Rectal Fistula

Real-world studies confirm that pairing LONSURF with bevacizumab increases efficacy in patients with metastatic colorectal cancer Increased efficacy with the combination was demonstrated broadly across this population and specifically in Black patients with the disease PRINCETON, N.J., Jan. 24, 2025 /PRNewswire/ -- Taiho Oncology, Inc., a company developing and commercializing novel treatments for hematologic malignancies and solid tumors, announced that it will share real-world data about the crucial role of LONSURF® (trifluridine/tipiracil) in a combination treatment for metastatic colorectal cancer (mCRC) during the American Society of Clinical Oncology 2025 Gastrointestinal Cancers Symposium, January 23-25 in San Francisco. In two abstracts, Taiho will present findings from real-world retrospective studies demonstrating that pairing LONSURF with bevacizumab, rather than administering LONSURF alone, improves clinical outcomes for the mCRC patient population, including Black patients. Orally administered LONSURF pairs the chemotherapy trifluridine, a nucleoside metabolic inhibitor, with tipiracil hydrochloride, a thymidine phosphorylase inhibitor that prolongs trifluridine's ability to stay active in the body. In the U.S., LONSURF's indication in mCRC is for use alone or in combination with bevacizumab, an anti-angiogenic drug. "We're pleased to present substantial real-world evidence confirming LONSURF's role as an effective regimen for patients with metastatic colorectal cancer," said Tehseen Salimi, MD, MHA, Senior Vice President and Head of Medical Affairs, Taiho Oncology. "At Taiho Oncology, we are dedicated to improving clinical outcomes and reducing patient burden by analyzing the real-world impact of our treatments and making patients and providers aware of the results." Adding bevacizumab to LONSURF improves clinical outcomes for patients with mCRC The larger of the two studies included 3,680 adult patients with mCRC, 3,151 of whom received LONSURF alone and 529 of whom received LONSURF plus bevacizumab. Researchers pulled data about patients and their treatments from electronic medical records and claims in the ConcertAI RWD360™ dataset. Investigators found that patients who took LONSURF plus bevacizumab, in the usual care setting, experienced a median real-world overall survival of 9.4 months (95% confidence interval [CI] 8.0-10.1) versus 6.4 months (95% CI 6.1-6.6; p<0.0001) in patients who took LONSURF alone, a statistically significant improvement. In addition, in a model that adjusted for certain patient characteristics, the risk of death was significantly decreased in the LONSURF/bevacizumab cohort versus the LONSURF monotherapy cohort, with a hazard ratio of 0.68 (p ˂0.0001) favoring the combination treatment. The investigators also found that the combination regimen, compared with LONSURF alone, significantly prolonged treatment duration (median 3.5 [95% CI: 3.3-3.8] vs 2.4 [95% CI: 2.3-2.6] months, respectively; p<0.0001) and, in the adjusted model, time to next treatment or death (median 5.0 [95% CI: 4.6-5.5] vs 3.9 [95%CI: 3.8-4.1] months; p<0.0001; HR=0.73; p<0.0001). Also using the adjusted model, the team found a decreased risk of treatment discontinuation with the combination regimen (HR=0.65; p<0.0001). Pairing LONSURF with bevacizumab improves real-world overall survival in Black patients with mCRC The second study included 639 Black patients with mCRC, 551 of whom received LONSURF alone and 88 of whom received LONSURF plus bevacizumab. Patient data was collected via United States-based electronic medical records and claims in the ConcertAI RWD360™ dataset. Investigators observed a significant improvement in real-world overall survival with LONSURF plus bevacizumab as compared with LONSURF alone (10.8 vs 6.2 months, respectively; p=0.0001). In addition, in an adjusted model, participants who received the combination treatment experienced a significantly lower risk of death compared with those who received LONSURF monotherapy (HR=0.45; p<0.0001). Researchers also found that treatment duration was significantly prolonged with LONSURF plus bevacizumab compared with LONSURF alone (3.8 vs 2.4 months, respectively; p<0.0001). In the adjusted model, participants who received the combination regimen had about half the risk of discontinuation compared with those who received LONSURF alone (HR=0.51; p<0.0001). "These are the largest real-world studies so far to confirm the findings of the Phase 3 SUNLIGHT trial, which demonstrated that LONSURF paired with bevacizumab, versus LONSURF alone, improved overall survival in patients with treatment-refractory metastatic colorectal cancer," said Harold Keer, MD, PhD, Chief Medical Officer, Taiho Oncology. "Our findings will particularly inform the treatment of Black patients with metastatic colorectal cancer, who are under-represented in clinical trials despite having a much higher incidence and higher mortality of colorectal cancer as compared to other patients, helping to reinforce the importance of a representative patient population throughout clinical development to provide safe and effective treatments for all patients." About the SUNLIGHT Trial SUNLIGHT is a multinational, randomized, active-controlled, open-label, two-arm Phase 3 clinical trial to investigate the efficacy and safety of trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil alone, in patients with refractory mCRC following two chemotherapy regimens. A total of 492 patients were randomly allocated (in a 1:1 ratio) to receive trifluridine/tipiracil in combination with bevacizumab or trifluridine/tipiracil monotherapy. The primary objective was to assess trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil alone, in terms of OS (primary endpoint). Key secondary endpoints were PFS, overall response rate (ORR), disease control rate (DCR) and quality of life (QoL), as well as the safety and tolerability of trifluridine/tipiracil used in combination with bevacizumab in comparison with trifluridine/tipiracil monotherapy. The SUNLIGHT trial was conducted by Servier and Taiho Oncology, Inc. For more information on SUNLIGHT, please visit: . About LONSURF LONSURF is an oral nucleoside antitumor agent discovered and developed by Taiho Pharmaceutical Co., Ltd. LONSURF consists of a thymidine-based nucleoside analog, trifluridine, and the thymidine phosphorylase (TP) inhibitor, tipiracil, which increases trifluridine exposure by inhibiting its metabolism by TP. Trifluridine is incorporated into DNA, resulting in DNA dysfunction and inhibition of cell proliferation. 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 r eactions 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 were 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%). 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. About Taiho Oncology, Inc. The mission of Taiho Oncology, Inc. is to improve the lives of patients with cancer, their families and their caregivers. The company specializes in the development and commercialization of orally administered anti-cancer agents for various tumor types. Taiho Oncology has a robust pipeline of small molecule clinical candidates targeting solid tumor and hematological malignancies, with additional candidates in pre-clinical development. Taiho Oncology is a subsidiary of Taiho Pharmaceutical Co., Ltd. which is part of Otsuka Holdings Co., Ltd. Taiho Oncology is headquartered in Princeton, New Jersey and oversees its parent company's European and Canadian operations, which are located in Baar, Switzerland and Oakville, Ontario, Canada. For more information, visit , and follow us on LinkedIn and X. Taiho Oncology and the Taiho Oncology logo are registered trademarks of Otsuka Holdings Co., Ltd. or its subsidiaries. Taiho Oncology Contact: Leigh Labrie (609) 664-9878 [email protected] SOURCE Taiho Oncology WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Mesenchymal stem cells (MSCs) have broad therapeutic potential for treating inflammation and degenerative diseases. Mesenchymal stem cells have been isolated and identified from many other sources of human tissues, widely distributed in virtually all tissues (including fetal and adult), such as bone marrow, blood, umbilical cord, placenta, fat, amnion, amniotic fluid, dental pulp, skin, menstrual blood, and so on. Mesenchymal stem cell therapy works in both direct and indirect ways. The direct actions include homing, directed differentiation, multipotent differentiation, and paracrine effects. The indirect actions involve the bidirectional regulation of immune responses and inflammation, antioxidative stress, antifibrosis, antiapoptosis, hematopoiesis support, participation in or promotion of angiogenesis, activation of the proliferation and differentiation of endogenous stem cells, and the dedifferentiation of diseased tissue organs' normal cells, as well as anti-aging, and anti-scar formation. The application of mesenchymal stem cell therapy in clinical practice is very broad, including the treatment of hematological diseases, neurological diseases, digestive diseases, cardiovascular diseases, respiratory diseases, skeletal system diseases, endocrine system diseases, immune system diseases, urogenital diseases, as well as anti-aging and immune enhancement. With the continuous investment in future scientific research, it is believed that there will be increasingly more difficult and complex diseases starting to explore the use of mesenchymal stem cells for treatment, and an increasing number of new drugs based on mesenchymal stem cells will be approved for clinical trials and even applications. Mesenchymal Stem Cell Therapy Competitive LandscapeAccording to Patsnap Synapse, as of 8 Oct 2023, there are a total of 339 Mesenchymal stem cell therapy drugs worldwide, from 320 organizations, covering 11 targets, 299 indications, and conducting 1254 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications,  targets, organizations, clinical trials, and clinical results related to this drug type. Phase II Clinical Trial of Mesenchymal Stem Cell Therapy Medicinal: ADR-001ADR-001 is a mesenchymal stem cell therapy drug that targets ADAR. Mesenchymal stem cells are multipotent cells that can differentiate into various cell types, including those found in the immune system, urogenital system, and digestive system. ADAR, or adenosine deaminase acting on RNA, is an enzyme involved in RNA editing. The therapeutic areas for ADR-001 include immune system diseases, urogenital diseases, and digestive system disorders. Immune system diseases encompass a wide range of conditions that affect the body's immune response, such as autoimmune diseases and immunodeficiency disorders. Urogenital diseases refer to disorders affecting the urinary and reproductive systems, including conditions like urinary tract infections and infertility. Digestive system disorders involve issues with the gastrointestinal tract, such as inflammatory bowel disease and liver diseases. The active indications for ADR-001 are liver cirrhosis, glomerulonephritis, and IGA. Liver cirrhosis is a chronic liver disease characterized by the replacement of healthy liver tissue with scar tissue, leading to impaired liver function. Glomerulonephritis is a group of kidney diseases that cause inflammation in the glomeruli, the tiny filters in the kidneys. IGA refers to immunoglobulin A, an antibody that plays a role in the immune response. Elevated levels of IGA can be associated with certain diseases, including kidney and liver disorders. Rohto Pharmaceutical Co., Ltd. is the originator organization of ADR-001. They are responsible for the development and research of this drug. The highest phase of development for ADR-001 is Phase 2, indicating that it has undergone initial testing for safety and efficacy in a limited number of patients. In summary, ADR-001 is a mesenchymal stem cell therapy drug developed by Rohto Pharmaceutical Co., Ltd. It targets ADAR and is being investigated for its potential in treating immune system diseases, urogenital diseases, and digestive system disorders. The active indications for ADR-001 include liver cirrhosis, glomerulonephritis, and IGA. Currently, ADR-001 is in Phase 2 of development, suggesting that further clinical trials are required to assess its effectiveness and safety. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Approved Mesenchymal Stem Cell Therapy Medicinal: StempeuticsMesenchymal stem cell therapies, specifically Stempeutics, are a type of drug used in the field of biomedicine. These therapies are designed to treat various medical conditions related to the digestive system, nervous system, cardiovascular system, endocrinology and metabolism, as well as skin and musculoskeletal diseases. The active indications for Stempeutics include osteoarthritis, diabetic foot, and rectal fistula. These conditions are targeted by the drug to provide therapeutic benefits and alleviate symptoms associated with them. In terms of its development stage, Stempeutics has reached the highest phase of approval, indicating that it has successfully undergone rigorous testing and evaluation. The first approval of Stempeutics was granted in August 2020 in India. This means that India was the first country/location to approve the drug for use in patients. This approval signifies that the regulatory authorities in India have reviewed the clinical data and determined that the drug meets the necessary standards for safety and effectiveness. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Overall, Stempeutics is a mesenchymal stem cell therapy that has been approved for the treatment of osteoarthritis, diabetic foot, and rectal fistula. It has shown promising results in clinical trials and has received approval in India. The drug holds potential for addressing various medical conditions related to the digestive system, nervous system, cardiovascular system, endocrinology and metabolism, as well as skin and musculoskeletal diseases.

Approval is based on data from a pivotal clinical trial showing that treatment with LONSURF plus bevacizumab resulted in statistically significant and clinically meaningful improvements in overall survival in patients with previously treated mCRC compared to LONSURF as a single agent PRINCETON, N.J., Aug. 2, 2023 /PRNewswire/ -- Taiho Oncology, Inc. and Taiho Pharmaceutical Co., Ltd. announced today that the U.S. Food and Drug Administration (FDA) has approved LONSURF® (trifluridine/tipiracil) as a single agent or in combination with bevacizumab for the treatment of adult patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. Continue Reading Taiho Pharmaceutical "The FDA approval of this combination provides patients with mCRC an important new treatment option, one that has been shown to extend life in addition to other benefits and which I believe will change the treatment landscape for this patient population," said Marwan Fakih, MD, Professor, Medical Oncology and Therapeutics Research, City of Hope, Duarte, Calif., and lead U.S. investigator for the pivotal Phase 3 SUNLIGHT trial that evaluated this combination. "Notably, the use of LONSURF plus bevacizumab in these patients did not result in an increase in potentially intolerable side effects that might limit the utility of this combination." The results from the Phase 3 SUNLIGHT trial, which were published in the New England Journal of Medicine in May 2023, demonstrated that the combination of LONSURF plus bevacizumab provided statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) for patients with mCRC following disease progression or intolerance on two prior chemotherapy regimens compared to LONSURF alone.1 This was the first Phase 3 study against an active control in third-line mCRC that demonstrated statistically significant efficacy and safety. Key results include: Median OS was 10.8 months in the LONSURF plus bevacizumab arm versus 7.5 months in the LONSURF arm (hazard ratio [HR]: 0.61, 95% confidence interval [CI]: 0.49-0.77, p<0.001).1 This improvement in OS represented a 39% reduction in the risk of death in patients with mCRC.1 The median PFS was 5.6 months in the LONSURF plus bevacizumab arm versus 2.4 months in the LONSURF arm (HR: 0.44, 95% CI: 0.36-0.54, p<0.001), indicating a 56% relative risk reduction of disease progression.1 Results were consistent across subgroups regardless of age, sex, location of primary disease, number of metastatic sites, KRAS mutation status, and prior bevacizumab treatment.1 Median time to worsening of the ECOG performance status score from 0 or 1 to 2 or more was 9.3 months (95% CI: 8.3-10.6) in the LONSURF plus bevacizumab arm versus 6.3 months (95% CI: 5.6-7.2) in the LONSURF arm (HR: 0.54, 95% CI: 0.43-0.67).1 The OS and PFS benefits of LONSURF plus bevacizumab were associated with maintenance of quality of life from baseline to cycle 6 and no clinically relevant changes in mean scores were observed in any subdomains for EORTC QLQ-C30 and EuroQol EQ-5D-5L health-related quality of life questionnaires.2 The combination of LONSURF plus bevacizumab had a manageable safety profile as was expected based on the known profile of each agent.1 The most frequent severe treatment emergent adverse events for LONSURF plus bevacizumab versus LONSURF alone were neutropenia (43.1% vs 32.1%) and anemia (6.1% vs 11.0%), respectively.1 "The treatment of advanced colorectal cancer has been a core focus of our work at Taiho Oncology since our inception and with good reason: approximately 22% of patients3 with colorectal cancer in the U.S. are diagnosed after the cancer has metastasized," said Timothy Whitten, President and Chief Executive Officer, Taiho Oncology, Inc. "The FDA approval of LONSURF in combination with bevacizumab is another example of how we are continuing to advance care in this disease and provide new hope to patients and their families." In 2023, the National Comprehensive Cancer Network® (NCCN®) Drugs and Biologics Compendium (NCCN Compendium®) for Colon Cancer and Rectal Cancer was updated to include a Category 2A recommendation for trifluridine/tipiracil as subsequent therapy, either single agent or in combination with bevacizumab (preferred) (per NCCN®, an FDA-approved biosimilar is an appropriate substitute for bevacizumab),a as treatment options for patients who have progressed through all available regimens besides regorafenib or trifluridine/tipiracil with or without bevacizumab.3,4 "From Taiho Pharmaceutical's initial discovery of LONSURF to this latest regulatory milestone, we are appreciative of the investigators and patients who helped to contribute to our growing body of knowledge of this important therapeutic through their participation in our clinical development programs," said Fabio Benedetti, MD, Global Chief Medical Officer for Oncology, Taiho Pharmaceutical Co., Ltd. "And now we look forward to supporting healthcare professionals in the treatment of patients with mCRC who may be candidates for treatment with LONSURF in combination with bevacizumab." On July 31, 2023, Servier, which conducted the SUNLIGHT trial with Taiho Oncology, received approval from the European Commission for LONSURF in combination with bevacizumab for the treatment of adult patients with mCRC who have received two prior anti-cancer treatment regimens, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapies, anti-VEGF agents, and/or anti-EGFR agents. The Marketing Authorization covers the 27 countries of the European Union as well as Iceland, Northern Ireland, Liechtenstein and Norway. About the SUNLIGHT Trial1 SUNLIGHT is a multinational, randomized, active-controlled, open-label, two-arm Phase 3 clinical trial to investigate the efficacy and safety of LONSURF plus bevacizumab versus LONSURF alone, in patients with metastatic colorectal cancer following two chemotherapy regimens. A total of 492 patients were randomly allocated (in a 1:1 ratio) to receive LONSURF in combination with bevacizumab or LONSURF monotherapy. The primary objective was to assess LONSURF plus bevacizumab versus LONSURF alone in terms of OS (primary endpoint). Key secondary endpoints were PFS, overall response rate (ORR), disease control rate (DCR) and quality of life (QoL), as well as the safety and tolerability of LONSURF used in combination with bevacizumab in comparison with LONSURF monotherapy. For more information on SUNLIGHT, please visit: . About Colorectal Cancer Colorectal cancer is the third most commonly diagnosed cancer in the U.S.5 In 2023, there will be an estimated 153,020 new cases and 52,550 deaths in the U.S.6 Approximately 22% of U.S. patients are diagnosed after their cancer has metastasized.3 The relative five-year survival rate for patients with metastatic colorectal cancer is 14%.3 About LONSURF LONSURF is an oral nucleoside antitumor agent discovered and developed by Taiho Pharmaceutical Co., Ltd. LONSURF consists of a thymidine-based nucleoside analog, trifluridine, and the thymidine phosphorylase (TP) inhibitor, tipiracil, which increases trifluridine exposure by inhibiting its metabolism by TP. Trifluridine is incorporated into DNA, resulting in DNA dysfunction and inhibition of cell proliferation. 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 were 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%). 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. About Taiho Oncology, Inc. The mission of Taiho Oncology, Inc. is to improve the lives of patients with cancer, their families and their caregivers. The company specializes in the development of orally administered anti-cancer agents and markets these medicines for a range of tumor types in the U.S. Taiho Oncology's growing pipeline of antimetabolic and selectively targeted anti-cancer agents is led by a world-class clinical development organization. Taiho Oncology is a subsidiary of Taiho Pharmaceutical Co., Ltd. which is part of Otsuka Holdings Co., Ltd. Taiho Oncology is headquartered in Princeton, New Jersey and oversees its parent company's European and Canadian operations, which are located in Zug, Switzerland and Oakville, Ontario, Canada. For more information, visit . About Taiho Pharmaceutical Co., Ltd. Taiho Pharmaceutical, a subsidiary of Otsuka Holdings Co., Ltd. (), is an R&D-driven specialty pharma with a focus on oncology. Taiho Pharmaceutical also has development programs in allergy and immunology, and consumer healthcare products. Our corporate philosophy takes the form of a pledge: "We strive to improve human health and contribute to a society enriched by smiles." For more information about Taiho Pharmaceutical, please visit: . LONSURF is a registered trademark of Taiho Pharmaceutical Co., Ltd. Taiho Oncology Media Contact: Judy Kay Moore Taiho Oncology, Inc. 574-526-2369 [email protected] Taiho Pharmaceutical Media Contact: Junko Onishi Taiho Pharmaceutical Co., Ltd. +81-3293-2878 [email protected] LON-PM-US-1711 08/23 a Regorafenib or trifluridine + tipiracil with or without bevacizumab are treatment options for patients who have progressed through all available regimens. 1 Prager GW, Taieb J, Fakih M, et al. Trifluridine–tipiracil and bevacizumab in refractory metastatic colorectal cancer. New England Journal of Medicine. 2023;388(18):1657-1667. Last accessed: July 2023. 2 Prager G, Taieb J, Fakih M, et al. O-9 health-related quality of life associated with trifluridine/tipiracil in combination with bevacizumab in refractory metastatic colorectal cancer: An analysis of the phase 3 sunlight trial. Annals of Oncology. 2023;34. Last accessed July 2023. . 3 Wang J, Li S, Liu Y, Zhang C, Li H, Lai B. Metastatic patterns and survival outcomes in patients with stage IV colon cancer: A population-based analysis. Cancer Med. 2020;9(1):361-373. Last accessed: July 2023. . 4 National Comprehensive Cancer Network. National Comprehensive Cancer Network® Drugs and Biologics Compendium (NCCN Compendium®) for Colon Cancer (Version 2.2023-April 25, 2023) and Rectal Cancer (Version 3.2023-May 26, 2023). Last accessed July 2023. . 5 Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. American Cancer Society CA: A Cancer Journal for Clinicians. 2023;73(1):17-48. Last accessed: July 2023. . 6 National Cancer Institute Surveillance Epidemiology and End Results Program. Cancer Stat Facts: Colorectal Cancer. SEER. Last accessed July 13, 2023. . SOURCE Taiho Oncology, Inc.