Taiho Oncology Presents Real-World Findings for LONSURF® at the ASCO Gastrointestinal Cancers Symposium

• 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: https://clinicaltrials.gov/ct2/show/NCT04737187.

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 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 https://www.taihooncology.com/, 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