
Efficacy & Safety
LONSURF:
- Extended overall survival2
- Maintained or improved ECOG performance status3
- Demonstrated safety profile4
Efficacy
Help extend survival with LONSURF
In the initial RECOURSE survival analysis, LONSURF — studied under TAS-102 — provided a statistically significant reduction in risk of mortality (32%)2
- mOS (95% CI): 7.1 months (6.5-7.8) vs 5.3 months (4.6-6.0) (HR=0.68 [95% CI: 0.58-0.81]; P<0.001)*
- Number (%) of deaths was 364 (68) for LONSURF and 210 (79) for placebo†
In the follow-up survival analysis, LONSURF maintained a 2-month benefit in median OS vs placebo3
- The follow-up survival analysis was conducted 9 months after the initial RECOURSE analysis
†Prespecified study endpoint.
Follow-up survival analysis: OS in patients with refractory mCRC3

Percent of patients surviving at 6 and 12 months4*

89% of the planned dose was received by patients in the LONSURF group vs 94% in the placebo group. The planned dose reflects the total targeted dose while patients were receiving treatment.4
Significantly prolonged progression‑free survival2,4,5

†Prespecified study endpoint.
Give patients the potential to maintain performance status with LONSURF
- 180 patients with ECOG performance status of 0 maintained their performance status
- 152 patients with ECOG performance status of 1 maintained their performance status
- 8 patients with ECOG performance status of 1 improved their performance status to 0
Results were based on the ECOG performance status scale. Grade 0 is defined as fully active and able to carry on all predisease performance without restriction. Grade 1 is defined as restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light housework, office work.7
42%
of patients in the LONSURF arm went on to receive subsequent therapy at the end of the trial4
– Approximately 16% of these patients received a regimen containing regorafenib5
Adverse Events
WARNINGS AND PRECAUTIONS
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 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 with LONSURF.
LONSURF has a demonstrated safety profile4
(n=533*), %
(n=265*), %
- *Percentage based on number of patients with post-baseline samples, which may be less than 533 (LONSURF) or 265 (placebo).
- †No Grade 4 definition for anemia in National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
(n=533), %
(n=265), %
appetite
- *No Grade 4 definition for nausea, abdominal pain, or fatigue in NCI CTCAE for Adverse Events, version 4.03.
(n=533), %
(n=265), %
syndrome
neutropenia
- Standard safety monitoring and grading were performed using NCI CTCAE for Adverse Events, version 4.03.
- In the RECOURSE study, 3.6% of patients discontinued LONSURF due to an AE and 13.7% required a dose reduction2
- -The most common AEs leading to a dose reduction were neutropenia, anemia, febrile neutropenia, fatigue, and diarrhea
- In the RECOURSE study, 9.4% of patients in the LONSURF group received granulocyte‑colony stimulating factor (G‑CSF)2
Study Design
RECOURSE: Refractory Colorectal Cancer Study (Study 1)2,5
An international, double‑blind, randomized, placebo‑controlled phase 3 clinical trial
Inclusion criteria:
- ≥18 years of age4
- Confirmed adenocarcinoma of the colon or rectum4
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 12
-
Received at least 2 prior regimens of standard chemotherapy and were refractory to or were failing all of the following within 3 months2,4:
- Fluoropyrimidine, irinotecan and oxaliplatin
- Anti‑VEGF biological therapy
- Anti‑EGFR therapy (if RAS wild type) - Disease progression based on imaging during or within 3 months of the last administration of each of the standard chemotherapies5


Patient Demographics4

- *Race was self-reported.
- †Eastern Cooperative Oncology Group (ECOG) performance status is scored on a scale of 0 to 5, with 0 indicating no symptoms, 1 indicating mild symptoms, and higher numbers indicating increasing degrees of disability.
All patients received prior treatment with fluoropyrimidine‑, oxaliplatin‑, and irinotecan‑based chemotherapy. All but one patient received bevacizumab, and all but two patients with KRAS wild‑type tumors received panitumumab or cetuximab.2
Clinical Guidelines

The National Comprehensive Cancer Network® (NCCN®) recommends trifluridine and tipiracil (LONSURF) as a potential 3rd‑line or subsequent-line treatment option in both KRAS‑mutant and wild‑type mCRC patients. See below for potential treatment algorithms.1
Kras Mutant Patients
Example Treatment Algorithm
1st-LINE
FOLFOX
+
bevacizumab
2nd-LINE
FOLFIRI
+
bevacizumab
3rd-LINE
Trifluridine
and
tipiracil
4th-LINE
Other
treatment
options
Kras Wild-Type Patients
Example Treatment Algorithm
1st-LINE
FOLFIRI
+
cetuximab
2nd-LINE
FOLFOX
+
bevacizumab
3rd-LINE
Trifluridine
and
tipiracil
4th-LINE
Other
treatment
options
1st-LINE
FOLFIRI
+
bevacizumab
2nd-LINE
FOLFOX
+
bevacizumab
3rd-LINE
Irinotecan
+
cetuximab
4th-LINE
Trifluridine
and
tipiracil
NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
For additional mCRC treatment algorithms please view the following NCCN Guidelines.
Download PDFIn the RECOURSE international clinical trial:
of the trial4
treatment regimen4
Category 2A = based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate
References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.2.2018 and the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer V.1.2018. © National Comprehensive Cancer Network, Inc 2018. All rights reserved. Accessed April 27, 2018. To view the most recent and complete version of the guidelines, go online to NCCN.org. 2. LONSURF [Prescribing Information]. Princeton, NJ: Taiho Oncology, Inc.; 03/2017 3. Van Cutsem E, Mayer RJ, Laurent S, et al; for the RECOURSE Study Group. 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. Eur J Cancer. 2018;90:63-72. 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. Data on file. Taiho Oncology, Inc., Princeton, NJ. 6. Van Cutsem E, Falcone A, Garcia-Carbonero R, et al.; Proxies of quality of life in metastatic colorectal cancer: analyses in the RECOURSE trial. ESMO Open. 2017;2(5):e000261. 7. Oken MM, Creech RH, Tormey DC, et al.; Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.
WARNINGS AND PRECAUTIONS
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 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 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 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 (26% vs 12%), and Grade 3 or 4 thrombocytopenia (9% vs 2%).
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. Do not initiate LONSURF in patients with baseline moderate or severe (total bilirubin greater than 1.5 times ULN and any AST) hepatic impairment.
Renal Impairment: In Study 1, patients with moderate renal impairment (CLcr=30 to 59 mL/min, n=47) had a higher incidence (difference of at least 5%) of ≥Grade 3 adverse events, serious adverse events, and dose delays and reductions compared to patients with normal renal function (CLcr ≥90 mL/min, n=306) or patients with mild renal impairment (CLcr=60 to 89 mL/min, n=178).
Patients with moderate renal impairment may require dose modifications for increased toxicity. Patients with severe renal impairment 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 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%).
The most commonly reported infections which occurred more frequently in LONSURF‑treated patients were nasopharyngitis (4% vs 2%) and urinary tract infections (4% vs 2%).
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 see full Prescribing Information.