Results of a new study showed that the combination of Cabometyx (cabozantinib) and the immune checkpoint inhibitor Tecentriq (atezolizumab) was safe and effective in men with metastatic (spreading) castration-resistant prostate cancer, the most common type of prostate cancer. The results of the study were presented by Neeraj Agarwal, MD, Director, Genitourinary Oncology Program, Huntsman Cancer Institute, University of Utah, Salt Lake City, at the 2020 ASCO annual meeting. The men in the study also demonstrated long-lasting responses to the drug combination.
Metastatic castration-resistant prostate cancer can continue to progress and get worse even when drugs or other treatments that lower the amount of the male sex hormones are being used in the attempt to control the spread of the cancer. In previous studies of patients with other types of cancer, cabozantinib has demonstrated promising activity when given in combination with an immune checkpoint inhibitor, such as atezolizumab.
“The combination of cabozantinib and atezolizumab demonstrated a tolerable safety profile and clinically meaningful activity in men with metastatic castrate-resistant prostate cancer,” said Dr. Agarwal.
“Given the encouraging activity in these patients, especially in those with high-risk disease, further evaluation of cabozantinib and atezolizumab in men with metastatic castration-resistant prostate cancer is being pursued,” he added.
The multi-national study, called COSMIC-021, enrolled 130 men who had disease progression in their soft tissue as seen on radiographic images done after they received treatment with other drugs used for prostate cancer, Xtandi (enzalutamide) and/or Zytiga (abiraterone).
To be eligible for the study, the men were required to have measurable disease (a tumor that can be accurately measured in size), and an ECOG performance status of 0 or 1. ECOG performance status describes a patient’s level of functioning in terms of daily activities, ability to take care of themselves, and physical ability. A score of 0 or 1 translates to good functioning.
Most patients had high-risk disease, about one-quarter (25%) had previously received treatment with docetaxel (a type of chemotherapy), and about half had already received hormonal therapy, a common therapy used for prostate cancer.
Patients in the study received cabozantinib by mouth once daily, and atezolizumab every 3 weeks as an intravenous infusion. Dr. Agarwal presented the results from the first 44 patients who were enrolled in the study.
After an average follow-up of almost 16 months, the objective response (some response to therapy) rate among all 44 patients was 32%; 2 patients had a complete response (no sign of cancer) to therapy and 12 patients had a partial response to treatment with this combination, meaning that the tumor shrank but did not disappear completely.
The objective response rate in the 36 patients with high-risk disease was 33%, whereas 48% of patients reached stable disease with the combination therapy, and the disease control rate was 80% in all 44 patients; this percentage includes patients who had complete response, partial response, and stable disease. The responses were also long-lasting, with an average duration of slightly more than 8 months.
Any reduction in tumor lesions was observed in 73% of the patients, Dr. Agarwal said.
According to Dr. Agarwal, further evaluation of the combination of cabozantinib and atezolizumab for the treatment of patients with metastatic castration-resistant prostate cancer is planned in an upcoming phase 3 clinical trial.
Clinical trials are designed to test the safety and effectiveness of new drugs, and phase 3 clinical trials are typically the last step before FDA approval, with a focus on the safety of the drug. Once approved, these drugs expand the treatment options available for patients with cancer.
The investigators found the combination of cabozantinib and atezolizumab to have acceptable side effects. However, 59% of patients had frequent treatment-related serious (grade 3) or life-threatening (grade 4) side effects.
The most common grade 3 or 4 side effects were fatigue, diarrhea, and hyponatremia, low level of sodium in the blood.
In addition, 1 patient died during the study; this was a 90-year-old man who died of treatment-related dehydration.