INDICATION: LONSURF is indicated for the treatment of patients with metastatic colorectal cancer (mCRC) 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.
INDICATION: LONSURF is indicated for the treatment of patients with metastatic colorectal cancer (mCRC) 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.
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Efficacy & Safety

Why Lonsurf?

More options are needed for the treatment of refractory mCRC

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5-Year Survival in Stage IV Refractory Metastatic Colorectal Cancer 5-Year Survival in Stage IV Refractory Metastatic Colorectal Cancer

Based on SEER data, 20% of colorectal cancer cases diagnosed between 2004 and 2010 were metastatic at diagnosis. 5‑year survival for these patients was 12.9%.1*


“Given the current limited treatment options, mCRC patients who are refractory to standard therapy would benefit from the availability of additional treatment options. LONSURF represents such an option in this area of high unmet medical need.”2


Data source: Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute.
*SEER 18 areas (San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, Atlanta, San Jose-Monterey, Los Angeles, Alaska Native Registry, Rural Georgia, California excluding SF/SJM/LA, Kentucky, Louisiana, New Jersey, and Georgia excluding ATL/RG). Based on follow‑up of 211,799 patients into 2011.1

About LONSURF

LONSURF: The first and only oral oncolytic combination tablet for your patients with refractory mCRC3

LONSURF® (trifluridine and tipiracil) tablets combine Trifluridine and Tipiracil for metastatic colorectal cancer treatment

LONSURF® (trifluridine and tipiracil) tablets are indicated for the treatment of patients with metastatic colorectal cancer (mCRC) 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.3

The efficacy and safety profile of LONSURF (studied under TAS-102) in RECOURSE, an international, randomized, double‑blind, placebo-controlled phase 3 trial involving 800 patients with previously‑treated mCRC.3,4 All patients had KRAS wild‑type or mutated tumors.3

In the trial, randomized patients received at least 2 prior regimens of standard chemotherapy and were refractory to or were failing all of the therapies mentioned above within 3 months.3,4 Disease progression was based on imaging during or within 3 months of the last administration of each of the standard chemotherapies.2

Patient Considerations

Consider LONSURF as a balanced option for appropriate patients

LONSURF was studied under TAS-102 in the RECOURSE trial3,4

  • Patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, ranging from 27 to 82 years of age

The appropriate patient for LONSURF

  • Has been previously treated with fluoropyrimidine‑, oxaliplatin‑, and irinotecan‑based chemotherapy, an anti‑VEGF biological therapy, and if RAS wild type, an anti‑EGFR therapy1
  • Has an ECOG performance status of 0 or 11

RECOURSE was an international, randomized, double-blind, placebo-controlled phase 3 trial.* All patients were ≥18 years of age, had ECOG performance status of 0 or 1, absence of brain metastasis, and absence of ascites requiring drainage in the past four weeks and had received at least 2 prior regimens of standard chemotherapy with: fluoropyrimidine, irinotecan, and oxaliplatin; an anti-VEGF biological therapy; and, if RAS wild type, an anti-EGFR therapy. The primary efficacy endpoint was overall survival (OS).2,3,4

Patients were randomized 2:1 to receive either LONSURF 35 mg/m2 (n=534) or placebo (n=266) twice daily after meals for 5 days a week with 2 days rest for 2 weeks, followed by a 14-day rest, repeated every 4 weeks plus best supportive care.3

All patients were followed for survival at scheduled 8-week intervals with computed tomography (CT) scans until 12 months after the first dose of study medication from the last patient randomized. After the end of treatment, all patients were followed for survival at scheduled 8-week time intervals until death.2

*Treatment arms were LONSURF plus best supportive care vs placebo plus best supportive care.3

Mechanism of Action

An oral oncolytic combination tablet that interferes with the DNA of tumor cells* to inhibit proliferation3,4,5

LONSURF mechanism of action3,4,5-7

  • Uses a dual approach to inhibit rapid degradation of trifluridine and subsequently tumor growth
  • Demonstrated anti‑tumor activity against KRAS wild‑type and mutated human colorectal cancer xenografts in mice

Learn about the components of LONSURF, and how they work together:

View a detailed explanation
View a detailed explanation

LONSURF® (trifluridine and tipiracil) tablets consist of a thymidine‑based nucleoside analog, trifluridine, and the thymidine phosphorylase inhibitor, tipiracil, at a molar ratio 1:0.5 (weight ratio, 1:0.471). Inclusion of tipiracil increases trifluridine exposure by inhibiting its metabolism by thymidine phosphorylase.

Following uptake into cancer cells, trifluridine, in its triphosphate form (FTD‑TP), is incorporated into the DNA, interferes with DNA function, and inhibits cell proliferation. No enzyme has been identified for the dephosphorylation of FTD‑TP, which may explain its incorporation into DNA.

Trifluridine/tipiracil demonstrated anti‑tumor activity against KRAS wild‑type and mutant human colorectal cancer xenografts in mice.3

References: 1. National Cancer Institute. SEER cancer statistics review: 1975‑2011. http://seer.cancer.gov/csr/1975_2011/results_merged/sect_06_colon_rectum.pdf. Accessed May 7, 2015. 2. Data on file. Taiho Oncology, Inc., Princeton, NJ. 3. LONSURF [Prescribing Information]. Princeton, NJ: Taiho Oncology, Inc.; 03/2017. 4. Mayer RJ, Van Cutsem E, Falcone A, et al; for the RECOURSE Study Group. Randomized trial of TAS‑102 for refractory metastatic colorectal cancer. N Engl J Med. 2015;372(20):1909-1919. 5. Matsuoka K, Iimori M, Niimi S, et al. Trifluridine induces p53‑dependent sustained G2 phase arrest with its massive misincorporation into DNA and few DNA strand breaks. Mol Cancer Ther. 2015;14(4):1004-1013. 6. Uboha N, Hochster HS. TAS-102: a novel antimetabolite for the 21st century. Future Oncol. 2016;12(2):153-163. 7. Suzuki N, Nakagawa F, Matsuoka K, Takechi T. Effect of a novel oral chemotherapeutic agent containing a combination of trifluridine, tipiracil and the novel triple angiokinase inhibitor nintedanib, on human colorectal cancer xenografts. Oncol Rep. 2016;36(3):31‍23-31‍30.

Important Safety Information +

WARNINGS AND PRECAUTIONS

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 (46% vs 32%), 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.