LONSURF

What it is

LONSURF is a film-coated tablet containing trifluridine and tipiracil hydrochloride, available in two strengths: 15 mg trifluridine with tipiracil hydrochloride 7.065 mg (equivalent to tipiracil 6.14 mg), and 20 mg trifluridine with tipiracil hydrochloride 9.420 mg (equivalent to tipiracil 8.19 mg). LONSURF comprises an antineoplastic thymidine-based nucleoside analogue, trifluridine, and the thymidine phosphorylase inhibitor, tipiracil hydrochloride, at a molar ratio 1:0.5.

Approved indications

— Adult patients with metastatic colorectal cancer who have been previously treated with, or are not considered candidates for fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents. — Adult patients with metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.

Dosing overview

The recommended starting dose of LONSURF in adults is 35 mg/m² /dose (based on the trifluridine component) administered orally twice daily on Days 1 to 5 and Days 8 to 12 of each 28-day cycle as long as benefit is observed or until unacceptable toxicity occurs. The maximum dose per dose is 80 mg. For patients with severe renal impairment, a starting dose of 20 mg/m² twice daily is recommended. Administration is not recommended in patients with end stage renal disease. Administration is not recommended in patients with baseline moderate or severe hepatic impairment (total bilirubin > 1.5 x ULN).

Key safety warnings

LONSURF caused severe and life-threatening myelosuppression (Grade 3–4) consisting of anaemia (12.1%), neutropenia (34.1%), thrombocytopenia (3.7%) and febrile neutropenia (3%). Two patients (0.2%) died due to neutropenic infection/sepsis and four other patients (0.5%) died due to septic shock. For cycle 1, consider clinical review and full blood count on day 15 and then as clinically indicated; thereafter obtain complete blood counts prior to each cycle of LONSURF and more frequently as clinically indicated, and withhold LONSURF for severe myelosuppression and resume at the next lower dosage. LONSURF caused an increase in the incidence of gastrointestinal toxicities including nausea, vomiting, and diarrhoea, and patients with these symptoms should be carefully monitored with appropriate measures such as antiemetic, anti-diarrhoeal, and/or fluid/electrolyte replacement therapy administered as clinically indicated. LONSURF contains lactose and patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Contraindications

LONSURF is contraindicated in patients with a history of previous hypersensitivity to tipiracil, trifluridine or any of the excipient ingredients.

PBS listing

LONSURF was recommended by PBAC in July 2018 for metastatic colorectal cancer (patients previously treated or not suitable for current available therapies) with Authority Required (streamlined) listing. In November 2019, PBAC recommended it for metastatic gastric cancer (metastatic, previously treated) with Authority Required (streamlined) listing.

Regulatory history

LONSURF was first listed on the ARTG on 23 May 2017 with two registered variants: LONSURF 15/6.14 (ARTG 273239) and LONSURF 20/8.19 (ARTG 273238). The PBAC recommended LONSURF for treatment of metastatic colorectal cancer in November 2017. In July 2018, the PBAC recommended a streamlined Authority Required listing with reduced price and a Risk Share Agreement. In November 2019, the PBAC recommended it for metastatic gastric cancer with a streamlined Authority Required listing at the proposed price.