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ESMO 2019: Dr. McGregor Highlights Impactful 2019 Prostate Cancer Studies

Bradley McGregor, MD
Published: Friday, Oct 18, 2019



Bradley McGregor, MD, clinical director, Lank Center for Genitourinary Oncology, senior physician, Dana-Farber Cancer Institute, and instructor of medicine, Harvard Medical School, discusses the most impactful trials in prostate cancer presented at the 2019 ESMO Congress. 
 
In the era of personalized precision medicine, results from the phase III PROfound trial and the phase II GALAHAD study are encouraging for targeted therapy in prostate cancer, says McGregor.
 
The PROfound trial compared olaparib (Lynparza) with physician’s choice of enzalutamide (Xtandi) or abiraterone acetate (Zytiga) in patients with heavily pretreated, metastatic castration-resistant prostate cancer (mCRPC) who harbor homologous recombination repair (HRR) gene alterations. Notably, up to 30% of patients with mCRPC harbor DNA damage repair alterations. In the trial, olaparib was found to improve radiographic progression-free survival (rPFS) compared with enzalutamide or abiraterone. The median rPFS for patients with BRCA1/2 or ATM alterations (cohort A) was 7.39 months versus 3.55 months for patients treated with hormonal therapy (HR, 0.34; P <.0001). A slight trend was reported for benefit in patients with an alteration in BARD1, BRIP1, CDK12, CHEK1/2, FANCL, PALB2, PPP2R2A, RAD51B/C/D, or RAD54L (cohort B), but it was not statistically significant for rPFS (HR, 0.88). 
 
Interim analysis of the GALAHAD trial, investigating single-agent niraparib (Zejula), also demonstrated encouraging activity in patients with mCRPC. Specifically, among patients with BRCA-mutated biallelic DNA-repair gene defects. The objective response rate for patients with biallelic BRCA1/2 mutations was 41% compared with 9% for patients with non-BRCA biallelic DRD. Although the trial is ongoing, these data suggest a potential role for niraparib monotherapy in this patient population, says McGregor. 
 
Chemotherapy still plays a role in prostate cancer as demonstrated by the randomized CARD trial comparing cabazitaxel (Jevtana) with enzalutamide or abiraterone in men with mCRPC, says McGregor. Overall survival (OS) was 13.6 months with cabazitaxel versus 11.0 months with enzalutamide or abiraterone (HR, 0.64; 95% CI, 0.46-0.89; P =.008). Time to progression was more than doubled with cabazitaxel at 8.0 months versus 3.7 months with either androgen signaling inhibitor. These data demonstrate the importance of chemotherapy in later-line settings for patients who progress on hormonal therapy. 
                                                    
Finally, an updated analysis of the phase III SPARTAN trial showed an improvement in metastasis-free survival (MFS) with the addition of apalutamide (Erleada) to androgen-deprivation therapy for men with nonmetastatic CRPC. Median MFS was 40.5 months for patients treated with apalutamide compared with 16.2 months with placebo (HR, 0.28; 95% CI, 0.23-0.35; P <.0001). OS has not yet been reached, says McGregor, but there is a trend toward improvement with apalutamide. Although the P value wasn’t statistically significant, the data are clinically significant, says McGregor. 
 
The field of prostate cancer is rapidly evolving, McGregor concludes. Going forward, additional biomarkers and novel targeted agents may lead to further disease control and more durable responses. 
 
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Bradley McGregor, MD, clinical director, Lank Center for Genitourinary Oncology, senior physician, Dana-Farber Cancer Institute, and instructor of medicine, Harvard Medical School, discusses the most impactful trials in prostate cancer presented at the 2019 ESMO Congress. 
 
In the era of personalized precision medicine, results from the phase III PROfound trial and the phase II GALAHAD study are encouraging for targeted therapy in prostate cancer, says McGregor.
 
The PROfound trial compared olaparib (Lynparza) with physician’s choice of enzalutamide (Xtandi) or abiraterone acetate (Zytiga) in patients with heavily pretreated, metastatic castration-resistant prostate cancer (mCRPC) who harbor homologous recombination repair (HRR) gene alterations. Notably, up to 30% of patients with mCRPC harbor DNA damage repair alterations. In the trial, olaparib was found to improve radiographic progression-free survival (rPFS) compared with enzalutamide or abiraterone. The median rPFS for patients with BRCA1/2 or ATM alterations (cohort A) was 7.39 months versus 3.55 months for patients treated with hormonal therapy (HR, 0.34; P <.0001). A slight trend was reported for benefit in patients with an alteration in BARD1, BRIP1, CDK12, CHEK1/2, FANCL, PALB2, PPP2R2A, RAD51B/C/D, or RAD54L (cohort B), but it was not statistically significant for rPFS (HR, 0.88). 
 
Interim analysis of the GALAHAD trial, investigating single-agent niraparib (Zejula), also demonstrated encouraging activity in patients with mCRPC. Specifically, among patients with BRCA-mutated biallelic DNA-repair gene defects. The objective response rate for patients with biallelic BRCA1/2 mutations was 41% compared with 9% for patients with non-BRCA biallelic DRD. Although the trial is ongoing, these data suggest a potential role for niraparib monotherapy in this patient population, says McGregor. 
 
Chemotherapy still plays a role in prostate cancer as demonstrated by the randomized CARD trial comparing cabazitaxel (Jevtana) with enzalutamide or abiraterone in men with mCRPC, says McGregor. Overall survival (OS) was 13.6 months with cabazitaxel versus 11.0 months with enzalutamide or abiraterone (HR, 0.64; 95% CI, 0.46-0.89; P =.008). Time to progression was more than doubled with cabazitaxel at 8.0 months versus 3.7 months with either androgen signaling inhibitor. These data demonstrate the importance of chemotherapy in later-line settings for patients who progress on hormonal therapy. 
                                                    
Finally, an updated analysis of the phase III SPARTAN trial showed an improvement in metastasis-free survival (MFS) with the addition of apalutamide (Erleada) to androgen-deprivation therapy for men with nonmetastatic CRPC. Median MFS was 40.5 months for patients treated with apalutamide compared with 16.2 months with placebo (HR, 0.28; 95% CI, 0.23-0.35; P <.0001). OS has not yet been reached, says McGregor, but there is a trend toward improvement with apalutamide. Although the P value wasn’t statistically significant, the data are clinically significant, says McGregor. 
 
The field of prostate cancer is rapidly evolving, McGregor concludes. Going forward, additional biomarkers and novel targeted agents may lead to further disease control and more durable responses. 
 
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