Michael Schweizer, MD, a physician of the Seattle Cancer Care Alliance, assistant professor in the Division of Medical Oncology at the University of Washington School of Medicine, and associate professor in the Clinical Research Division at the Fred Hutchinson Cancer Research Center, discusses the results of the HERO trial in prostate cancer.

In the pivotal, phase 3 HERO trial, 934 patients with androgen-sensitive advanced prostate cancer were randomized 2:1 to receive 120 mg of oral relugolix (Orgovyx) once daily after a one-time 360 mg loading dose of relugolix or a 3-month depot injection of leuprolide (Lupron). 

 The results showed that 96.7% (95% CI, 94.9%-97.9%) of men treated with relugolix achieved and maintained castration through 48 weeks compared with 88.8% (95% CI, 84.6% to 91.8%) with leuprolide, translating to an absolute difference of 7.9% (95% CI, 4.1%-11.8%). As such, relugolix demonstrated noninferiority and superiority (

 < 0.0001) versus leuprolide. Notably, all key secondary end points favored relugolix versus leuprolide (

 < 0.0001) and patients had rapid recoveries of testosterone, Schweizer says. 

Although relugolix was associated with lower rates of major adverse cardiovascular events compared with leuprolide, the safety and tolerability profiles of the 2 agents were similar. Common adverse events for patients treated with relugolix or leuprolide were hot flash (54.3% vs 51.6%, respectively), fatigue (21.5% vs 18.5%), constipation (12.2% vs 9.7%), diarrhea (12.2% vs 6.8%), arthralgia (12.1% vs 9.1%), and hypertension (7.9% vs 11.7%), Schweizer concludes. 

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Michael Schweizer, MD, discusses the results of the HERO trial in prostate cancer. 
  


Dr. Schweizer on the Results of the HERO Trial in Prostate Cancer 

Michael Schweizer, MD, a physician of the Seattle Cancer Care Alliance, assistant professor in the Division of Medical Oncology at the University of Washington School of Medicine, and associate professor in the Clinical Research Division of the Fred Hutchinson Cancer Research Center, discusses the rationale for the phase 3 CARD trial in metastatic castration-resistant prostate cancer (mCRPC). 

The CARD trial randomized men with mCRPC to receive either cabazitaxel (Jevtana), or abiraterone acetate (Zytiga) or enzalutamide (Xtandi), depending on which androgen signaling inhibitor patients had received previously.

Retrospective analyses have suggested that when drugs like abiraterone or enzalutamide are used sequentially, the second used is not as effective, Schweizer says. Antiandrogens have similar mechanisms of action and work to shut down the androgen receptor–signaling pathway. As such, cross resistance and diminished clinical activity are likely results of sequentially use, Schweizer explains. 

The CARD trial was designed in response to these findings; investigators evaluated whether cabazitaxel could replace a second antiandrogen in patients who had progressed on abiraterone or enzalutamide, concludes Schweizer. 

Michael Schweizer, MD, discusses the rationale for the phase 3 CARD trial in metastatic castration-resistant prostate cancer.  



Dr. Schweizer on the Rationale for the CARD Trial in mCRPC 

Michael Schweizer, MD, physician, Seattle Cancer Care Alliance, assistant professor, Division of Medical Oncology, University of Washington School of Medicine, associate professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, discusses the role of olaparib (Lynparza) in patients with non–

-mutant metastatic castration-resistant prostate cancer (mCRPC).

The phase 3 PROfound trial demonstrated prolonged progression-free survival (PFS) with the PARP inhibitor olaparib in men with mCRPC who had disease progression on enzalutamide (Xtandi) or abiraterone acetate (Zytiga). Cohort A consisted of patients with at least 1 alteration in 

, and cohort B comprised patients with at least one alteration in any of the other 12 prespecified genes. 

Although olaparib demonstrated a significant radiographic PFS benefit in the overall patient population and in cohort A, radiographic PFS findings for cohort B did not show a significant benefit with olaparib vs the control regimen for patients with non–

Although the trial was not powered to analyze differences in radiographic PFS between specific genetic mutations, these data highlight the need for additional research to determine whether olaparib should be considered for patients with mCRPC who lack 

 mutations, Schweizer says. As it stands, olaparib can be utilized for these patients; however, more standard options that have demonstrated efficacy across genomic subtypes should be preferred, concludes Schweizer.

Michael Schweizer, MD, discusses the role of olaparib in patients with non–BRCA-mutant metastatic castration-resistant prostate cancer.  


Michael Schweizer, MD

Articles

Dr. Schweizer on the Results of the HERO Trial in Prostate Cancer

Dr. Schweizer on the Rationale for the CARD Trial in mCRPC

Dr. Schweizer on the Role of Olaparib in Non–BRCA-Mutant mCRPC