A prospective, real-world, multinational study of febrile neutropenia (FN) occurrence in oncology patients receiving chemotherapy with intermediate risk of FN: a MASCC Neutropenia, Infection, and Myelosuppression Study Group initiative.

PURPOSE: Limited knowledge is available on the incidence of febrile neutropenia (FN) in intermediate-risk patients and the rationale for use of granulocyte colony-stimulating factor (G-CSF) in these patients. We aimed to estimate the rate at which patients associated with intermediate risk (10-20%) of FN would develop ≥ 1 episode of FN with a commonly used chemotherapy regimen in clinical practice. METHODS: This prospective, real-world, observational, multinational, multicenter study (December 2016-October 2019) recruited patients with solid tumors or Hodgkin's/non-Hodgkin's lymphoma. Patients receiving chemotherapy with intermediate risk of FN, but not G-CSF as primary prophylaxis were included and observed for the duration of the chemotherapy (≤ 6 cycles and ≤ 30 days after the last chemotherapy administration). RESULTS: In total, 364 patients (median age, 56 years) with 1601 cycles of chemotherapy were included in the analysis. The incidence of FN was 5% in cycle 1, 3% in cycles 2-3, and 1% in cycles 4-6. The rate of patients with ≥ 1 episode of FN was 9%, and 59% of FN events were reported during cycle 1. The rate of grade 4 neutropenia in cycle 1 was 11%, and 15% of patients experienced ≥ 1 episode of grade 4 neutropenia. CONCLUSIONS: Overall, the incidence of FN was low, with a high incidence in cycle 1 and a decrease in the subsequent cycles. These results provide the real FN risk for common chemotherapy regimens in patients generally excluded from clinical trials. Prophylactic G-CSF in intermediate-risk patients could be considered as per clinician's judgement.

High risk of thrombosis in patients with advanced lung cancer harboring rearrangements in ROS1.

INTRODUCTION: Based on the high incidence of thromboembolic events (TEs) observed in lung adenocarcinomas with ALK translocations and taking into account the biological proximity of ROS1 and ALK, we conducted a retrospective analysis of patients with advanced lung carcinoma carrying rearrangements in ROS1 from 23 centres in Spain and one centre in Portugal. METHODS: The main objective of the study was to analyse the incidence of TE in this population, looking for predictive risk factors, and its impact on overall survival. RESULTS: A total of 58 patients were included. The incidence of TEs throughout the disease was 46.6% (n = 27) with a median follow-up of 19 months (range: 1-78 months) and a median overall survival of 52 months in the total population and 50 months for the patients presenting TEs, with a hazards ratio of 1.12 (95% confidence interval: 0.47-2.65) p = 0.78. The majority of the events were venous (n = 24; 89%) and occurred in the ambulatory setting (n = 18; 67%). Almost half of the patients (n = 13; 48%) presented the TE in the peri-diagnostic period. CONCLUSIONS: The high incidence of thrombosis, especially during the cancer diagnosis process, requires special attention from a clinician. Despite the limitations of such a small descriptive study, its results are in accordance with previously reported data. It would be important to design prospective studies of antithrombotic prophylaxis in this population because of their possible impact in reducing the risk of TEs.

Intravenous 5-Fluorouracil in Patients With Advanced Squamous Cell Carcinoma: A Retrospective Study.

OBJECTIVES: In the EXTREME trial, a combination of cisplatin or carboplatin plus 5-fluorouracil (5-FU) and cetuximab was superior to cisplatin/carboplatin plus 5-FU for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). With the aim of improving fluoropyrimidine-related tolerance without decreasing its efficacy, the safety and efficacy of carboplatin plus the oral fluoropyrimidine tegafur and cetuximab were investigated. METHODS: A retrospective analysis of 104 patients with recurrent or metastatic HNSCC was conducted. Patients were treated with carboplatin (area under the curve: 5 mg/mL/min) on day 1, oral tegafur (250 mg/m2 twice daily) for 21 consecutive days, and cetuximab (400 mg/m2 as an initial 2-hour intravenous infusion, then 250 mg/m2 as a 1-hour weekly infusion for 3 weeks) for ≤6 cycles. Patients who responded to the therapy then received weekly cetuximab maintenance therapy. RESULTS: Treatment was well tolerated with a high level of compliance (relative dose intensity: 96%, 88%, and 81% for carboplatin, tegafur, and cetuximab, respectively). Grade 3-4 adverse events (AEs) were observed in 38% of patients (skin reactions in 17% of patients, anemia 4%, and neutropenia 3%). Grade 1-2 AEs included skin reactions (52% of patients), hypomagnesemia (20%), asthenia (19%), and anemia (13%). No venous thrombosis related to chemotherapy perfusion was observed. Over a median follow-up of 21 months, the median overall and progression-free survival were 11 and 6 months, respectively, and the overall response rate was 35%. CONCLUSIONS: Carboplatin plus oral tegafur and cetuximab is a safe, well-tolerated first-line therapy for recurrent or metastatic HNSCC.

The biology behind PI3K inhibition in chronic lymphocytic leukaemia.

Phosphoinositide 3'-kinase (PI3K) is a key component of both chronic active and tonic B-cell receptor-signalling pathways. As such, PI3K inhibitors have emerged as promising therapeutic agents for diverse lymphoid malignancies, particularly chronic lymphocytic leukaemia. Multiple in vitro experiments and clinical trials have shown efficacy of these agents across all prognostic subgroups with a favourable toxicity profile. Moreover, in vitro studies suggest that combinations with monoclonal antibodies and/or other immune strategies could enhance the effect of PI3K inhibition.