Shots: 

• Volker Wacheck sheds light on the recent approval of Lonsurf in combination with bevacizumab for patients with metastatic colorectal cancer 

• While sharing key insights from the pivotal P-III (SUNLIGHT) trial evaluating Lonsurf ± bevacizumab, Volker reveals that the combination drug is proven to prolong both OS and PFS along with QoL benefits and a manageable safety profile 

• Volker indulges in explaining PharmaShots, the mechanism of the combination therapy, and speaks elaborately on Taiho Oncology Patient Support which aims to help patients, caregivers, and HCPs access Taiho Oncology products 

Saurabh: Let’s start discussing about the US FDA approval of Lonsurf (trifluridine/ tipiracil) combination with bevacizumab for patients with metastatic colorectal cancer.  

Volker: This approval marks a significant milestone for adult patients with metastatic colorectal cancer (mCRC), who historically have had poor outcomes and faced significant unmet medical needs. 

LONSURF in combination with bevacizumab provides patients with mCRC an important new treatment option, one that has shown to improve overall survival and progression-free survival in addition to other benefits that we’ll discuss in more detail in a moment. It is our belief that this combination of drugs may change the treatment landscape for this patient population. 

Saurabh: In what ways does this approval contribute to the evolving landscape of metastatic colorectal cancer treatment?  

Volker: LONSURF in combination with bevacizumab has been shown to prolong both overall survival (OS) and progression-free survival (PFS) along with quality-of-life benefits and a manageable safety profile. This approval by the FDA brings new hope in a disease that is, by nature, challenging to treat. 

Saurabh: Please shed some light on the pivotal Phase 3 SUNLIGHT trial evaluating Lonsurf and its combination with bevacizumab in patients with metastatic colorectal cancer. Share some invaluable insights of the trial. 

Volker: The SUNLIGHT trial is the first trial against an active control in third-line mCRC that demonstrated statistically significant efficacy and safety. 

 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 overall survival (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. 

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 OS and PFS for patients with mCRC following disease progression or intolerance on two prior chemotherapy regimens compared to LONSURF alone. 

Saurabh: Could you elaborate on the mechanism of action of Lonsurf and how their combination contributes to patient outcomes?  

Volker: 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. 

Saurabh: How is Taiho planning to ensure the accessibility and affordability of this combination therapy for patients in need?  

Volker: To, date, Medicare, Medicaid and many insurance companies are covering LONSURF in combination with bevacizumab for its FDA-aproved indication, and we continue to closely watch that.  Additionally, Taiho Oncology offers patient affordability assistance through Taiho Oncology Patient Support™ to help patients, caregivers, and healthcare professionals access Taiho Oncology products. Patient affordability assistance is only applicable to Taiho Oncology products and would not cover costs associated with bevacizumab.  

Saurabh: Are there any plans for further research or studies to explore the long-term effects or potential applications of this combination therapy beyond its current indication? 

Volker: We are in the process of evaluating the potential clinical utility of this combination in other types of cancer and the avenues to do so as part of our mission to advance patient care. 

Saurabh: There are various biosimilars available for Avastin. If one combines Lonsurf with any biosimilar of Avastin, is there any study to show the performance or what are FDA’s recommendations on the same 

Volker: FDA approval of a biosimilar means that the biosimilar has no clinically meaningful differences in terms of safety, purity, and potency from an existing FDA-approved biologic. The National Comprehensive Cancer Network® (NCCN®) states that an FDA approved biosimilar is an appropriate substitute for Avastin®. 

Avastin is a registered trademark of Genentech, Inc. 

Image Source: Canva 

About the Author: 

VOLKER WACHECK

Volker joined Taiho Oncology in May 2020 as Vice President, Clinical Development, and was promoted to Head of Clinical Development in 2023. He oversees the clinical development programs of Taiho Oncology's global oncology portfolio from first-in-human trials through registration studies and lifecycle management, including biomarker development and pharmacokinetic studies. 

Volker has more than 20 years of drug development experience in academia and industry. He is a board-certified oncologist and clinical pharmacologist by training. Prior to joining industry, Volker served as an associate professor (“Habilitation”) for clinical pharmacology and section head of a translational research team for experimental oncology and molecular pharmacology at the Medical University of Vienna, Austria. In 2011, he joined Eli Lilly and Company and held several leadership roles in early- and late phase oncology drug development for large and small compounds. This included roles as global medical lead for Verzenio® (CDK 4/6 inhibitor) and Lartruvo® (PDGFRa antibody) responsible for registration studies and the life cycle program of these drugs. To date, Volker has authored or co-authored more than 80 research articles in peer-reviewed journals.