Bladder cancer, also renowned with the name of urinary bladder cancer or urological cancer, is considered amongst the world's most common cancers and the incidences of this problematic cancer are still on the rise steadily, notably in developed countries.
According to the latest GLOBOCAN data, bladder cancer is accounting for about 3% of the global cancer diagnosis, with 550,000 new cases annually. Generally, 90% of the bladder cancer diagnosis found in the people with the age of 55 years or older and is four times common in males as a comparison to the females.
Radical cystectomy and cisplatin-based combination chemotherapy are the standards of care for bladder cancer treatment. Immunotherapy, Avelumab has also been approved recently as a maintenance therapy to treat various types of bladder cancer.
Other than these therapies, the targeted therapy has earned a significant place in the management of certain types of cancer in the past years because of its selective action against malignant cells. With the growing epoch of targeted therapies near the 2000s, many trials assessed the impact of this mode of treatment in the context of advanced bladder cancer. Thereafter, many trials aimed at the analysis of targeted therapy molecules in bladder cancer have been reviewed.
Recently, FDA has been approved erdafitinib as the first targeted therapy for treating advanced bladder cancer involving a mutation in fibroblast growth factor receptors 2 (FGFR 2) or FGFR 3 gene and patients who's condition got worse following the chemotherapy.
Let's explore little deep, What is targeted therapy and how erdafitinib as targeted therapy works to manage bladder cancer so efficiently?
- What is bladder cancer?
- What is targeted therapy?
- Role of FGFR inhibitors in bladder cancer treatment
- Erdafitinib as target therapy for bladder cancer
What is bladder cancer?
Bladder cancer is the 10th most common cancer around the globe, most often starts in the urothelial cells that line the inside of the bladder. Urothelial cells are also present in the kidneys and tube connects bladder and kidneys, however, urothelial cancer in the bladder is much more common.
Other than this, there are other types of bladder cancer are also there, for instance, squamous cell carcinoma (1-2%), adenocarcinoma (1%), small cell carcinoma (1%) and sarcoma (rare).
The bladder function is to store urine up to 400-600 ml and allowing controlled and infrequent urination. Bladder cancer can affect this function up to extreme levels and therefore, timely diagnosis and treatment to eradicate cancer from the roots is very important. In this, target therapy can become a milestone.
What is targeted therapy?
What exactly is the targeted therapy? It is a therapy in which the drugs are targeted to act against specific proteins and genes, which involved in cancer growth and survival. This therapy can substantially influence the tissue environment and turns off the signals that aids in cancer progression and metastasis.
As aforementioned, a recently approved drug, erdafitinib, an FGFR inhibitor for also acts in the same fashion. It used as a targeted therapy to treat bladder cancer safely and effectively.
Role of FGFR inhibitors in bladder cancer treatment
Fibroblast growth factor receptor (FGFR) is a form of protein, divided into various isoforms (FGFR1, FGFR2, FGFR3) which express differently in cell lines and tissues to conduct various roles. An inappropriate mutation or expression of these receptors is substantially associated with malignancies development.
The FGFR genes are activated in certain cancers as a result of coding mutation, gene amplification and two types gene fusion, which further significantly helps in various types of cancer development, such as, breast, gastric, bladder, and lung cancer.
Inhibitors of these receptors found to be an amazing management approach for a specific class of bladder cancer patients. In bladder cancer, it is the luminal-papillary subtype which is characterized by FGFR modifications.
Erdafitinib as target therapy for bladder cancer
According to the outcomes of phase 2 BLC2001 trial, Erdafitinib exhibited 40% an overall response rate against metastatic bladder cancer with FGFR mutations, with this, it is the first FDA approved targeted therapy for Locally advanced or metastatic bladder cancer. Let's discuss following points:
- Mechanism of action
- Dosage and administration
- Possible adverse events
- Warning & Precautions
- Drug Indications
1. Mechanism of action
Erdafitinib exhibits its action by inhibiting the FGFR phosphorylation and signalling, thereby reduces the cell viability in cell lines showing FGFR genetic alterations.
2. Dosage and administration
- Progressed in the course of or after at least one line before platinum-containing chemotherapy.
- Recommended initial dose: 8 mg one-time daily with a dosage enhanced to 9 mg daily, if the criteria are met.
- Consumed whole with or without food.
3. Possible adverse events
Common adverse reactions involve: Fatigue, stomatitis, decreased appetite, dry mouth, dysgeusia, dry skin, alopecia, constipation, abdominal pain, nausea or musculoskeletal pain.
No contraindications were found to be associated with erdafitinib.
5. Warning & Precautions
- Hyperphosphatemia (Increase in body phosphate levels)
- Embryo-fetal toxicity
- Ocular disorders (central serous retinopathy)
6. Drug Indications
Avoid concomitant use of erdafitinib with phosphate-level altering agents, strong CYP2C9 or CYP3A4 inducers, OCT2 substrates and P-gp substrates.
In course of advanced or metastatic bladder cancer treatment, erdafitinib as a targeted therapy has gained a lot of attention in the field of oncology due to its more precise treatment action and safety. The only advice FDA given to patients while taking this treatment is regular eye checkup, blood phosphate levels checkup and avoid its intake during pregnancy and breastfeeding.
You can also read more recently approved chemotherapeutic drugs for various cancers, like, pembrolizumab for colorectal cancer, Anastrozole for breast cancer and certain lifestyle modifications to lower the risk of various cancer.