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Important Safety Information Prescribing Information Patient Information

Metastatic GEJ/Gastric Cancer

FTD/TPI (LONSURF) is a Category 1 recommended option for third‑line or subsequent treatment for metastatic GEJ or gastric cancer per the National Comprehensive Cancer Network® (NCCN®)1,2

FTD/TPI = trifluridine/tipiracil; GEJ = gastroesophageal junction

FTD/TPI (LONSURF) is a Category 1 recommended option for third‑line or subsequent treatment for metastatic GEJ or gastric cancer per the National Comprehensive Cancer Network® (NCCN®)1,2

FTD/TPI = trifluridine/tipiracil; GEJ = gastroesophageal junction

3rd-LINE TREATMENT

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

Less than 10% of gastric cancer patients treated at 3rd-line (3L) go on to receive a 4th-line (4L) therapy3

Image showing that 10% of patients with gastric cancer moved from 3rd-line to 4th-line treatment

STUDY DESIGN

The estimate of gastric cancer 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 Gastric Cancer. The Kantar survey consisted of 58 physicians actively treating gastric cancer (collectively treating 1,769 gastric cancer patients monthly).3,7

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

Dosage
Metastatic Colorectal Cancer

Efficacy

For patients with previously treated metastatic GEJ or gastric cancer, help extend survival with LONSURF3,5,6

LONSURF® (FTD/TPI) tablets was studied in the TAGS trial5,6

LONSURF was studied in 507 patients with previously treated metastatic gastroesophageal junction (GEJ) or gastric cancer in the TAGS (TAS-102 Gastric Study) trial, a multinational, randomized, double-blind, placebo-controlled, phase 3 trial.5,6

Patients had received at least 2 prior regimens, including fluoropyrimidine, platinum agent, taxane and/or irinotecan, and HER2 therapy (in patients with HER2-positive tumors) and were refractory to or intolerant of the last prior therapy. 44% of patients taking LONSURF had undergone a previous gastrectomy.6

The primary endpoint in the TAGS trial was overall survival (OS), defined as the time (in months) from randomization until death. A key secondary endpoint was progression-free survival (PFS), defined as the time (in months) from randomization to the first radiologic confirmation of disease events from any cause. Another secondary endpoint was median time to deterioration of ECOG performance status defined as the time (in months) from randomization until the first date on which an ECOG Performance Status score of ≥ 2 was recorded.3,6

In the TAGS trial, LONSURF provided a statistically significant reduction in risk of mortality (31%)3,5,6

OS in patients with previously treated metastatic GEJ or gastric cancer3,5,6

Reduction in risk of Previously Treated metastatic gej or gastric cancer mortality with LONSURF Reduction in risk of Previously Treated metastatic gej or gastric cancer mortality with LONSURF

OS was defined as the time (in months) from randomization until death.3

mOS=median OS.

aKaplan-Meier estimates.

bMethodology of Brookmeyer and Crowley.

Help prolong progression-free survival3,5,6

LONSURF provided a statistically significant reduction in the risk of
progression or death (44%)

Secondary endpoint: reduction in the risk of progression or death in patients with previously treated metastatic GEJ or gastric cancer

Reduction in risk of Previously Treated metastatic gej or gastric cancer progression with LONSURF Reduction in risk of Previously Treated metastatic gej or gastric cancer progression with LONSURF

PFS was defined as the time (in months) from randomization to the first radiologic confirmation of disease events from any cause.3

mPFS=median PFS.

aKaplan-Meier estimates.

bPrespecified study endpoint.

Help delay time to performance status deterioration6

LONSURF provided a statistically significant reduction in risk of deterioration to ECOG performance status ≥2 (31%)*

Other secondary endpoint: Median time to deterioration of ECOG performance status to >2

Reduction in risk of Previously Treated metastatic gej or gastric cancer deterioration of ECOG with LONSURF Reduction in risk of Previously Treated metastatic gej or gastric cancer deterioration of ECOG with LONSURF

*ECOG Performance Status7

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, e.g., 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
Overall Survival

In the TAGS trial, LONSURF provided a statistically significant reduction in risk of mortality (31%)3,5,6

OS in patients with previously treated metastatic GEJ or gastric cancer3,5,6

Reduction in risk of Previously Treated metastatic gej or gastric cancer mortality with LONSURF Reduction in risk of Previously Treated metastatic gej or gastric cancer mortality with LONSURF

OS was defined as the time (in months) from randomization until death.3

mOS=median OS.

aKaplan-Meier estimates.

bMethodology of Brookmeyer and Crowley.

Progressive-free
Survival

Help prolong progression-free survival3,5,6

LONSURF provided a statistically significant reduction in the risk of
progression or death (44%)

Secondary endpoint: reduction in the risk of progression or death in patients with previously treated metastatic GEJ or gastric cancer

Reduction in risk of Previously Treated metastatic gej or gastric cancer progression with LONSURF Reduction in risk of Previously Treated metastatic gej or gastric cancer progression with LONSURF

PFS was defined as the time (in months) from randomization to the first radiologic confirmation of disease events from any cause.3

mPFS=median PFS.

aKaplan-Meier estimates.

bPrespecified study endpoint.

ECOG Performance Status

Help delay time to performance status deterioration6

LONSURF provided a statistically significant reduction in risk of deterioration to ECOG performance status ≥2 (31%)*

Other secondary endpoint: Median time to deterioration of ECOG performance status to >2

Reduction in risk of Previously Treated metastatic gej or gastric cancer deterioration of ECOG with LONSURF Reduction in risk of Previously Treated metastatic gej or gastric cancer deterioration of ECOG with LONSURF

*ECOG Performance Status7

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, e.g., 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

Safety

A demonstrated safety profile can help manage expectations5,6

Safety results seen in patients with metastatic GEJ or gastric cancer were consistent with those in patients with mCRC5,6

Hematologic abnormalities5,6

LONSURF +
BSC (n=335), %		 LONSURF +
BSC (n=168), %
All Gra Gr 3‐4 All Gra Gr 3‐4
Neutropenia 66 38 4 0
Anemiab 63 19 38 7
Thrombocytopenia 34 6 9 0
Febrile neutropenia 2 2 0 0
  • aWorst Grade ≥1 grade higher than baseline,with percent based on number of patients with post-baseline samples which may be <335 (LONSURF) OR 168 (placebo).
  • bAnemia: No Grade 4 definition in National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v4.03.

What else was discovered in the TAGS trial?

  • 11% of patients required a dose reduction. The most common adverse events or lab abnormalities leading to dose reduction were neutropenia, anemia, febrile neutropenia, and diarrhea5
  • 42% of patients treated with LONSURF had a dose delay of ≥4 days3
  • 16% of patients in the LONSURF group received granulocyte-colony stimulating factor (G-CSF)6
  • 13% of patients receiving LONSURF discontinued treatment due to an AE (any grade) vs 17% of patients receiving placebo5,6

No new safety signals for LONSURF® (FTD/TPI) tablets were discovered in the TAGS trial6

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

LONSURF +
BSC (n=335), %		 LONSURF +
BSC (n=168), %
All Gr Gr 3‐4a All Gr Gr 3‐4o
Gastrointestinal
Nausea 37 3 32 3
Vomiting 25 4 20 2
Diarrhea 23 3 14 2
Metabolism and nutrition
Decreased appetite 34 9 31 7
Infectionsb 23 5 16 5
  • aNo Grade 4 definition for nausea or fatigue in National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
  • 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 TAGS trial?

  • 11% of patients required a dose reduction. The most common adverse events or lab abnormalities leading to dose reduction were neutropenia, anemia, febrile neutropenia, and diarrhea3
  • 42% of patients treated with LONSURF had a dose delay of ≥4 days3
  • 16% of patients in the LONSURF group received granulocyte-colony stimulating factor (G-CSF)6
  • 13% of patients receiving LONSURF discontinued treatment due to an AE (any grade) vs 17% of patients receiving placebo5,6

No new safety signals for LONSURF® (FTD/TPI) tablets were discovered in the TAGS trial6

TAGS Trial
Study Design

LONSURF® (FTD/TPI) tablets was studied in the TAGS trial5,6

TAGS was a multinational, randomized, double-blind, placebo-controlled, phase 3 trial (N=507)6

Inclusion criteria6

  • Age ≥18 years (≥20 years in Japan)
  • Histologically confirmed, nonresectable metastatic GEJ or gastric cancer
  • ECOG performance status of 0 or 1
  • Received postoperative adjuvant chemotherapy and radiotherapy, or pre and postoperative adjuvant chemotherapy if they had recurrence <6 months of completion of the adjuvant chemotherapy
  • Received at least 2 prior regimens, including:
  • Fluoropyrimidine
  • Platinum agent
  • Taxane and/or irinotecan
  • HER2 therapy in patients with HER2-positive tumors
  • Were refactory to/intolerant of last prior therapy

2:1 Randomization6

LONSURF + BEST SUPPORTIVE CARE (n=337)

35 mg/m2/dose (up to 80 mg/dose) twice daily after meals on days 1-5 and 8-12 of each 28-day cycle

PLACEBO + BEST SUPPORTIVE CARE (n=170)

Twice daily after meals on days 1-5 and 8-12 of each 28-day cycle

After the first dose of study medication, all patients were followed for progression at scheduled 8-week intervals withde computed tomography (CT) until progression. After the end of treatment, all patients were followed up for survival every 4 weeks until death or loss to follow-up, or until the targeted number of events (deaths) was met.6

Patient Demographics

Baseline characteristics of patients in the TAGS trial6

LONSURF (N=337) Placebo (N=170)
Age, years
<65 54% 56%
Sex
Male 75% 69%
Female 25% 31%
ECOG performance status
0 36% 40%
1 64% 60%
HER2 status
Positive 20% 16%
Negative 61% 62%
Number of prior therapies
2 prior therapies 37% 38%
3 prior therapies 40% 35%
≥4 prior therapies 23% 27%
Primary site
Gastric 71% 71%
GEJ 29% 28%
Number of metastatic sites
1-2 46% 42%
≥3 54% 58%
Prior systemic treatments
Platinum therapy 100% 100%
Fluoropyrimidine-based therapy >99%* 100%
Taxane therapy† 92% 87%
Irinotecan therapy† 54% 58%
Ramucirumab therapy 34% 32%
Anti-HER2 therapy 18% 14%
Immunotheray (anti-PD-1/PD-L1) 7% 4%
Prior treatments
Gastrectomy 44% 44%

*One patient did not receive a fluoropyrimidine.

†All patients received irinotecan or taxane or both.

NCCN Clinical
Practice Guidelines
In Oncology
(NCCN Guidelines®)
for Metastatic GEJ
or Gastric Cancer

Category 1
Trifluridine and
tipiracil (LONSURF)
is recommended
as a third‑line or subsequent treatment option
for metastatic GEJ or gastric cancer1,2

The National Comprehensive Cancer Network® (NCCN®) recommends trifluridine and tipiracil (LONSURF®) as a potential third‑line or subsequent treatment option in patients with metastatic GEJ or gastric cancer. See below for a potential treatment algorithm.1,2

Sample* Treatment Algorithm (third‑line use)1,2

NCCN Guidelines for Metastatic GEJ or Gastric Cancer Treatment NCCN Guidelines for Metastatic GEJ or Gastric Cancer Treatment

This suggested treatment plan is for patients with an ECOG performance status ≤2.

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

†For HER2–overexpressing metastatic adenocarcinoma.

Category 1: Based upon high-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 Gastric Cancer V.4.2021 and the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Esophageal and Esophagogastric Cancers V.4.2021. © 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 Gastric Cancer V.4.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed September 21, 2021. To view the most recent and complete version of the guidelines, go online to NCCN.org. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Esophageal and Esophagogastric Junction Cancers V.4.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed September 21, 2021. To view the most recent and complete version of the guidelines, 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. Shitara K, Doi T, Dvorkin M, et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018;19(11):1437-1448. 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.

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.