Renal cell carcinoma (RCC) or kidney cancer, have evolved to be an area of extensive clinical research in optimization of treatment outcomes. Current ongoing phase II/III clinical trials in kidney cancer have been examined in detail, investigating pivotal pathways involved and new information emerging on patient populations being targeted as well as trends with therapies.
The following table provides an overview of the primary mechanisms of action targeted in kidney cancer trials, the key drugs involved.
|
Mechanism of Action |
Key Drugs |
|---|---|
|
Immune Checkpoint Inhibition |
Pembrolizumab, Nivolumab, Atezolizumab |
|
VEGF/VEGFR Inhibition (Angiogenesis Inhibition) |
Bevacizumab, Axitinib, Sunitinib |
|
Tyrosine Kinase Inhibition |
Cabozantinib, Pazopanib, Lenvatinib |
|
mTOR Pathway Inhibition |
Everolimus, Temsirolimus |
|
Combination Therapy (Immune Checkpoint + VEGF Inhibitors) |
Pembrolizumab + Axitinib, Avelumab + Axitinib |
|
HIF-2α Inhibition |
Belzutifan |
|
PARP Inhibition |
Olaparib, Niraparib |
Immune Checkpoint Inhibition (220 Trials): Such drugs that work by blocking a protein interaction called PD-1/PD-L1 enable our own immune systems to attack and kill cancer cells. This has changed the way that advanced kidney cancer is treated for ever.
VEGF/VEGFR Inhibition (190 Trials): Bevacizumab and Sunitinib, drugs that block the VEGF pathway necessary for blood vessel formation to tumors. This mechanism is of special importance in RCC, one the most vascularized malignancies.
Tyrosine Kinase Inhibition (170 Trials): Both Cabozantinib and Pazopanib target several pathways that are involved in cancer cell growth and spread, which is why they can offer a lot of clinical benefit (ie. because the inhibition would be more specific)
mTOR Pathway Inhibition (90 Trials): Everolimus and Temsirolimus are both inhibitors of the mTOR pathway, a common important contributor to kidney cancer that causes unrelenting cell growth and survival.
Combination Therapy (130 Trials): The combination of immune checkpoint inhibitors with VEGF blockade, such as Pembrolizumab plus Axitinib has shown improved response rates in RCC by combining the mechanism of action.
HIF-2α Inhibition (50 Trials): A first-in-class agent, belzutifan targets the HIF-2α protein that is essential for RCC to develop in hypoxic regions of tumors.
PARP Inhibition (40 Trials): Olaparib and Niraparib take advantage of these repair deficiencies in kidney cancer cells, making a way for the targeted therapy available to some metabolic subtypes
In the United States, kidney cancer is a public health challenge. It is estimated that in 2024, around 81,610 new cases of kidney and renal pelvis cancer will occur in the U.S., leading to about 14,390 deaths.
The cancer is higher in men and more likely to be diagnosed at twice the rate in women. RCC is responsible for 90% of all kidney cancer cases; the disease has an age at diagnosis peak around 65.
Among all types of cancer reported for kidney and renal parenchyma, the 5-year relative survival rate is estimated at 77.6%, with a great disparity depending on the extent to which it has been categorized as metastatic or non-metastatic disease (stages I-III had an overall survival. For the localized stages of kidney cancer, 5-year survival is93.3%, whereas for distant (metastatic) cases it's17.4%
Academic-led kidney cancer trials like these are expected to have a major impact on the standard of care, especially with increasing use of combination treatments and targeted agents. It is currently being explored whether newer agents such as HIF-2α inhibitors can be integrated to delve into the realm of personalized medicine for RCC. With the progress of clinical trials, they will have an impact on both regulatory decisions and market dynamics -- making it crucial to keep abreast of these developments.
1.1 Overview of Kidney Cancer
1.2 Importance of Clinical Trials in Kidney Cancer Research
2.1 Incidence and Prevalence
2.2 Demographic Distribution
2.3 Mortality Rates and Survival Statistics
3.1 Overview of Ongoing Clinical Trials
3.2 Geographical Distribution of Research Efforts
4.1 Immune Checkpoint Inhibition
4.2 VEGF/VEGFR Inhibition (Angiogenesis Inhibition)
4.3 Tyrosine Kinase Inhibition
4.4 mTOR Pathway Inhibition
4.5 Combination Therapy (Immune Checkpoint + VEGF Inhibitors)
4.6 HIF-2α Inhibition
4.7 PARP Inhibition
5.1 Phase-wise Distribution of Trials
5.2 Insights into Progression and Focus Across Different Phases
6.1 Potential New Standards of Care
6.2 Impact on Regulatory and Market Dynamics
7.1 Summary of Key Findings
7.2 Future Directions in Kidney Cancer Research
8.1 Glossary of Terms
8.2 List of Abbreviations
8.3 References and Data Sources
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