U.S. Food and Drug Administration approved LONSURF® (trifluridine and tipiracil) tablets
On September 22, 2015, the U.S. Food and Drug Administration approved LONSURF® (trifluridine and tipiracil) tablets. LONSURF is a combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor, indicated for the treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.1
Select Important Safety Information
Severe Myelosuppression: In Study 1, LONSURF caused severe and life-threatening myelosuppression (Grade 3-4) consisting of anemia (18%), neutropenia (38%), thrombocytopenia (5%), and febrile neutropenia (3.8%). One patient (0.2%) died due to neutropenic infection. In Study 1, 9.4% 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, Grade 4 neutropenia, or platelets less than 50,000/mm3. Upon recovery, resume LONSURF at a reduced dose.
| Trade Name | Description | NDC^ | WAC Price |
| LONSURF | 15mg [15 mg trifluridine/6.14 mg tipiracil],
20 count/per bottle |
64842-1025-01 | $2,736.93 |
| LONSURF | 15mg [15 mg trifluridine/6.14 mg tipiracil],
40 count/per bottle |
64842-1025-02 | $5,473.86 |
| LONSURF | 15mg [15 mg trifluridine/6.14 mg tipiracil],
60 count/per bottle |
64842-1025-03 | $8,210.79 |
| LONSURF | 20mg [20 mg trifluridine /8.19 mg tipiracil],
20 count/per bottle |
64842-1020-01 | $3,649.24 |
| LONSURF | 20mg [20 mg trifluridine /8.19 mg tipiracil],
40 count/per bottle |
64842-1020-02 | $7,298.48 |
| LONSURF | 20mg [20 mg trifluridine /8.19 mg tipiracil],
60 count/per bottle |
64842-1020-03 | $10,947.72 |
^Note that the product’s NDC code has been “zero-filled” to ensure creation of an 11-digit code that meets CMS standards. The zero-fill location is indicated in bold.2
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 within one hour of completion of morning and evening meals 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. Do not take additional doses to make up for missed or held doses.1
The clinical efficacy and safety of LONSURF were evaluated in an international, randomized, double- blind, placebo-controlled Phase III study (RECOURSE) in 800 patients whose disease had progressed after at least 2 lines of standard chemotherapy for mCRC. This trial met the primary efficacy endpoint of statistically significant improvement in overall survival versus placebo. The median overall survival with LONSURF was 7.1 months (95% CI: 6.5, 7.8) vs 5.3 months (95% CI: 4.6, 6.0) with placebo (HR = 0.68 [95% CI:0.58-0.81]: P< 0.001).1
Additional Important Safety Information
WARNINGS AND PRECAUTIONS
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 with LONSURF.
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 breastfed infant or the effects on milk production. Because of the potential for serious adverse reactions in breastfeeding infants, advise women not to breastfeed during treatment with LONSURF and for one day following the final dose.
Male Contraception: 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: Grade 3 or 4 neutropenia and thrombocytopenia and Grade 3 anemia occurred more commonly in patients 65 years old or older who received LONSURF.
Renal Impairment: Patients with moderate renal impairment may require dose modifications for increased toxicity. No patients with severe renal impairment were enrolled in Study 1.
Hepatic Impairment: Patients with moderate or severe hepatic impairment were not enrolled in Study 1.
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 refractory 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%), abdominal pain (21% vs 18%), pyrexia (19% vs 14%), stomatitis (8% vs 6%), dysgeusia (7% vs 2%), and alopecia (7% vs 1%).
Additional Important Adverse Drug Reactions: The following occurred more frequently in LONSURF- treated patients compared to placebo: infections (27% vs 15%), and pulmonary emboli (2% vs 0%).
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 refractory mCRC, respectively, were: anemia (77% vs 33%), neutropenia (67% vs 1%), and thrombocytopenia (42% vs 8%).
Please click here for the full Prescribing Information for LONSURF (trifluridine and tipiracil) tablets.
If you require any additional information or have specific questions regarding this correspondence, please contact your Taiho Oncology Director of Market Access.
