Cabozantinib combined with O drug for advanced renal cell carcinoma

Cabozantinib combined with O drug in the treatment of advanced renal cell carcinoma.  The approval of the combination of Cabozantinib and the “O drug” for the treatment of advanced renal cancer is great news for such patients.

Recently, the US FDA approved Cabozantinib (Cabometyx) in combination with “O drug” nivolumab as the first-line treatment for patients with advanced renal cell carcinoma.

This is currently the only combination therapy that can double both PFS and ORR compared to sunitinib, while significantly improving OS in patients with advanced RCC. And it took less than 5 months from the submission of the application to the approval, one month earlier than the scheduled date, which is a milestone for such patients.

▌Advanced renal cell carcinoma

The American Cancer Society lists renal cancer (RCC) as one of the ten most common cancers in the United States. Clear cell RCC is the most common type of kidney cancer in adults.

If RCC can be detected at an early stage, the five-year survival rate is very high; however, most patients in clinical practice are already at an advanced stage when the cancer is diagnosed, and the five-year survival rate is only 12%. In 2020, there will be approximately 71,000 patients with advanced kidney cancer in the world who need systemic treatment.

Clear cell carcinoma accounts for about 70% of all RCCs. In most clear cell carcinomas, there is a protein called von Hippel-Lindau, whose levels are lower than normal, leading to increased levels of MET, AXL, and VEGF. These proteins promote tumor angiogenesis, growth, invasiveness and metastasis. MET and AXL may drive tumors to develop resistance to VEGF receptor inhibitors.

▌Cabotinib: the “magic oil” in anticancer drugs

Cabozantinib (trade name: Cabometyx) is a multi-target small molecule tyrosine kinase inhibitor, including MET, VEGFR12 3, ROS1, RET, AXL, NTRK, KIT nine targets. It mainly exerts anti-tumor effects by targeting the inhibition of MET, VEGFR2 and RET signaling pathways, killing tumor cells, reducing metastasis and inhibiting angiogenesis.

Because of its multiple targets, wide effects, and effectiveness on a variety of tumors, some people call cabozantinib the “magazine” in targeted drugs, which has broad-spectrum anticancer capabilities.

As an “old drug” that has been on the market for 8 years in the United States, cabozantinib is currently approved for the treatment of medullary thyroid cancer, renal cell carcinoma and liver cancer, as well as lung cancer, urothelial cancer, breast cancer, and ovarian cancer. Solid tumors such as colon cancer and other solid tumors show good survival benefits, and the effect of controlling bone metastasis is particularly outstanding.

Prior to this, nivolumab and cabozantinib were approved to treat renal cell carcinoma. As early as 2017, Cabozantinib was approved for use in untreated patients with advanced RCC. In April 2018, nivolumab combined with “Y drug” ipilimumab was also approved by the FDA for the first-line treatment of patients with advanced RCC with medium and high risk.

▌PFS and ORR doubled! Clinical data is amazing

This approval is based on the results of the Phase 3 CheckMate -9ER clinical trial.

The study enrolled 651 patients (25% PD-L1 ≥ 1%), and aimed to evaluate the combination of 40 mg cabozantinib and 240 mg nivolumab for the treatment of advanced or metastatic patients who have not received previous treatment Efficacy and safety of RCC patients. The primary endpoint is PFS, and secondary endpoints include OS and ORR.

The detailed data was announced at the virtual meeting of the European Society of Medical Oncology (ESMO·2020) held in September 2020.

The results show that:

At a median follow-up time of 18.1 months, compared with the sunitinib group, the median progression-free survival (PFS) of patients in the cabozantinib + nivolumab treatment group doubled (16.6 months VS 8.3 months), the primary endpoint was reached.

In addition, the objective response rate (ORR) of the cabozantinib + nivolumab treatment group also doubled, with an ORR of 56%, while the sunitinib group was 27%. At the same time, the combined treatment group significantly improved the overall survival of patients.

In addition, the trial reached the exploratory endpoint of health-related quality of life (HRQoL). In terms of safety, cabozantinib + nivolumab is well tolerated, and the safety is consistent with the results of previous first-line therapy.

The targeted immunotherapy combination of cabozantinib and nivolumab has doubled the progression-free median survival and objective remission rate of patients with renal cell carcinoma, while also significantly improving overall survival, which is expected to become a new diagnosis A new standard of first-line treatment for patients with renal cell carcinoma.

Unfortunately, cabozantinib has not yet been approved for marketing in some countries.

In this regard, patients should not rashly try some new drugs and new therapies that have not yet been marketed, or should follow the doctor’s advice.

(source:internet, reference only)

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