LONSURF® (trifluridine and tipiracil) tablets, for a new FDA-approved indication

• Katrina Williams
• February 28, 2019
• News

On February 23, 2019, the U.S. Food and Drug Administration approved LONSURF® (trifluridine and tipiracil) tablets for metastatic gastric or gastroesophageal junction (GEJ) 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. ¹LONSURF is also indicated for the treatment of adult patients with metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

LONSURF is a combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor for adult patients.²  Refer to the tables below for the appropriate ICD-10 diagnosis codes as well as how LONSURF is supplied and its aligned NDC codes.

^NDC has been “zero‑filled” to ensure creation of an 11‑digit code that meets HIPAA standards. The zero‑fill location is indicated in bold. HIPAA=Health Insurance Portability and Accountability Act.³

The recommended starting dose of LONSURF is 35 mg/m² up to a maximum of 80 mg per dose (based on the trifluridine component) orally twice daily with food on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until disease progression or unacceptable toxicity.  Round dose to the nearest 5 mg increment.²

The clinical efficacy and safety of LONSURF was evaluated in TAGS (NCT02500043), an international, randomized, double-blind, placebo-controlled study in patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma who were previously treated with at least 2 prior chemotherapy regimens for advanced disease. A total of 507 patients were randomized to LONSURF (N=337) or placebo (N=170). The median overall survival with LONSURF was 5.7 months (95% CI: 4.8, 6.2) vs. 3.6 months (95% CI: 3.1, 4.1) with placebo (HR = 0.69 [95% CI: 0.56, 0.85]: P=0.0006. ² 

Additional Important Safety Information

WARNINGS AND PRECAUTIONS²

Severe Myelosuppression:

LONSURF caused severe and life threatening myelosuppression (Grade 3 4) consisting of neutropenia (38%), anemia (18%),  thrombocytopenia (5%), and febrile neutropenia (3%). Two patients (0.2%) died due to neutropenic infection. A total of 12% of LONSURF treated patients received granulocyte colony stimulating factors. Obtain complete blood counts prior to and on day 15 of each cycle of LONSURF and more frequently as clinically indicated. Withhold LONSURF for febrile neutropenia, absolute neutrophil count less than 500/mm3, or platelets less than 50,000/mm3. Upon recovery, resume LONSURF at a reduced dose as clinically indicated.

Embryo Fetal Toxicity:

LONSURF can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 6 months after the final dose.

USE IN SPECIFIC POPULATIONS

Lactation:

It is not known whether LONSURF or its metabolites are present in human milk. There are no data to assess the effects of LONSURF or its metabolites on the breast fed infant or the effects on milk production. Because of the potential for serious adverse reactions in breast fed infants, advise women not to breastfeed during treatment with LONSURF and for 1 day following the final dose.

Male Contraception:

Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use condoms during treatment with LONSURF and for at least 3 months after the final dose.

Geriatric Use:

Patients 65 years of age or over who received LONSURF had a higher incidence of the following compared to patients younger than 65 years: Grade 3 or 4 neutropenia (48% vs 30%), Grade 3 anemia (22% vs 16%), and Grade 3 or 4 thrombocytopenia (7% vs 4%).

Hepatic Impairment:

Do not initiate LONSURF in patients with baseline moderate or severe (total bilirubin greater than 1.5 times ULN and any AST) hepatic impairment. Patients with severe hepatic impairment (total bilirubin greater than 3 times ULN and any AST) were not studied. No adjustment to the starting dose of LONSURF is recommended for patients with mild hepatic impairment.

Renal Impairment:

No adjustment to the starting dosage of LONSURF is recommended in patients with mild or moderate renal impairment (CLcr of 30 to 89 mL/min). Patients with severe renal impairment (CLcr < 30 mL/min) were not studied.

ADVERSE REACTIONS

Most Common Adverse Drug Reactions in Patients Treated With LONSURF (≥5%):

The most common adverse drug reactions in LONSURF treated patients vs placebo treated patients with mCRC, respectively, were asthenia/fatigue (52% vs 35%), nausea (48% vs 24%), decreased appetite (39% vs 29%), diarrhea (32% vs 12%), vomiting (28% vs 14%), infections (27% vs 16%), abdominal pain (21% vs 18%), pyrexia (19% vs 14%), stomatitis (8% vs 6%), dysgeusia (7% vs 2%), and alopecia (7% vs 1%). In metastatic gastric cancer or gastroesophageal junction (GEJ), the most common adverse drug reactions, respectively were, nausea (37% vs 32%), decreased appetite (34% vs 31%), vomiting (25% vs 20%), infections (23% vs 16%) and diarrhea (23% vs 14%).

Pulmonary emboli occurred more frequently in LONSURF treated patients compared to placebo: (2% vs 0%) in mCRC and (3% vs 2%) in metastatic gastric cancer and GEJ.

Interstitial lung disease (0.2%), including fatalities, has been reported in clinical studies and clinical practice settings in Asia.

Laboratory Test Abnormalities in Patients Treated With LONSURF:

Laboratory test abnormalities in LONSURF treated patients vs placebo-treated patients with mCRC, respectively, were anemia (77% vs 33%), neutropenia (67% vs 1%), and thrombocytopenia (42% vs 8%).  In metastatic gastric cancer or GEJ, the test abnormalities, respectively, were neutropenia (66% vs 4%), anemia (63% vs 38%), and thrombocytopenia (34% vs 9%).

Please see full Prescribing Information for LONSURF (trifluridine and tipiracil) tablets athttps://www.taihooncology.com/us/prescribing-information.pdf. For more information, please visit https://www.lonsurf.com.

On behalf of Taiho Oncology, Inc.