Infigratinib: A Game Changer in Urothelial Carcinoma Therapy

  • Infigratinib, an FGFR1-3 inhibitor, has shown promise as an adjuvant therapy for invasive urothelial carcinoma.

  • The FDA has approved infigratinib (Truseltiq) for the treatment of previously treated, FGFR2 fusion or other rearrangement-positive cholangiocarcinoma.

  • Urothelial carcinoma is a common form of urinary tract cancer. When invasive, it can lead to serious health complications.

  • FGFR3 alterations are common in invasive urothelial carcinoma and may serve as significant biomarkers for patient stratification and targeted therapy.

  • The PROOF 302 study suggests infigratinib could significantly improve disease-free survival in patients with FGFR3-altered invasive urothelial carcinoma.

  • Pembrolizumab is another valuable treatment option for urothelial carcinoma, providing hope for patients and physicians alike.

  • Futibatinib carries its unique side effect profile that should be carefully considered in treatment decisions.

  • Petros Grivas, MD insights highlight the importance of personalized medicine approaches targeting specific molecular abnormalities, emphasizing the future potential of targeted therapies.

Urothelial carcinoma, a type of cancer that typically affects the cells that line the urinary tract, represents a significant health concern worldwide. The American Cancer Society estimates that over 83,000 new cases of bladder cancer, a type of urothelial carcinoma, will be diagnosed in the United States in 2023 alone.

Despite significant advances in medical science, high recurrence rates and limitations in treatment options present a major challenge in managing this disease.

In this context, novel treatment strategies such as targeted therapy are gaining increased attention.

The focus today is Infigratinib, a promising drug currently under investigation for its potential role in treating urothelial carcinoma. As a selective inhibitor of the fibroblast growth factor receptor (FGFR) family of proteins.

The role of FGFR3, one of the members of the FGFR family, is of particular interest in urothelial carcinoma.

This protein is often altered in urothelial carcinoma patients, thereby disrupting normal cell functioning and promoting the growth of cancer cells. Recognizing this, researchers have been keen to explore therapies that target FGFR3, with Infigratinib emerging as a potent candidate.

Overview of Infigratinib

Infigratinib, also known by its brand name Truseltiq, is a novel drug that is generating considerable interest in the oncology community.

What is Infigratinib Used For?

Primarily, Infigratinib is used for its potent ability to inhibit the Fibroblast Growth Factor Receptor (FGFR) family of proteins.

In the context of cancer, these proteins often undergo genetic alterations that disrupt their normal functioning and contribute to the growth and spread of cancer cells.

By targeting and inhibiting these proteins, Infigratinib offers a promising new strategy to treat cancers with these specific genetic alterations.

What Category is Infigratinib?

Infigratinib belongs to the class of drugs known as kinase inhibitors, more specifically, it is an FGFR kinase inhibitor.

Kinase inhibitors, as their name suggests, work by blocking the action of kinases – enzymes that play a critical role in various cellular processes, including cell growth and division.

In many cancers, these enzymes are overactive, leading to uncontrolled cell proliferation – a hallmark of cancer.

What is the Mechanism of Action of Infigratinib?

Infigratinib works by selectively inhibiting FGFR1-3, members of the FGFR family of proteins.

These proteins play a crucial role in cell proliferation, survival, migration, and differentiation. However, when genetically altered, they can promote the development and progression of cancer.

In patients with FGFR genetic alterations, Infigratinib can effectively bind to and inhibit these proteins.

How do FGFR Inhibitors Work?

FGFR inhibitors like Infigratinib work by blocking the activity of FGFR proteins, which are often altered in cancer.

These alterations can lead to the overactivation of FGFR signaling pathways, promoting the growth and survival of cancer cells.

FGFR inhibitors bind to these proteins, blocking their activity and thereby interrupting the signaling pathways, leading to reduced growth and potential death of the cancer cells.

Understanding Infigratinib and its mechanism of action is key to appreciating the potential this drug has in transforming the treatment landscape for cancers associated with FGFR alterations, such as urothelial carcinoma.

Infigratinib and FDA Approval

The journey of a drug from the lab bench to the patient's bedside is a long and meticulous process, requiring rigorous testing and validation.

A crucial milestone in this journey is the approval from regulatory bodies such as the U.S. Food and Drug Administration (FDA), which ensures that the drug is safe and effective for its intended use.

Is Infigratinib FDA Approved?

Yes, Infigratinib has received FDA approval, but not for all indications.

In May 2021, the FDA approved Infigratinib (under the brand name Truseltiq) for the treatment of adults with locally advanced or metastatic urothelial carcinoma that has a type of susceptible genetic alteration known as FGFR3 or FGFR2, and that has progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

This marked a significant development as Truseltiq is the first FGFR kinase inhibitor approved by the FDA.

Understanding Urothelial Carcinoma

Urothelial carcinoma, also known as transitional cell carcinoma, is a type of cancer that primarily affects the urothelium, a layer of cells that line the urinary system.

This includes:

  • The bladder

  • Ureters

  • Renal pelvis

What is Urothelial Carcinoma?

Urothelial carcinoma is the most common type of bladder cancer and the sixth most common type of cancer in the United States. While it most frequently affects the bladder, it can also occur in other parts of the urinary tract, including the ureters and the renal pelvis.

What Causes Urothelial Carcinoma?

Like other cancers, urothelial carcinoma occurs when normal cells in the urothelium undergo changes that cause them to grow uncontrollably, forming a mass or tumor.

The exact cause of these changes is not known, but several risk factors have been identified.

These include smoking, exposure to certain industrial chemicals, long-term use of certain pain medications, and a history of bladder infections.

What is Invasive Urothelial Carcinoma?

When urothelial carcinoma is described as "invasive," it means that the cancer has spread beyond the inner layer of the bladder wall to the deeper layers.

Invasive urothelial carcinoma is more serious than non-invasive forms of the disease because it has a higher risk of spreading to other parts of the body.

Treating Urothelial Carcinoma: The Role of Infigratinib

In the context of treating urothelial carcinoma, the potential role of Infigratinib as a targeted therapy is currently a hot topic of research.

FGFR3 genetic alterations occur in a significant proportion of urothelial carcinomas, making it a potential target for therapy.

The PROOF 302 trial, which we will explore in detail later in this article, has been designed to investigate the efficacy and safety of Infigratinib as a targeted therapy in patients with invasive urothelial carcinoma and FGFR3 alterations.

In-depth Look at the PROOF 302 Study

As the medical community continues to investigate targeted therapies in cancer treatment, the PROOF 302 study stands out as a groundbreaking trial examining the efficacy of infigratinib as adjuvant therapy in patients with invasive urothelial carcinoma harboring FGFR3 alterations.

Understanding the PROOF 302 Study

PROOF 302 is a randomized, double-blind, placebo-controlled, phase III study aimed to investigate the efficacy and safety of infigratinib (Truseltiq) in comparison to a placebo.

The study involves approximately 218 adult patients with high-risk invasive urothelial carcinoma with FGFR3 genetic alterations, who have undergone surgical resection and are ineligible for cisplatin-based adjuvant chemotherapy or with residual disease after cisplatin-based neoadjuvant therapy.

Study Methodology

Participants in the PROOF 302 study receive oral infigratinib 125 mg or placebo (in a 1:1 ratio) once daily on days 1–21 of a 28-day cycle, for up to 52 weeks or until disease recurrence, unacceptable toxicity, or death.

It's worth noting that the enrollment began in January 2020 and involves about 120 centers worldwide.

Primary and Secondary Endpoints of the Study

The primary endpoint of the PROOF 302 study is disease-free survival (DFS), as reviewed centrally.

The secondary endpoints include DFS with low-risk intraluminal recurrence included; metastasis-free survival; overall survival; DFS as per investigator review; and safety and tolerability.

The study also includes several exploratory endpoints, including an assessment of patients' quality of life, pharmacokinetics, and analysis of cell-free DNA (cfDNA) and/or RNA to study potential mechanisms of resistance.

Why is the PROOF 302 Study Important?

The PROOF 302 study is of considerable significance in the field of oncology, particularly for patients with invasive urothelial carcinoma harboring FGFR3 alterations.

Its results could potentially open new avenues for targeted therapy for this patient population, many of whom are unable to receive cisplatin-based adjuvant chemotherapy.

It is important to keep abreast of new developments and research outcomes regarding the PROOF 302 study and other similar studies that are pushing the boundaries of cancer treatment.

Insights from Petros Grivas, MD, PhD

In the oncology field, we stand on the shoulders of giants. Dr. Petros Grivas, a leading researcher in urothelial carcinoma at Washington University, has offered game-changing insights into the treatment of invasive UC with his work on the PROOF 302 trial and the role of FGFR3 alterations. His dedication has broadened our understanding and paved the way for innovative, targeted treatment strategies. Don't miss this opportunity to learn from one of the best in the field. Watch the interview with Petros Grivas, MD, PhD during the ASCO 2023 today and enhance your knowledge on this significant topic:




The realm of oncology is an ever-evolving field, one that continues to offer new paths for the treatment of urothelial carcinoma. Central to this ongoing journey is the development and use of targeted therapies like infigratinib.

Approved by the FDA for treating cholangiocarcinoma, infigratinib, also known as Truseltiq, has shown promising results as an adjuvant therapy in patients with invasive urothelial carcinoma and FGFR3 alterations, as seen in the PROOF 302 study.

The role of FGFR3 alterations has come to light, revealing their potential as significant biomarkers for patient stratification and targeted therapies.

While infigratinib is proving its potential, other drugs like pembrolizumab continue to offer alternatives, contributing to a comprehensive arsenal of options for managing this form of cancer. Another compound, futibatinib, carries its own side effect profile that must be understood to ensure the safety of patients.

By bringing these insights together, we've attempted to give you a well-rounded view of the evolving landscape of urothelial carcinoma treatment.

As we continue to move forward, it's the wisdom of experts like Dr. Petros Grivas and many others that will continue to light our way, guiding us towards more effective, personalized treatments and, ultimately, better outcomes for patients.

Infigratinib: A Game Changer in Urothelial Carcinoma Therapy

Explore the breakthroughs in urothelial carcinoma treatment with infigratinib. From FDA approval to its role in targeted therapies, dive into this comprehensive guide.

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