Neeraj Agarwal, MD

Neeraj Agarwal, MD, professor of medicine, and director of the Genitourinary Oncology Program, Huntsman Cancer Institute, discusses the safety profile of olaparib (Lynparza) in homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC). 

 for the treatment of adult patients with deleterious or suspected deleterious germline or somatic HRR gene-mutated mCRPC who have progressed following treatment with enzalutamide (Xtandi) or abiraterone acetate (Zytiga). 

The approval is based on findings from the phase 3 PROfound trial, which demonstrated a 66% reduction in the risk of disease progression or death with olaparib compared with enzalutamide or abiraterone.

The safety of olaparib was consistent with previous data. Anemia, nausea, and fatigue were more commonly observed among patients treated with olaparib versus enzalutamide or abiraterone.

Nausea and anemia are manageable toxicities, says Agarwal. Additionally, the increased rate of fatigue is likely due to the increased rate of anemia.

Patients with HRR gene-mutant mCRPC have limited treatment options, explains Agarwal. Also, available chemotherapy regimens are associated with increased toxicity compared with olaparib. 

As such, the agent offers a novel, well-tolerated options for patients in this setting, Agarwal concludes.

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Neeraj Agarwal, MD, discusses the safety profile of olaparib in homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer.  


Dr. Agarwal on the Safety Profile of Olaparib in HRR Gene-Mutant mCRPC 

Neeraj Agarwal, MD, professor of medicine, and director of the Genitourinary Oncology Program, Huntsman Cancer Institute, discusses the rationale for the expansion of cohort 6 in the COSMIC-021 trial in metastatic castration-resistant prostate cancer (mCRPC).

The multicenter, open-label, phase 1b trial tested the combination of cabozantinib (Cabometyx) and atezolizumab (Tecentriq) in a wide variety of patient populations, says Agarwal. Based on encouraging efficacy and safety data, cohort 6, which consisted of patients with mCRPC, was expanded to a total of 130 patients. At this point, a large phase 3 trial had been planned.

The phase 3 trial will accrue patients all over the globe, including the United States. This study will further evaluate the combination of cabozantinib and atezolizumab in patients mCRPC, Agarwal concludes.

Neeraj Agarwal, MD, discusses the rationale for the expansion of cohort 6 in the COSMIC-021 trial in metastatic castration-resistant prostate cancer.

Dr. Agarwal on the Progression of the COSMIC-021 Trial in mCRPC

Neeraj Agarwal, MD, professor of medicine, and director of the Genitourinary Oncology Program, Huntsman Cancer Institute, discusses the results from the cohort 6 analysis of the COSMIC-021 trial in patients with metastatic castration-resistant prostate cancer​ (mCRPC).

Cohort 6 was one of the original cohorts in the COSMIC-021 trial Eligible patients had to have progressive soft tissue disease, ​but not necessarily prostate-specific antigen progression, says Agarwal. Men with mCRPC often experience aggressive disease.

After seeing encouraging efficacy data, cohort 6 was expanded to include 130 patients, ​explains Agarwal.

At the 2020 ASCO Virtual Scientific Program, an overall response rate of 32% was observed with the combination of cabozantinib (Cabometyx)* and atezolizumab ​(Tecentriq) in 44 men with mCRPC, Agarwal explains. Additionally, 48% of patients experienced stable disease.* The disease control rate was 80%. The median duration of objective response was 8.3 months, Agarwal adds. These data appear* promising. The combination is being evaluated in a​n international phase 3 trial. 


Neeraj Agarwal, MD, discusses the results from the cohort 6 analysis of the COSMIC-021 trial in patients with metastatic castration-resistant prostate cancer​.

Dr. Agarwal on Cohort 6 Results ​From the COSMIC-021 Trial in mCRPC

Neeraj Agarwal, MD, professor of medicine, and director of the Genitourinary Oncology Program, Huntsman Cancer Institute, discusses the rationale for novel combination therapies in metastatic castration-resistant prostate cancer​ (mCRPC).

Oftentimes, patients with mCRPC experience disease progression on hormonal therapies, such as abiraterone acetate (Zytiga) or enzalutamide (Xtandi), says Agarw​al.

At the 2020 ASCO Virtual Scientific Program, findings from a large, real-world study of over 1000 patients were presented, which was obtained from Flatiron Health, Agarwal explains. Although these data were not surprising, they confirm that noveltreatment options need to be available for this patient population, Agarwal adds.

The overall survival ​(OS) after first-line abiraterone was 15​.7 months with enzalutamide ​compared with 9.4 months with docetaxel. The OS after first-line enzalutamide was 13.3 months with abiraterone versus 9.7 months with docetaxel. These data show that this is an area of high unmet need.

To that end, the​ phase 1b COSMIC-021 trial is evaluating the combination of cabozantinib (Cabometyx) and atezolizumab (Tecentriq) in patients with mCRPC, Agarwal concludes.

Neeraj Agarwal, MD, discusses the rationale for novel combination therapies in metastatic castration-resistant prostate cancer​. 

Author | Neeraj Agarwal, MD

Articles

Dr. Agarwal on the Safety Profile of Olaparib in HRR Gene-Mutant mCRPC

Dr. Agarwal on the Progression of the COSMIC-021 Trial in mCRPC

Dr. Agarwal on Cohort 6 Results From the COSMIC-021 Trial in mCRPC

Dr Agarwal on the Rationale for Novel Combination Therapies in mCRPC

Author | Neeraj Agarwal, MD

Articles

Dr. Agarwal on the Safety Profile of Olaparib in HRR Gene-Mutant mCRPC

Dr. Agarwal on the Progression of the COSMIC-021 Trial in mCRPC

Dr. Agarwal on Cohort 6 Results ​From the COSMIC-021 Trial in mCRPC

Dr Agarwal on the Rationale for ​Novel Combination​ ​Therapies in ​mCRPC

Dr. Agarwal on Cohort 6 Results From the COSMIC-021 Trial in mCRPC

Dr Agarwal on the Rationale for Novel Combination Therapies in mCRPC