer, patients with cancer were less likely to receive OAC: prostate cancer (subhazard ratio [SHR], 0.95; 95% CI, 0.91-0.99), breast cancer (SHR, 0.93; 95% CI, 0.89-0.98), colorectal cancer (SHR, 0.93; 95% CI, 0.88-0.99), hematological cancer (SHR, 0.70; 95% CI, 0.65-0.75), and lung cancer (SHR, 0.44; 95% CI, 0.38-0.50). The cumulative incidence function (CIF) of OAC prescribing was lowest for patients with lung cancer and hematological cancer compared with patients without cancer. The difference between the CIF of OAC prescribing in patients with and without cancer becomes narrower in the most deprived areas. Elderly patients (aged ≥85 years) overall had the lowest CIF of OAC prescribing regardless of cancer status.CONCLUSIONS: In patients with AF, underprescribing of OAC is independently associated with certain cancer types. Patients with hematological and lung cancer are the least likely to receive anticoagulation therapy compared with patients without cancer. Underprescribing of OAC in cancer is linked to old age. Further studies of patients with AF and cancer are warranted to assess the net clinical benefit of anticoagulation in certain cancer types.</p