The efficacy data of Erdafitinib has been released, and the price difference between domestic and foreign countries is huge. How should patients choose?

1. The latest hot spots: new breakthroughs in precision treatment of bladder cancer

Bladder cancer is one of the most common malignant tumors of the urinary system, especially among men. According to data released by the International Agency for Research on Cancer (IARC) 2022, there are more than 57 new patients with bladder cancer and more than 21 deaths every year worldwide. The incidence of bladder cancer in my country is increasing year by year, and most patients are already in the mid-to-late stage when diagnosed, making treatment difficult and the recurrence rate high.

Traditionally, advanced bladder cancer mainly relies on chemotherapy or immunotherapy, but the overall response rate is unsatisfactory and most patients have limited survival. In recent years, with the development of genetic testing technology, scientists have discovered that some patients with bladder cancer have FGFR2 or FGFR3 gene mutation/fusion. These patients have poor response to conventional chemotherapy and immunotherapy, but can obtain curative effects by targeting the FGFR pathway.

In this context, Erdafitinib (Erdafitinib) became the world's first oral drug approved for the treatment of FGFR gene-abnormal bladder cancer, quickly attracting widespread attention from the medical community and patients. In 2023, the State Food and Drug Administration (NMPA) approved the marketing of erdafitinib in China, bringing a new treatment option to Chinese patients and making "bladder cancer precision medicine" a new hot topic.

2. What is erdafitinib? Analysis of mechanism of action and indications

Erdafitinib is a pan-FGFR tyrosine kinase inhibitor developed by Johnson & Johnson, which can specifically inhibit the abnormal activity of FGFR1-4.

1.FGFRMutation and Cancer

FGFR (Fibroblast growth factor receptor) family plays an important role in cell differentiation, angiogenesis, and tissue repair. However, in some tumors, the FGFR2 or FGFR3 genes are mutated or fused, resulting in continuous activation of signaling pathways and promoting unlimited proliferation of cancer cells. The incidence of FGFR3 mutations in bladder cancer is as high as more than 20%.

2.Mechanism of action

Erdafitinib inhibits the growth, angiogenesis and metastasis of tumor cells by inhibiting FGFR kinase activity and blocking signal transduction.

3.Approved indications

FDA(2019): Treatment existsFGFR2or Patients with locally advanced or metastatic urothelial carcinoma (bladder cancer) who have span>FGFR3mutations/fusion and have previously received platinum-based chemotherapy.

ChinaNMPA (2023): Approved erdafitinib for marketing in China, and the indications are basically the same as FDA.

This approval marks a major advance in the precision treatment of bladder cancer, allowing some patients with genetic mutations to have specialized targeted treatment options for the first time.

3. Clinical efficacy data: new hope brought by erdafitinib

1. BLC2001Key Research

This was the core trial supporting the approval of erdafitinib, and the results were published in the New England Journal of Medicine.

Enrolled subjects:99casesFGFR2/3bladder cancer patients with mutations or fusions

Treatment plan: Oral erdafitinib8mg/day (adjusted according to serum phosphorus level)

Key results:

Objective response rate (ORR): 40%

Disease control rate (DCR): 72%

Median progression-free survival (PFS): 5.5months

Median overall survival (OS): 13.8months

This result is much higher than that of second-line chemotherapy (ORR is only about 10%), showing a significant advantage.

2. Long-term follow-up results

After treatment with erdafitinib, some patients experienced a significant reduction in tumor burden and maintained remission for more than one year, demonstrating the durability of its efficacy.

3. Comparison with immunotherapy

In patients who are ineffective in immunotherapy, erdafitinib shows a higher response rate, providing patients with a new option. Especially for patients who are resistant to PD-1/PD-L1 inhibitors, erdafitinib is an ideal alternative.

4. Side effects and safety: How to deal with them?

Erdafitinib is generally safe and controllable, but adverse reactions still require attention:

1.Hyperphosphatemia (occurring in approximately 77% of patients): drug mechanism is related and can be treated through dietary control and phosphorus-lowering drugs.

2.Ocular adverse reactions: such as central serous retinopathy (CSR), so patients are advised to have regular eye examinations.

3.Other common side effects: stomatitis, rash, fatigue, dry eye syndrome, nail bed changes, etc.

4.Clinical recommendations:

Detect genetic mutations before treatment to ensure indications.

Monitor serum phosphorus levels regularly.

If blurred vision occurs, the medication must be stopped immediately and medical attention must be sought.

In general, the vast majority of adverse reactions can be alleviated through dose adjustment or symptomatic treatment and will not lead to large-scale discontinuation of treatment.

5. Price analysis: obvious differences between domestic and foreign countries

Although the efficacy is good, price has become one of the biggest concerns for patients.

1. Domestic price situation

Erdafitinib has been on the market for a short time in the country and is not yet included in medical insurance.

Due to limited channels, it is difficult to purchase drugs directly from domestic hospitals.

Patients purchase more through cross-border channels.

2. Hong Kong original drug

Mainly sold through regular pharmacies.

Price: About2more than RMB / boxes.

It is expensive and imposes a huge financial burden on patients undergoing long-term treatment.

3. Overseas generic drugs

Main version: Lao version of generic version.

Price range: 900Multiple/ boxes.

The ingredients are basically the same as the original drug, but the clinical verification data is relatively limited.

4. Reasons for price differences

R&D investment: Original drugs require more than ten years of R&D investment, which is very costly.

Patent protection: The original drug has market exclusivity.

Medical insurance policy: Domestic medical insurance is not included, and patients must pay the full amount out of their own pocket.

Differences in generic drug policies: Some countries have relaxed patent protection and accelerated the launch of generic drugs.

6. Frequently Asked Questions for Patients

1. How long does it take for erdafitinib to be effective?

Most patients can see tumor shrinkage or symptom improvement after taking the drug for 2–3 cycles (about 2–3 months).

2. Can all bladder cancer patients use it?

Not applicable. Only FGFR2/FGFR3 mutation or fusion-positive patients can benefit, and genetic testing must be done first.

3. Are generic drugs reliable?

The ingredients are basically the same, but there is a lack of large-scale clinical verification. It is recommended to purchase through regular channels under the guidance of a doctor.

4. Will relapse occur if the drug is stopped?

Some patients may experience disease progression after stopping the drug, so the course of treatment needs to be evaluated under the guidance of a doctor.

5. Is it possible to get medical insurance?

It is generally expected in the industry that as patient demand grows and negotiations progress, there will be opportunities to include it in medical insurance in the future to reduce the burden on patients.

Summary

Erdafitinib, as the world's first FGFR targeted drug, has filled the gap in precision treatment of bladder cancer and brought significant curative effects to patients with FGFR mutations. Its ORR in the BLC2001 study reached 40%, which is significantly better than traditional second-line chemotherapy and brings new hope for survival to patients.

However, the high price has become an important reason hindering its popularity. Although it has been launched in China, it has not yet been reimbursed by medical insurance; the price of overseas original drugs is high, and although generic drugs are cheap, there is a problem in selection. How to find a balance between efficacy, price, and safety is a problem that patients and the medical system need to face together.

The most important thing for patients is:

1. Carry out genetic testing in a timely manner to confirm whether you are suitable for medication;

2.Purchase drugs through formal channels to ensure safety;

3.Standardize treatment under the guidance of a doctor to improve efficacy and control side effects.

With the release of more clinical data and progress in medical insurance policies, the accessibility and popularity of erdafitinib in China is expected to gradually increase, bringing hope to more bladder cancer patients.

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References

1."New England Journal of Medicine":Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma

2.FDAOfficial website:FDA approves erdafitinib for locally advanced or metastatic urothelial carcinoma

3.ASCO & ESMO 2023–2024Conference Materials