Effectiveness and Safety of Pixantrone for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma in Every-Day Clinical Practice: The Italian Cohort of the PIXA Registry.

INTRODUCTION: Treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) represents a challenge for clinicians due to the lack of therapeutic options. DLBCL is not a rare disease in Italy. Pixantrone is an aza-anthracenedione, which, when compared to anthracyclines and anthracenediones, has a significantly reduced cardiotoxicity while maintaining good anti-tumor activity. However, the evidence on the use of pixantrone in the context of daily clinical practice is scarce. METHODS: We focused on the Italian patient subset of a larger European retrospective study (the PIXA Registry) to assess the efficacy and safety of pixantrone in a real-life DLBCL population. The molecular profile of the disease and its impact on drug efficacy were also assessed. RESULTS: Fifteen heavily pretreated DLBCL patients (13 males and 2 females) underwent treatment with pixantrone for a median of 2 cycles (range 1-6). Eight patients were bcl2 positive, 7 bcl6 positive, and 4 myc positive; 4 patients were diagnosed as double-hit, and 2 as triple-hit DLBCL. The overall response rate was 26.7% with a best response rate of 46.7%. Three patients had grade IV adverse events, which caused drug discontinuation. Four patients had 5 cases of grade III toxicities (1 thrombocytopenia, 1 stomatitis, and 3 neutropenia). One mild cardiac toxicity (sinus tachycardia for which no action was required) was possibly related to the study drug. CONCLUSION: Our data documented drug efficacy that is satisfactory for this high-risk subset of patients with an acceptable toxicity profile. Results indicate that pixantrone could be a significant treatment option in patients with R/R aggressive DLBCL treated in everyday clinical practice.

Italian results of the PRECONNECT study: safety and efficacy of trifluridine/tipiracil in metastatic colorectal cancer.

The international PRECONNECT Phase IIIb study demonstrated safety and efficacy of trifluridine/tipiracil in the management of patients with metastatic colorectal cancer. Post-hoc analyses in a national context are important because of the differences in disease management across countries. Post-hoc safety and efficacy analyses in the PRECONNECT Italian patient subset were conducted. Patients' quality of life was assessed from baseline to end of treatment. In Italy, 161 patients were enrolled. The median age was 64 years, with a performance status of 0-1. The most common hematological drug-related adverse events ≥grade 3 were neutropenia (41.0%) and anemia (13.7%). The median progression-free survival was reached at 3.0 months, with a disease control rate of 28.6%. The Quality of Life Questionnaire Core 30 score improved in 25.4% of the patients. Safety, efficacy and quality of life results confirmed trifluridine/tipiracil as a feasible and favorable treatment option for metastatic colorectal cancer patients.

Lay abstract PRECONNECT is an international study demonstrating the efficacy and tolerability of the drug combination trifluridine/tipiracil in adult patients with metastatic colorectal cancer treated in everyday clinical practice. For this publication, the authors conducted an analysis performed on the 161 Italian patients enrolled in this study. These kinds of analyses are important because of the differences that may arise across different countries. The most common contraindications were not dangerous to health. Furthermore, 3 months from beginning the medication, half of the patients did not show a worsening of the disease and quality of life during treatment was maintained. Clinical trial registration: NCT03306394 (ClinicalTrials.gov).

Efficacy and safety of pixantrone for the treatment of multiply relapsed or refractory aggressive non-Hodgkin B-cell lymphomas.

BACKGROUND AND OBJECTIVE: Few treatment options exist for patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) who fail first- and second-line therapies. Pixantrone is a novel aza-anthracenedione agent with reduced potential for cardiotoxicity but maintained anti-tumour activity relative to anthracyclines. The current retrospective, observational, real-life study was undertaken in 79 patients who received pixantrone monotherapy for multiply R/R aggressive B-cell NHL in Spain and Italy. RESULTS: Before pixantrone, patients had received a median of 3 prior therapies and 84.6% of them were refractory to the last regimen. Median progression-free survival (mPFS) was 2.8 months (95% confidence interval [CI] 2.1-3.6) and median overall survival (mOS) was 4.0 months (95%CI 5.6-7.9), with an objective response rate (ORR) of 29% (complete remission [CR]: 13.2%, partial remission [PR]: 15.2%). Patients receiving ≥2 cycles of pixantrone showed mPFS and mOS of 3.1 and 6.0 months, respectively, and an ORR of 36.8% (CR: 17.5%, PR: 19.3%). Overall, 63.3% of patients reported ≥1 adverse event (AE), most commonly haematological AEs. One patient developed grade 2 sinus tachycardia. CONCLUSION: Pixantrone was effective and well tolerated in a real-world population of multiply R/R patients with aggressive B-cell NHL, many of whom had very poor prognostic factors.