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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.

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.

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 2.8months (95% confidence interval [CI] 2.1-3.6) and median overall survival (mOS) was 4.0months (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 6.0months, 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.

BACKGROUND: The objective of this study was to evaluate the effectiveness and safety of pixantrone as a rescue treatment for NHL patients in a real world population in Spain and Italy as data on the use of this drug in everyday clinical practice is still scarce. METHODS: The study included patients aged ≥18 years with histologically proven relapsed or refractory B-cell aNHL who were treated according to pixantrone's product information. Primary endpoint was progression-free survival (PFS). Secondary endpoints included the proportion of patients with complete response (CR), partial response (PR), overall response rate (ORR), overall survival (OS), as well as safety. RESULTS: 79 patients were included in 52 centers. At diagnosis, mean age was 65 years (95% CI 62-68) and 83% had ECOG 0-1. At pixantrone treatment initiation, 82% of patients presented Ann Arbor stage III-IV, and 64% an International Prognostic Index (IPI) Score ≥3; 85% were refractory and 15% relapsed. Median number of previous therapies was 3 (range 1-5). Patients received a median of two cycles of pixantrone (range 1-6). ORR was 29% with 13.2% CR and 15.8% PR. Median PFS and OS were 2.8 months (95% CI 2.1-3.6) and 4 months (95% CI 3.6-4.4), respectively. There was a trend towards better PFS in relapsed vs refractory patients (12.5 vs 2.6 months, respectively, p=0.059). Patients who received two or more cycles of pixantrone had 38% ORR (CR 17.5%; PR 19.3%). Adverse reactions to pixantrone were reported in 63% of patients. The most frequent toxicities were hematological (67.1%) and gastrointestinal (12%). No febrile neutropenia or clinical cardiotoxicity was reported. CONCLUSIONS: Although a high percentage of patients with very poor prognostic factors was included in this study (82% Ann Harbor III-IV, 63% IPI ≥3, and 85% refractory), treatment with pixantrone appears to be effective. There was a trend to better efficacy in terms of PFS in relapsed vs refractory patients. In those patients who received ≥2 cycles, pixantrone was more effective compared to those who received less than two cycles, with ORR similar to the pivotal study. Pixantrone treatment resulted active and well tolerated in real world clinical practice. Keywords: Refractory non-Hodgkin lymphoma; Relapsed non-Hodgkin lymphoma; Salvage therapy; pixantrone. Disclosures Sancho: Roche: Speakers Bureau; Janssen: Speakers Bureau; Kern Pharma: Speakers Bureau; Roche: Honoraria; Gilead: Honoraria; Celgene: Speakers Bureau; Mundipharma: Speakers Bureau; Sanofi: Speakers Bureau; Servier: Speakers Bureau; Bristol-Myers: Membership on an entity's Board of Directors or advisory committees; Celltrion: Membership on an entity's Board of Directors or advisory committees. Grasso Cicala:Servier: Employment. Spione:Servier: Employment. Zinzani:PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Honoraria, Speakers Bureau; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra Zeneca: Speakers Bureau.

Aim: RECOURSE trial has shown a benefit for trifluridine/tipiracil (also known as TAS-102) over placebo in chemorefractory metastatic colorectal cancer (mCRC) patients. We evaluated efficacy and safety of patients treated with trifluridine/tipiracil in compassionate use. Patients & methods: RETROTAS is a retrospective study designed to evaluate efficacy and safety of trifluridine/tipiracil in mCRC patients previously exposed or not a candidate to all available drugs. Results: A total of 85 mCRC patients were included. Our data showed that 37.6% of patients achieved disease control. Median progression-free survival was 2.3 months; at 16 months follow-up, median overall survival was 9.2 months. Conclusion: This real-life experience confirms the safety and efficacy of trifluridine/tipiracil, resulting as a valid option in chemorefractory mCRC treatment scenario.