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A balanced choice for today and tomorrow

Metastatic Colorectal Cancer

FTD/TPI (LONSURF) is recommended by the National Comprehensive Cancer Network® (NCCN®) as a third‑line or subsequent treatment option for mCRC1,2

FTD/TPI = trifluridine/tipiracil
Trifluridine/tipiracil is a treatment option for patients who have progressed through all available regimens.

Metastatic
Colorectal Cancer

FTD/TPI (LONSURF) is recommended by the National Comprehensive Cancer Network® (NCCN®) as a third‑line or subsequent treatment option for mCRC1,2

FTD/TPI = trifluridine/tipiracil
Trifluridine/tipiracil is a treatment option for patients who have progressed through all available regimens.

3rd-LINE TREATMENT

The treatment decision at 3rd-line is an important one

Less than 1/3 of mCRC patients treated at 3rd-line (3L) go on to 4th-line (4L) therapy3

Image showing that 29% of patients with previously treated mCRC moved from 3rd-line to 4th-line treatment

STUDY DESIGN

The estimate of mCRC patients moving from 3L to 4L is projected for 2021 and is based on an analysis conducted by US-based consulting firm Tessellon, using SEER data and Kantar Health’s 2018 US Treatment Architecture report for Colorectal Cancer. The Kantar survey consisted of 59 physicians actively treating CRC (collectively treating 2,741 CRC patients monthly).3,4

SEER: The Surveillance, Epidemiology, and End Results program of the National Cancer Institute

Metastatic GEJ/Gastric Cancer
Why LONSURF?

Efficacy

For patients with previously treated mCRC, help extend survival with LONSURF3,5,6

LONSURF® (FTD/TPI) tablets was studied in the RECOURSE trial5,7

LONSURF was studied in 800 patients with previously treated mCRC in the RECOURSE (Refractory Colorectal Cancer Study) trial, an international, randomized, double-blind, placebo-controlled phase 3 trial.5,7

Patients had received at least 2 prior regimens of standard chemotherapy and were refractory to or were failing all of the following within 3 months3,5,6

  • Fluoropyrimidine, irinotecan and oxaliplatin
  • Anti-VEGF biological therapy
  • Anti-EGFR therapy (if RAS wild type)

In the final survival analysis, LONSURF maintained a 2‑month benefit in mOS vs placebo

The final survival analysis was conducted 9 months after the initial RECOURSE analysis

Final survival analysis: OS in patients with previously treated mCRC5,6

Reduction in risk of Previously Treated metastatic colorectal cancer mortality with LONSURF (TAS-102) Reduction in risk of Previously Treated metastatic colorectal cancer mortality with LONSURF (TAS-102)

OS was defined as the time (in months) from randomization until death.

mOS=median OS.

aKaplan-Meier estimates.

Preserve the potential for more active treatment

42% of patients in the LONSURF arm went on to receive subsequent therapy at the end of the trial7
Approximately 16% of these patients received a regimen containing regorafenib3

Help prolong progression-free survival3,5,7

Secondary endpoint: Reduction in risk of progression or death in patients with previously treated mCRC

Reduction in risk of progression or death in patients with previously treated metastatic colorectal cancer with LONSURF Reduction in risk of progression or death in patients with previously treated metastatic colorectal cancer with LONSURF

PFS was defined as the time (in months) from randomization to the first radiologic confirmation of disease progression or death from any cause.

mPFS=median PFS.

aKaplan-Meier estimates.

bPrespecified study endpoint.

Preserve the potential for more active treatment

42% of patients in the LONSURF arm went on to receive subsequent therapy at the end of the trial7
Approximately 16% of these patients received a regimen containing regorafenib3

Give patients the potential to maintain performance status7

LONSURF tablets provided a statistically significant reduction in risk of deterioration to ECOG performance status >2 (34%)*

Median time to deterioration of ECOG PS to ≥2, based on a post-hoc analysis

Reduction in risk of deterioration of ECOG in patients with previously treated metastatic colorectal cancer with LONSURF Reduction in risk of deterioration of ECOG in patients with previously treated metastatic colorectal cancer with LONSURF

PS=performance status.

*Time to worsening of PS was prespecified in the statistical analysis plan before the data were unblinded.

ECOG Performance Status8

Results were based on the ECOG performance status scale.

  • Grade 0 = fully active and able to carry on all pre-disease performance without restriction
  • Grade 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light housework, office work
  • Grade 2 = ambulatory and capable of all self care, but unable to carry out any work activities; up and about >50% of waking hours
  • Grade 3 = capable of only limited self care and confined to a bed or chair >50% of waking hours
  • Grade 4 = completely disabled and cannot carry on any self care and totally confined to a bed or chair

Preserve the potential for more active treatment

42% of patients in the LONSURF arm went on to receive subsequent therapy at the end of the trial7
Approximately 16% of these patients received a regimen containing regorafenib3
Overall Survival

In the final survival analysis, LONSURF maintained a 2‑month benefit in mOS vs placebo

The final survival analysis was conducted 9 months after the initial RECOURSE analysis

Final survival analysis: OS in patients with previously treated mCRC5,6

Reduction in risk of Previously Treated metastatic colorectal cancer mortality with LONSURF (TAS-102) Reduction in risk of Previously Treated metastatic colorectal cancer mortality with LONSURF (TAS-102)

OS was defined as the time (in months) from randomization until death.

mOS=median OS.

aKaplan-Meier estimates.

Preserve the potential for more active treatment

42% of patients in the LONSURF arm went on to receive subsequent therapy at the end of the trial7
Approximately 16% of these patients received a regimen containing regorafenib3
Progression-free Survival

Help prolong progression-free survival3,5,7

Secondary endpoint: Reduction in risk of progression or death in patients with previously treated mCRC

Reduction in risk of progression or death in patients with previously treated metastatic colorectal cancer with LONSURF Reduction in risk of progression or death in patients with previously treated metastatic colorectal cancer with LONSURF

PFS was defined as the time (in months) from randomization to the first radiologic confirmation of disease progression or death from any cause.

mPFS=median PFS.

aKaplan-Meier estimates.

bPrespecified study endpoint.

Preserve the potential for more active treatment

42% of patients in the LONSURF arm went on to receive subsequent therapy at the end of the trial7
Approximately 16% of these patients received a regimen containing regorafenib3
ECOG Performance Status

Give patients the potential to maintain performance status7

LONSURF tablets provided a statistically significant reduction in risk of deterioration to ECOG performance status >2 (34%)*

Median time to deterioration of ECOG PS to ≥2, based on a post-hoc analysis

Reduction in risk of deterioration of ECOG in patients with previously treated metastatic colorectal cancer with LONSURF Reduction in risk of deterioration of ECOG in patients with previously treated metastatic colorectal cancer with LONSURF

PS=performance status.

*Time to worsening of PS was prespecified in the statistical analysis plan before the data were unblinded.

ECOG Performance Status8

Results were based on the ECOG performance status scale.

  • Grade 0 = fully active and able to carry on all pre-disease performance without restriction
  • Grade 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light housework, office work
  • Grade 2 = ambulatory and capable of all self care, but unable to carry out any work activities; up and about >50% of waking hours
  • Grade 3 = capable of only limited self care and confined to a bed or chair >50% of waking hours
  • Grade 4 = completely disabled and cannot carry on any self care and totally confined to a bed or chair

Preserve the potential for more active treatment

42% of patients in the LONSURF arm went on to receive subsequent therapy at the end of the trial7
Approximately 16% of these patients received a regimen containing regorafenib3

In the RECOURSE international
clinical trial:

42% of patients in the LONSURF arm went on to receive subsequent therapy at the end of the trial7
98% of patients in the LONSURF arm were refractory to or were failing on fluoropyrimidine-based therapy in a prior treatment regimen7
View the recourse
study design

Safety

Consider an option with a demonstrated safety profile

Hematologic abnormalities5,7

LONSURF + BSC
(n=533), %		 Placebo + BSC
(n=265), %
All Gra Gr 3‐4 All Gra Gr 3‐4
Anemiab 77 18 33 3
Neutropenia 67 38 1 0
Thrombocytopenia 42 5 8 <1
Febrile neutropenia 4 4 0 0
  • aWorst Grade ≥1 grade higher than baseline, with percentages based on number of patients with post-baseline samples, which may be <533 (LONSURF) OR 265 (placebo).
  • bOne Grade 4 anemia adverse reaction based on clinical criteria was reported.

What else was discovered in the RECOURSE trial?

Hand-foot syndrome was reported in 2% of patients in the LONSURF group, and 2% of patients in the placebo group. No Grade 3/4 was reported7

69% of patients who developed neutropenia (any grade) during the trial developed it during cycle 13

9.4% of patients in the LONSURF group received granulocyte-colony stimulating factor (G-CSF)6

In RECOURSE, 3.6% of patients discontinued LONSURF for an adverse reaction and 14% of patients required a dose reduction. The most common adverse reactions or laboratory abnormalities leading to dose reductions were neutropenia, anemia, febrile neutropenia, fatigue, and diarrhea5

AEs* in ≥5% of patients treated with LONSURF and occurring more commonly (>2%) than in patients taking placebo5

LONSURF + BSC
(n=533), %		 Placebo + BSC
(n=265), %
All Gr Gr 3‐4a All Gr Gr 3‐4o
General
Asthenia/fatigue 52 7 35 9
Pyrexia 19 1 14 <1
Gastrointestinal
Nausea 48 2 24 1
Diarrhea 32 3 12 <1
Vomiting 28 2 14 <1
Abdominal pain 21 2 18 4
Stomatitis 8 <1 6 0
Metabolism and nutrition
Decreased appetite 39 4 29 5
Infectionsb 27 6 16 5
Nervous system
Dysgeusia 7 0 2 0
Skin and subcutaneous tissue
Alopecia 7 0 1 0
  • aNo Grade 4 definition for nausea or fatigue in National Cancer Institute Common Terminology
  • bIncidence reflects 46 preferred terms in the Infections and Infestations system organ class.
  • *Treatment arms were LONSURF plus best supportive care (BSC) vs placebo plus BSC.

What else was discovered in the RECOURSE trial?

  • Hand-foot syndrome was reported in 2% of patients in the LONSURF group, and 2% of patients in the placebo group. No Grade 3/4 was reported7
  • 69% of patients who developed neutropenia (any grade) during the trial developed it during cycle 13
  • 9.4% of patients in the LONSURF group received granulocyte-colony stimulating factor (G-CSF)6

3.6% of patients taking LONSURF® (FTD/TPI) tablets discontinued
treatment due to an AE in the RECOURSE trial3

RECOURSE Trial
Study Design

LONSURF® (FTD/TPI) tablets was studied in the RECOURSE trial5,7

RECOURSE was an international, randomized, double-blind, placebo-controlled phase 3 clinical trial5

Inclusion criteria3,5,7:

  • Age ≥18 years
  • Confirmed adenocarcinoma of the colon or rectum
  • ECOG performance status of 0 or 1
  • Received at least 2 prior regimens of standard chemotherapy and were refractory to or were failing all of the following within 3 months
  • 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 chemotherapies

2:1 Randomization5

LONSURF + BEST SUPPORTIVE CARE (n=534)

35 mg/m2 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

Placebo + BEST SUPPORTIVE CARE (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

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.3

NCCN Clinical
Practice Guidelines
In Oncology
(NCCN Guidelines®)
for Metastatic
Colorectal Cancer

Trifluridine and
tipiracil (LONSURF)
is recommended
as a third‑line or
subsequent
treatment option
for mCRC1,2, †
Category 2A

The National Comprehensive Cancer Network® (NCCN®) recommends trifluridine and tipiracil (LONSURF®) as a potential third‑line or subsequent treatment option in both RAS mutant and wild type mCRC patients. See below for potential treatment algorithms.1,2

NCCN Guidelines for Metastatic Colon Cancer Treatment NCCN Guidelines for Metastatic Colon Cancer Treatment

These example patients are BRAF WT, pMMR/MSS, NTRK gene fusion negative, and HER2 WT.

*These treatment algorithms are examples only; other treatment options are recommended in the NCCN Guidelines®.

†Trifluridine and tipiracil is a treatment option for patients who have progressed through all available regimens.

Category 2A = based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.3.2021 and the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer V.2.2021. © National Comprehensive Cancer Network, Inc. 2021 All rights reserved.Accessed September 21, 2021. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org.

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.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer V.2.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed September 21, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.3.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed September 21, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. 3. Data on file. Taiho Oncology, Inc., Princeton, NJ. 4. CancerMPact® Treatment Architecture U.S., Kantar Health, www.cancermpact.com, Accessed December 31, 2018. 5. LONSURF [Prescribing Information]. Princeton, NJ: Taiho Oncology, Inc.; 2019. 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. 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. 8. 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.

INDICATIONS

INDICATIONS

LONSURF is indicated as a single agent or in combination with bevacizumab 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 indicated for the treatment of 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.

Indications and Important Safety Information +

INDICATIONS

LONSURF is indicated as a single agent or in combination with bevacizumab 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 indicated for the treatment of 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.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Severe Myelosuppression: In the 1114 patients who received LONSURF as a single agent, LONSURF caused severe or life‑threatening myelosuppression (Grade 3‑4) consisting of neutropenia (38%), anemia (17%), thrombocytopenia (4%) and febrile neutropenia (3%). Three patients (0.3%) died due to neutropenic infection/sepsis; four other patients (0.5%) died due to septic shock. A total of 14% of patients received granulocyte‑colony stimulating factors. In the 246 patients who received LONSURF in combination with bevacizumab, LONSURF caused severe or life-threatening myelosuppression (Grade 3‑4) consisting of neutropenia (52%), anemia (5%), thrombocytopenia (4%) and febrile neutropenia (0.4%). One patient (0.4%) died due to abdominal sepsis and two other patients (0.8%) died due to septic shock. A total of 29% of 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 severe myelosuppression and resume at the next lower dosage.

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 breastfed child or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, 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 older who received LONSURF as a single agent had a higher incidence of the following hematologic laboratory abnormalities compared to patients younger than 65 years: Grade 3 or 4 neutropenia (46% vs 32%), Grade 3 anemia (20% vs 14%), and Grade 3 or 4 thrombocytopenia (6% vs 3%). Patients 65 years of age or older who received LONSURF in combination with bevacizumab had a higher incidence of the following hematologic laboratory abnormalities compared to patients younger than 65 years: Grade 3 or 4 neutropenia (60% vs 46%) and Grade 3 or 4 thrombocytopenia (5% vs 4%).

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). Reduce the starting dose of LONSURF for patients with severe renal impairment (CLcr of 15 to 29 mL/min) to a recommended dosage of 20 mg/m2.

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

ADVERSE REACTIONS

Serious adverse reactions occurred in 25% of patients. The most frequent serious adverse reactions (≥2%) were intestinal obstruction (2.8%), and COVID-19 (2%). Fatal adverse reactions occurred in 1.2% of patients who received LONSURF in combination with bevacizumab, including rectal fistula (0.4%), bowel perforation (0.4%) and atrial fibrillation (0.4%).

The most common adverse reactions or laboratory abnormalities (≥10% in incidence) in patients treated with single‑agent LONSURF at a rate that exceeds the rate in patients receiving placebo in mCRC: anemia (77% vs 33%), neutropenia (67% vs 0.8%), asthenia/fatigue (52% vs 35%), nausea (48% vs 24%), thrombocytopenia (42% vs 8%), decreased appetite (39% vs 29%), diarrhea (32% vs 12%), vomiting (28% vs 14%), abdominal pain (21% vs 19%), and pyrexia (19% vs 14%). In metastatic gastric cancer or gastroesophageal junction (GEJ): neutropenia (66% vs 4%), anemia (63% vs 38%), nausea (37% vs 32%), thrombocytopenia (34% vs 9%), 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: in mCRC (2% vs 0%) and in metastatic gastric cancer and GEJ (3% vs 2%).

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

The most common adverse reactions or laboratory abnormalities (≥20% in incidence) in patients treated with LONSURF in combination with bevacizumab vs LONSURF alone were neutropenia (80% vs 68%), anemia (68% vs 73%), thrombocytopenia (54% vs 29%), fatigue (45% vs 37%), nausea (37% vs 27%), increased aspartate aminotransferase (34% vs 28%), increased alanine aminotransferase (33% vs 23%), increased alkaline phosphate (31% vs 36%), decreased sodium (25% vs 20%), diarrhea (21% vs 19%), abdominal pain (20% vs 18%), and decreased appetite (20% vs 15%).

Please see accompanying full Prescribing Information.

Indications and Important Safety Information

INDICATIONS

LONSURF is indicated as a single agent or in combination with bevacizumab 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 indicated for the treatment of 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.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Severe Myelosuppression: In the 1114 patients who received LONSURF as a single agent, LONSURF caused severe or life‑threatening myelosuppression (Grade 3‑4) consisting of neutropenia (38%), anemia (17%), thrombocytopenia (4%) and febrile neutropenia (3%). Three patients (0.3%) died due to neutropenic infection/sepsis; four other patients (0.5%) died due to septic shock. A total of 14% of patients received granulocyte‑colony stimulating factors. In the 246 patients who received LONSURF in combination with bevacizumab, LONSURF caused severe or life-threatening myelosuppression (Grade 3‑4) consisting of neutropenia (52%), anemia (5%), thrombocytopenia (4%) and febrile neutropenia (0.4%). One patient (0.4%) died due to abdominal sepsis and two other patients (0.8%) died due to septic shock. A total of 29% of 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 severe myelosuppression and resume at the next lower dosage.

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 breastfed child or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, 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 older who received LONSURF as a single agent had a higher incidence of the following hematologic laboratory abnormalities compared to patients younger than 65 years: Grade 3 or 4 neutropenia (46% vs 32%), Grade 3 anemia (20% vs 14%), and Grade 3 or 4 thrombocytopenia (6% vs 3%). Patients 65 years of age or older who received LONSURF in combination with bevacizumab had a higher incidence of the following hematologic laboratory abnormalities compared to patients younger than 65 years: Grade 3 or 4 neutropenia (60% vs 46%) and Grade 3 or 4 thrombocytopenia (5% vs 4%).

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). Reduce the starting dose of LONSURF for patients with severe renal impairment (CLcr of 15 to 29 mL/min) to a recommended dosage of 20 mg/m2.

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

ADVERSE REACTIONS

Serious adverse reactions occurred in 25% of patients. The most frequent serious adverse reactions (≥2%) were intestinal obstruction (2.8%), and COVID-19 (2%). Fatal adverse reactions occurred in 1.2% of patients who received LONSURF in combination with bevacizumab, including rectal fistula (0.4%), bowel perforation (0.4%) and atrial fibrillation (0.4%).

The most common adverse reactions or laboratory abnormalities (≥10% in incidence) in patients treated with single‑agent LONSURF at a rate that exceeds the rate in patients receiving placebo in mCRC: anemia (77% vs 33%), neutropenia (67% vs 0.8%), asthenia/fatigue (52% vs 35%), nausea (48% vs 24%), thrombocytopenia (42% vs 8%), decreased appetite (39% vs 29%), diarrhea (32% vs 12%), vomiting (28% vs 14%), abdominal pain (21% vs 19%), and pyrexia (19% vs 14%). In metastatic gastric cancer or gastroesophageal junction (GEJ): neutropenia (66% vs 4%), anemia (63% vs 38%), nausea (37% vs 32%), thrombocytopenia (34% vs 9%), 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: in mCRC (2% vs 0%) and in metastatic gastric cancer and GEJ (3% vs 2%).

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

The most common adverse reactions or laboratory abnormalities (≥20% in incidence) in patients treated with LONSURF in combination with bevacizumab vs LONSURF alone were neutropenia (80% vs 68%), anemia (68% vs 73%), thrombocytopenia (54% vs 29%), fatigue (45% vs 37%), nausea (37% vs 27%), increased aspartate aminotransferase (34% vs 28%), increased alanine aminotransferase (33% vs 23%), increased alkaline phosphate (31% vs 36%), decreased sodium (25% vs 20%), diarrhea (21% vs 19%), abdominal pain (20% vs 18%), and decreased appetite (20% vs 15%).

Please see accompanying full Prescribing Information.