A phase I, open-label, single-dose study to evaluate the effect of hepatic impairment on the pharmacokinetics and safety of futibatinib.

Futibatinib is a covalently binding FGFR1-4 inhibitor that received US Food and Drug Administration approval for the treatment of patients with previously treated, advanced intrahepatic cholangiocarcinoma harboring FGFR2 gene fusions/rearrangements. This phase I trial evaluated the pharmacokinetics (PKs), safety, and tolerability of futibatinib in subjects with impaired hepatic function and matched healthy volunteers. Twenty-two subjects with hepatic impairment (8 mild [Child-Pugh 5-6], 8 moderate [7-9], and 6 severe [10-15]) and 16 matched healthy control subjects received a single oral dose of futibatinib 20 mg.

Effects of prior therapies on outcomes with trifluridine/tipiracil in patients with metastatic gastric/gastroesophageal junction cancer in a randomized phase III trial (TAGS).

Background: In the phase III TAGS trial, trifluridine/tipiracil showed survival benefit versus placebo in patients with metastatic gastric/gastroesophageal junction cancer and ≥ 2 prior chemotherapies. This post hoc exploratory analysis assessed the impact of prior therapy type on outcomes.

Methods: Based on prior treatment, patients in TAGS (N = 507) were categorized into overlapping subgroups: ramucirumab ± other agents (n = 169), no ramucirumab (n = 338), paclitaxel but no ramucirumab (n = 136), ramucirumab + paclitaxel sequentially or in combination (n = 154), neither paclitaxel nor ramucirumab (n = 202), irinotecan (n = 281), and no irinotecan (n = 226).

Efficacy and safety of trifluridine/tipiracil in older and younger patients with metastatic gastric or gastroesophageal junction cancer: subgroup analysis of a randomized phase 3 study (TAGS).

Background: Trifluridine and tipiracil (FTD/TPI) demonstrated survival benefit vs placebo and manageable safety in previously treated patients with metastatic gastric/gastroesophageal junction cancer (mGC/GEJC) in the randomized, placebo-controlled, phase 3 TAGS study. This subgroup analysis of TAGS examined efficacy/safety outcomes by age.

Methods: In TAGS, patients with mGC/GEJC and ≥ 2 prior therapies were randomized (2:1) to receive FTD/TPI 35 mg/m or placebo, plus best supportive care.

Trifluridine/tipiracil in patients with metastatic gastroesophageal junction cancer: a subgroup analysis from the phase 3 TAGS study.

Background: Patients with advanced gastroesophageal junction cancer (GEJC) have poor survival outcomes, and GEJC-specific data from trials evaluating agents in gastric cancers (GCs) as a whole are lacking. Trifluridine/tipiracil (FTD/TPI) was approved for previously treated metastatic GC or GEJC (mGC/mGEJC) based on results of the phase 3 TAGS trial. Subgroup analyses by primary tumor type (GC or GEJC) in TAGS are reported here.

A phase 2 trial of trifluridine/tipiracil plus nivolumab in patients with heavily pretreated microsatellite-stable metastatic colorectal cancer.

Background: Microsatellite-stable (MSS) colorectal cancer (CRC) tends to be poorly immunogenic, with limited treatment options. In MSS CRC xenograft models, trifluridine/tipiracil (FTD/TPI) plus programed death 1 inhibitors resulted in synergistic antitumor activity and increased tumor immunogenicity. This phase 2 study evaluated FTD/TPI plus nivolumab in patients with MSS metastatic CRC.

Long-term safety and efficacy of lomitapide in patients with homozygous familial hypercholesterolemia: Five-year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER).

Background: Lomitapide is a lipid-lowering agent indicated as adjunct therapy for homozygous familial hypercholesterolemia (HoFH) in adults.

Objective: The Lomitapide Observational Worldwide Evaluation Registry is an international, observational registry assessing long-term safety, tolerability, and effectiveness of lomitapide.

Methods: This analysis examines 5-year data from the registry up to February 28, 2019.

A randomized, phase 2 study of deoxyuridine triphosphatase inhibitor, TAS-114, in combination with S-1 versus S-1 alone in patients with advanced non-small-cell lung cancer.

Introduction TAS-114 is a potent inhibitor of deoxyuridine triphosphatase, which is a gatekeeper protein preventing uracil and 5-fluorouracil (5-FU) misincorporation into DNA. TAS-114 has been suggested to enhance the antitumor activity of 5-FU. This randomized, phase 2 study investigated TAS-114 plus S-1 (TAS-114/S-1) vs.

Phase I Study of Trifluridine/Tipiracil Plus Irinotecan and Bevacizumab in Advanced Gastrointestinal Tumors.

Purpose: This two-part phase Ib trial determined the maximum tolerated dose (MTD) of the combination of trifluridine/tipiracil (FTD/TPI) and irinotecan in patients with advanced gastrointestinal tumors, and evaluated the safety, pharmacokinetics, and antitumor activity of the FTD/TPI, irinotecan, and bevacizumab triplet combination in previously treated metastatic colorectal cancer (mCRC).

Patients And Methods: Dose escalation (3+3 design) in advanced gastrointestinal tumors was followed by expansion in mCRC. During dose escalation, patients received FTD/TPI (20-35 mg/m twice daily; days 1-5 of a 14-day cycle) and irinotecan (120-180 mg/m; day 1).

Efficacy and Safety of Trifluridine/Tipiracil Treatment in Patients With Metastatic Gastric Cancer Who Had Undergone Gastrectomy: Subgroup Analyses of a Randomized Clinical Trial.

Importance: Trifluridine/tipiracil (FTD/TPI) treatment has shown clinical benefit in patients with pretreated metastatic gastric cancer or gastroesophageal junction cancer (mGC/GEJC). Patients who have undergone gastrectomy constitute a significant proportion of patients with mGC/GEJC.

Objective: To assess the efficacy and safety of FTD/TPI among patients with previously treated mGC/GEJC who had or had not undergone gastrectomy.

Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Trifluridine/tipiracil showed activity and was well tolerated in a phase 2 study of pretreated patients with advanced gastric cancer done in Japan. We investigated whether the treatment was efficacious compared with placebo in a global population.

Methods: TAGS was a randomised, double-blind, placebo-controlled, phase 3 trial done in 110 academic hospitals in 17 countries.

Safety of trifluridine/tipiracil in an open-label expanded-access program in elderly and younger patients with metastatic colorectal cancer.

Purpose: Trifluridine/tipiracil (FTD/TPI; TAS-102, Lonsurf®), a novel form of chemotherapy for metastatic colorectal cancer (mCRC), has shown clinical benefit in the global, phase III RECOURSE trial, regardless of patient age. Here, we report the safety and tolerability profile of FTD/TPI from an expanded-access program (EAP) in the US patients with mCRC whose disease has progressed on the standard therapies.

Methods: A total of 549 patients (≥ 18 years) with histologically confirmed mCRC following two or more regimens of standard therapy and an Eastern Cooperative Oncology Group performance status of 0 or 1 participated in this open-label EAP.

The subgroups of the phase III RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo with best supportive care in patients with metastatic colorectal cancer.

Background: In the phase III RECOURSE trial, trifluridine/tipiracil (TAS-102) extended overall survival (OS) and progression-free survival (PFS) with an acceptable toxicity profile in patients with metastatic colorectal cancer refractory or intolerant to standard therapies. The present analysis investigated the efficacy and safety of trifluridine/tipiracil in RECOURSE subgroups.

Methods: Primary and key secondary end-points were evaluated using a Cox proportional hazards model in prespecified subgroups, including geographical subregion (United States of America [USA], European Union [EU], Japan), age (<65 years, ≥65 years) and v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homologue (KRAS) status (wild type, mutant).

Proxies of quality of life in metastatic colorectal cancer: analyses in the RECOURSE trial.

Background: In the pivotal phase III, randomised, double-blind, placebo-controlled RECOURSE study, treatment with trifluridine/tipiracil was well tolerated and associated with prolonged progression-free and overall survival in patients with metastatic colorectal cancer (mCRC). There was no formal analysis of quality of life (QoL) in RECOURSE. The aim of the present analysis was to assess proxies of QoL during the RECOURSE treatment period, in terms of adverse events (AEs) likely to affect QoL and Eastern Cooperative Oncology Group performance status (ECOG PS).

Phase III HEAT Study Adding Lyso-Thermosensitive Liposomal Doxorubicin to Radiofrequency Ablation in Patients with Unresectable Hepatocellular Carcinoma Lesions.

Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of doxorubicin contained within a heat-sensitive liposome. When heated to ≥40°C, LTLD locally releases a high concentration of doxorubicin. We aimed to determine whether adding LTLD improves the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) lesions with a maximum diameter () of 3 to 7 cm.

A phase 2 randomized study of TAS-102 versus topotecan or amrubicin in patients requiring second-line chemotherapy for small cell lung cancer refractory or sensitive to frontline platinum-based chemotherapy.

Objectives: TAS-102 is an oral combination treatment comprised of an antimetabolite, trifluridine, a thymidine-based nucleoside analog, and tipiracil hydrochloride, at a molar ratio of 1:0.5. This antimetabolite has demonstrated efficacy in clinical trials, including a global phase 3 trial in metastatic colorectal cancer.

LOWER, a registry of lomitapide-treated patients with homozygous familial hypercholesterolemia: Rationale and design.

Background: Lomitapide is an orally active selective inhibitor of microsomal triglyceride transfer protein approved as adjunctive therapy for homozygous familial hypercholesterolemia (HoFH). The Lomitapide Observational Worldwide Evaluation Registry (LOWER) is a global, long-term, prospective, observational treatment registry established as a regulatory requirement.

Objectives: LOWER will evaluate the long-term safety and effectiveness of lomitapide in clinical practice.

Does Better Specimen Orientation and a Simplified Grading System Promote More Reliable Histologic Interpretation of Serrated Colon Polyps in the Community Practice Setting? Results of a Nationwide Study.

Introduction: Colonoscopic surveillance guidelines for serrated polyps (SPs) are predicated upon the histologic characteristics of the index polyp. However, discrimination between SP subtypes [hyperplastic polyps vs. sessile serrated adenoma/polyps (SSA/P)] is often unreliable.

Randomized trial of TAS-102 for refractory metastatic colorectal cancer.

Background: Early clinical trials conducted primarily in Japan have shown that TAS-102, an oral agent that combines trifluridine and tipiracil hydrochloride, was effective in the treatment of refractory colorectal cancer. We conducted a phase 3 trial to further assess the efficacy and safety of TAS-102 in a global population of such patients.

Methods: In this double-blind study, we randomly assigned 800 patients, in a 2:1 ratio, to receive TAS-102 or placebo.