Non-clear cell renal cell carcinoma (RCC) accounts for about 25% of all RCC diagnoses and usually has worse outcomes than clear cell RCC. Both cabozantinib and immune checkpoint inhibitors have shown preliminary activity in non-clear cell RCC. Cabozantinib appears to enhance the response to immune checkpoint inhibitors and has shown encouraging results in combination with immune checkpoint inhibitors in various tumour types, such as clear cell RCC, urothelial carcinoma, metastatic prostate cancer, and hepatocellular carcinoma.

At the European Society of Medical Oncology (ESMO) Virtual Congress 2020, initial results from COSMIC-021, a multi-centre phase 1b study, investigating the combination of cabozantinib with atezolizumab in various solid tumours were presented by Dr Bradley McGregor from the Dana-Farber Cancer Institute in Boston, USA .

The primary endpoint was objective response rate, and others included safety, duration of response, progression-free survival and overall survival. Tumours were assessed by CT or MRI at screening and every six weeks for the first 12 months and every 12 weeks thereafter.

Thirty (30) patients were enrolled with a median follow-up of 13.0 months. Sixteen (16) patients (53%) remained on treatment. There were 15 papillary, 7 chromophobe and 8 other non-clear cell subtypes.

Overall response rate was 33% and there were 10 patients with partial responses. There were no complete responses and disease control rate was 93%. Median duration of response was 7.9 months and median progression-free survival was 9.5 months.

Thirty percent of patients had severe or life-threatening adverse events and there were no deaths. Low levels of phosphate in the blood (hypophosphataemia) was the most common severe/life-threatening treatment-related adverse event (n=4, 13%).

In conclusion, cabozantinib plus atezolizumab demonstrated encouraging clinical activity in patients with non-clear cell RCC with an acceptable safety profile. Responses were seen across several subtypes of non-clear cell RCC and anti-tumour immune effects were seen in peripheral blood with cabozantinib plus atezolizumab. Further trials are ongoing with this combination of treatments in the second-line after immune checkpoint inhibitors, including patients with papillary or unclassified non-clear cell RCC.

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