Late Breaking Abstract – ASCO 2021: PSMA Targeted Radioligand Therapy Improves Progression Free Survival and Overall Survival in Metastatic Prostate Cancer

SUMMARY: Prostate cancer is the most common cancer in American men with the exclusion of skin cancer, and 1 in 8 men will be diagnosed with prostate cancer during their lifetime. It is estimated that in the United States, about 248,530 new cases of prostate cancer will be diagnosed in 2021 and 34,130 men will die of the disease.

The development and progression of prostate cancer is driven by androgens. Androgen Deprivation Therapy (ADT) or testosterone suppression has therefore been the cornerstone of treatment of advanced prostate cancer, and is the first treatment intervention. Approximately 10-20% of patients with advanced Prostate cancer will progress to Castration Resistant Prostate Cancer (CRPC) within five years during ADT, and over 80% of these patients will have metastatic disease at the time of CRPC diagnosis. Among those patients without metastases at CRPC diagnosis, 33% are likely to develop metastases within two years. Progression to Castration Resistant Prostate Cancer (CRPC) often manifests itself with a rising PSA (Prostate Specific Antigen) and the estimated mean survival of patients with CRPC is 9-36 months, and there is therefore an unmet need for new effective therapies.

Prostate-Specific Membrane Antigen (PSMA) is a type II cell membrane glycoprotein that is selectively expressed in prostate cells, with higher levels of expression in prostatic adenocarcinoma. PSMA is a therefore an excellent target for molecular imaging and therapeutics, due to its high specificity for prostate cancer.

Lu-177-PSMA-617 is a radiopharmaceutical that targets PSMA. It is comprised of Lutetium-177, linked to the ligand PSMA-617, a small molecule designed to bind with high affinity to PSMA. Radioligand therapy with Lu-177-PSMA-617 targets PSMA and releases its payload of lethal beta radiation into the prostate cancer cell. The antitumor activity and safety of Lu-177-PSMA-617 have been established previously in a Phase II study (Lancet Oncol. 2018;19:825-833).

VISION is an international, randomized, open-label Phase III study in which the benefit of Lu-177-PSMA-617 was evaluated in men with PSMA-positive mCRPC, previously treated with second generation Androgen Receptor signaling pathway inhibitor (XTANDI®-Enzalutamide or ZYTIGA®-Abiraterone acetate), and 1-2 taxane chemotherapy regimens. In this trial, 831 patients were randomized 2:1 to receive Lu-177-PSMA-617, 7.4 GBq every 6 weeks for 6 cycles plus Standard of Care as determined by the treating physician (N=551), or Standard of Care only (N=280). Both treatment groups were well balanced and this trial excluded patients treated with XOFIGO® (Radium-223). Enrolled patients had a castrate level or serum/plasma testosterone of lower than 50 ng/dL, and PET imaging with 68Ga-PSMA-11 was used to determine PSMA positivity by central review. The Primary endpoints were radiographic Progression Free Survival (rPFS) by Independent Central Review (ICR) and Overall Survival (OS). Secondary endpoints included Objective Response Rate (ORR), Disease Control Rate (DCR), and time to first Symptomatic Skeletal Event (SSE). The median study follow up was 20.9 months.

Lu-177-PSMA-617 plus Standard of Care significantly improved rPFS by 60%, compared to Standard of Care alone (median rPFS 8.7 versus 3.4 months, HR=0.40; P<0.001). The median OS was also significantly improved by 38% with Lu-177-PSMA-617 plus Standard of Care compared to Standard of Care alone (median OS 15.3 versus 11.3 months, HR=0.62; P<0.001). All key secondary endpoints including Objective Response Rate, Disease Control Rate, and time to first Symptomatic Skeletal Event were statistically significant, and in favor of Lu-177-PSMA-617 plus Standard of Care.

It was concluded that radioligand therapy with Lutetium-177–PSMA-617 significantly improved radiographic Progression Free Survival and Overall Survival when added to Standard of Care, compared with Standard of Care alone, in men with PSMA-positive metastatic Castration Resistant Prostate Cancer.

Phase 3 study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION). Morris MJ, De Bono JS, Chi KN, et al. J Clin Oncol. 2021;39(suppl 15):LBA4.

Final Analysis Confirms Superior OS Benefit with ERLEADA® in Metastatic Castrate Sensitive Prostate Cancer

SUMMARY: Prostate cancer is the most common cancer in American men with the exclusion of skin cancer, and 1 in 8 men will be diagnosed with prostate cancer during their lifetime. It is estimated that in the United States, about 248,530 new cases of prostate cancer will be diagnosed in 2021 and 34,130 men will die of the disease. The development and progression of prostate cancer is driven by androgens. Androgen Deprivation Therapy (ADT) or testosterone suppression has therefore been the cornerstone of treatment of advanced prostate cancer, and is the first treatment intervention. Androgen Deprivation Therapies have included bilateral orchiectomy or Gonadotropin Releasing Hormone (GnRH) analogues, with or without first generation Androgen Receptor (AR) inhibitors such as CASODEX® (Bicalutamide), NILANDRON® (Nilutamide) and EULEXIN® (Flutamide) or with second generation anti-androgen agents, which include ZYTIGA® (Abiraterone), XTANDI® (Enzalutamide), ERLEADA® (Apalutamide) and NUBEQA® (Darolutamide). Approximately 10-20% of patients with advanced Prostate cancer will progress to Castration Resistant Prostate Cancer (CRPC) within five years during ADT, and over 80% of these patients will have metastatic disease at the time of CRPC diagnosis.

ERLEADA® (Apalutamide) is an orally administered Androgen Receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. ERLEADA® inhibits AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription. ERLEADA® is presently approved for the treatment of patients with metastatic Castration Sensitive Prostate Cancer (CSPC) and non-metastatic Castration Resistant Prostate Cancer (CRPC).

TITAN (Targeted Investigational Treatment Analysis of Novel Anti-androgen) is an international, randomized, placebo-controlled, double-blind, Phase III trial, conducted to determine whether treatment with ERLEADA® would result in longer radiographic Progression Free Survival (PFS) and Overall Survival (OS) than placebo, with an acceptable Safety profile and Health-Related Quality of Life, among patients with metastatic CSPC, who were receiving concomitant ADT. In this study a 1052 patients were randomly assigned 1:1 to receive ERLEADA® plus ADT (N=525) or placebo plus ADT (N=527). Patients received ERLEADA® 240 mg orally once daily, in addition to continuous ADT. The median age was 68 years and eligible patients had adenocarcinoma of the prostate with distant metastatic disease and were castration sensitive (patients were not receiving ADT at the time of disease progression). Previous treatment for prostate cancer was limited to no more than 6 cycles of Docetaxel, with no evidence of progression during treatment. A total of 16% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 11% had received previous Docetaxel therapy and 63% had high-volume disease. The co-Primary end points were OS and radiographic PFS (rPFS).

At the first interim analysis, with a median follow up of 22.7 months, ERLEADA® significantly improved dual Primary end points of OS (HR for death=0.67; P=0.005) and rPFS (HR for radiologic progression or death=0.48; P<0.001; Chi et al. NEJM. 2019). When this data was reported, OS information was from the first planned interim analysis, whereas rPFS data was final. TITAN study was then unblinded, allowing patients without progression who were still receiving placebo, to cross over to ERLEADA®. The authors in this publication reported the final analysis of efficacy and safety results from TITAN study.

At a median follow up was 44.0 months, the previous efficacy data was confirmed even after 39.5% of patients in the placebo group crossed over to receive ERLEADA®. Median treatment durations were 39.3 months with ERLEADA® in the ERLEADA® group, 20.2 months with placebo in the placebo group, and 15.4 months with ERLEADA® in placebo-treated patients who crossed over. In the intention-to-treat population, including patients who crossed over from the placebo group, the median Overall Survival was Not Reached in the ERLEADA® group versus 52.2 months in the placebo group (HR=0.65, P < 0.0001). The OS was superior in the ERLEADA® group compared with the placebo group despite crossover and the 4-year survival rates were 65% with ERLEADA® versus 52% with placebo. When the analysis was adjusted for crossover, the Hazard Ratio further improved to 0.52 (P<0.0001). At final analysis, cytotoxic chemotherapy had been initiated in 13.1% of ERLEADA®-treated patients versus 23.9% of placebo-treated patients (HR=0.47, P<0.0001). Secondary endpoints including second PFS (PFS2) was also in favor of ERLEADA®, and Health-Related Quality of Life (HRQoL) was maintained in the ERLEADA® group throughout the study and was not different from the placebo group. Safety was consistent with previous reports.

The authors concluded that with close to 4 years of follow up, the final analysis of the TITAN study demonstrated that among patients with metastatic Castrate Sensitive Prostate Cancer, ERLEADA® plus ADT provided an improvement in Overall Survival with a 35% reduction in risk of death, which further increased to 48% reduction, after adjusting for patients who had crossed over from placebo to ERLEADA®. Further, ERLEADA® also delayed castration resistance, and maintained Quality of Life.

Apalutamide in Patients with Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. Chi KN, Chowdhury S, Bjartell A, et al. J Clin Oncol. 2021 Apr 29;JCO2003488. doi: 10.1200/JCO.20.03488. Online ahead of print.

Prostate Cancer Risk Associated with Familial and Hereditary Cancer Syndromes

SUMMARY: Prostate Cancer is the most common cancer in American men with the exclusion of skin cancer, and 1 in 9 men will be diagnosed with Prostate Cancer during their lifetime. It is estimated that in the United States, about 191,930 new cases of Prostate Cancer will be diagnosed in 2020 and 33,330 men will die of the disease. The five year survival among patients first diagnosed with metastatic disease is approximately 30%. Early detection and treatment may improve outcomes. Risk factors for Prostate Cancer include age, ethnicity, and family history of Prostate Cancer. In individuals with a family history of Prostate Cancer in one or more first-degree relatives, the Relative Risk of Prostate Cancer increases approximately 2-3 fold, and the risk increases with an increasing number of affected relatives, and is inversely related to the age at time of diagnosis among those relatives.

It is estimated that approximately 40% of all diagnosed Prostate Cancers are inherited and Prostate Cancer risk also has been implicated in other familial cancer syndromes such as Hereditary Breast and Ovarian Cancer (HBOC) syndrome and Lynch Syndrome (LS). HBOC syndrome typically is found in families with early onset cancer and multiple cancer diagnoses such as, breast, ovarian and pancreatic cancer. Tumor suppressor DNA repair genes BRCA1 and BRCA2, has been implicated in Prostate Cancer, particularly in HBOC families. Patients with a BRCA1 mutation have a nearly 2-fold Relative Risk of Prostate Cancer among men less than 65 years, whereas those with BRCA2 mutations have a more than 7 fold Relative Risk. Further, patients with BRCA2 mutations are also associated with clinically aggressive disease, progression, and higher rates of cancer-specific mortality. It is estimated that the frequency of BRCA2 mutations ranges from 1-3%. The National Comprehensive Cancer Network (NCCN) recommends that BRCA2 mutation carriers begin Prostate Cancer screening with PSA testing and a digital rectal exam by age 40, and that BRCA1 mutation carriers consider testing at age 40, as well.

Lynch Syndrome, or Hereditary Non-Polyposis Colorectal Cancer, is associated with germline DNA mismatch repair defects, and individuals with Lynch Syndrome are 2-5 times more likely to develop Prostate Cancer during their lifetimes.

The purpose of this population-based study was to quantify the Relative Risk of Prostate Cancer associated with different family cancer histories such as Hereditary Prostate Cancer, Hereditary Breast and Ovarian Cancer syndrome and Lynch Syndrome. The Utah Population Database was chosen as it is very large and linked to the Utah Cancer Registry. The Relative Risk for Prostate Cancer in general, as well as the risks for three Prostate Cancer subgroups- early onset, lethal, and clinically significant Prostate Cancers, was evaluated.

The authors using the Utah Population Database identified 619,630 men, 40 years or older, who were members of a pedigree that included at least 3 consecutive generations. Each individual was then assessed for family history of Hereditary Prostate Cancer, Hereditary Breast and Ovarian Cancer (HBOC) or Lynch syndrome, as well as his own Prostate Cancer status. The participant’s own cancer disease status was not used in any of the family history definitions. Family history of Hereditary Prostate Cancer was defined as 3 or more first-degree relatives with Prostate Cancer, or Prostate Cancer in 3 or more affected relatives diagnosed in 3 successive generations of the same lineage (paternal or maternal), or 2 or more first-degree relatives both diagnosed with early-onset disease (55 years or less). The NCCN Guidelines for BRCA-related Breast and/or Ovarian Cancer Syndrome were adapted for a family history of HBOC and revised Bethesda Guidelines were adapted for Lynch Syndrome, to determine if an individual had a positive family history of Lynch Syndrome. All Prostate Cancer occurences were classified into one or more subtypes: Early-onset Prostate Cancer defined as Prostate Cancer diagnosed at age 55 years or less, Lethal Prostate Cancer was identified if Prostate Cancer was listed as the primary cause of death on a death certificate, and Clinically significant Prostate Cancer if the Gleason score was 7 or more, direct extension, regional lymph node involvement or presence of distant metastases.

The overall prevalence of Prostate Cancer for the cohort was 5.9% (N=36,360), of whom 7% had Early onset disease, 11.1% had Lethal disease and 41.8% had Clinically significant disease. The median age at time of diagnosis was 69 years, approximately 70% of men were diagnosed with organ-confined disease, and approximately 6% were first diagnosed with metastatic disease.

Family history of Hereditary Prostate Cancer was associated with the highest risk for all Prostate Cancer subtypes combined, with a 2.3-fold increase in risk for Prostate Cancer overall (Relative Risk 2.30). This was followed by Hereditary Breast and Ovarian Cancer, with a Relative Risk of 1.47, and Lynch syndrome with a Relative Risk of 1.16.

Hereditary Prostate Cancer was associated with a near 4-fold increase in risk for early onset Prostate Cancer (RR=3.93). Hereditary Prostate Cancer also was associated with higher risks for both Lethal Prostate Cancer (RR=2.21) and Clinically significant disease (RR=2.32). Overall, modest elevations in risk were associated with Lynch Syndrome, with a 34% increase in risk for early onset disease (RR=1.34) and a small increase in the risk for Clinically significant disease (RR=1.15).

It was concluded from this investigation of a large, population-based family database that, targeting high-risk populations such as those with Hereditary Prostate Cancer early, with genetic screening and cancer surveillance, is indicated. This study also demonstrated the importance of well-ascertained family history information, for determining Prostate Cancer risk, as well as determining important Prostate Cancer subsets such as Early onset and Lethal disease. The authors added that this is the first study that compared the risk of Prostate Cancer in men with Hereditary Prostate Cancer, with families having HBOC or Lynch syndrome in the same population.

Risk of Prostate Cancer Associated With Familial and Hereditary Cancer Syndromes. Beebe-Dimmer JL, Kapron AL, Fraser AM, et al. J Clin Oncol. 2020;38:1807-1813

2021 ASCO GU Cancers Symposium: Apalutamide and Abiraterone plus Prednisone Improves PFS in Chemo-Naive mCRPC Patients

SUMMARY: Prostate cancer is the most common cancer in American men with the exclusion of skin cancer, and 1 in 8 men will be diagnosed with prostate cancer during their lifetime. It is estimated that in the United States, about 248,530 new cases of prostate cancer will be diagnosed in 2021 and 34,130 men will die of the disease. The development and progression of prostate cancer is driven by androgens. Androgen Deprivation Therapy (ADT) or testosterone suppression has therefore been the cornerstone of treatment of advanced prostate cancer, and is the first treatment intervention. Androgen Deprivation Therapies have included bilateral orchiectomy or Gonadotropin Releasing Hormone (GnRH) analogues, with or without first generation Androgen Receptor (AR) inhibitors such as CASODEX® (Bicalutamide), NILANDRON® (Nilutamide) and EULEXIN® (Flutamide) or with second generation anti-androgen agents, which include ZYTIGA® (Abiraterone), XTANDI® (Enzalutamide), ERLEADA® (Apalutamide) and NUBEQA® (Darolutamide). Approximately 10-20% of patients with advanced Prostate cancer will progress to Castration Resistant Prostate Cancer (CRPC) within five years during ADT, and over 80% of these patients will have metastatic disease at the time of CRPC diagnosis. Among those patients without metastases at CRPC diagnosis, 33% are likely to develop metastases within two years. Progression to Castration Resistant Prostate Cancer (CRPC) often manifests itself with a rising PSA (Prostate Specific Antigen), and watchful waiting is often recommended in men with non-metastatic CRPC. However, those with a rapidly rising PSA on ADT (doubling time of less than 8-10 months), are at significantly greater risk of developing metastases and death. The estimated mean survival of patients with CRPC is 9-36 months, and there is therefore an unmet need for new effective therapies.MOA-of-Androgen-Receptor-Targeted-Agents

Expression of Androgen Receptor (AR) in prostate cancer is heterogeneous and this AR heterogeneity is accentuated in advanced metastatic and relapsed prostate cancer with varying degrees of AR resistance and sensitivity. Both single agent ERLEADA® (Apalutamide) and ZYTIGA® (Abiraterone acetate) in combination with Prednisone, are approved for the treatment of metastatic CRPC. They have distinct mechanisms of action on the Androgen Receptors. Apalutamide is an Androgen Receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. Apalutamide inhibits AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription. Abiraterone acetate is an androgen biosynthesis inhibitor that inhibits CYP17, an enzyme expressed in testicular, adrenal, and prostatic tumor tissues, and is required for androgen biosynthesis. The ACIS trial was conducted to study the benefit of androgen annihilation by combining these two drugs (dual inhibition), for the first-line treatment of metastatic CRPC.

ACIS is a randomized, double-blind, placebo-controlled, multicenter study Phase III trial in which the efficacy and safety of single agent Apalutamide and Abiraterone acetate along with Prednisone plus ADT, was compared to placebo and Abiraterone acetate with Prednisone plus ADT, in patients with chemotherapy-naïve mCRPC. This study enrolled 982 chemo naïve patients with metastatic CRPC, who had disease progression on ADT, and were on no other life-prolonging treatment since diagnosis. Patients were randomized 1:1 to receive Apalutamide 240 mg daily along with Abiraterone acetate 1000 mg daily plus Prednisone 5 mg twice daily, all given orally (N=492) versus Placebo along with Abiraterone Acetate plus Prednisone (N=490). All patients were also on Androgen Deprivation Therapy. The median patient age was 71 years, 53% of patients had a Gleason score of 7 or more at initial diagnosis, about 85% had bone metastases, 48% had lymph node metastases and 15% had visceral metastases. Baseline characteristics were comparable in both treatment groups.
The Primary end point was radiographic Progression Free Survival (rPFS), defined from randomization date to radiographic progression date or death. Secondary end points included PSA response, Overall Survival (OS), initiation of cytotoxic chemotherapy, and pain progression.

This trial met its Primary endpoint of rPFS benefit with androgen annihilation, and the Apalutamide plus Abiraterone combination prolonged rPFS from 16.6 months to 22.6 months (HR=0.69, P<0.0001), suggesting a 31% reduction in the risk of radiographic disease progression and death. However, after 54.8 months of median follow-up, Overall Survival was numerically higher but not statistically significantly higher with Apalutamide plus Abiraterone combination (36.2 months versus 33.7 months, P=0.498). In the pre-specified subgroup analysis, the Apalutamide plus Abiraterone combination was more favorable in patients 75 years and older and in those with visceral metastases. More patients receiving Apalutamide plus Abiraterone combination had a PSA decline greater than 50%. In an exploratory analysis of biomarkers of response, tumors classified as luminal by the PAM50 signature score, or those having high AR activity expression signatures, trended towards improved rPFS and OS with the Apalutamide plus Abiraterone combination. There were no new safety signals noted with the Apalutamide plus Abiraterone combination, and based on FACT (Functional Assessment of Cancer Therapy-Prostate) -P score, Quality of Life was comparable between treatment groups.

It was concluded that the ACIS trial met its Primary endpoint, and when compared to Abiraterone with ADT, a combination of Apalutamide plus Abiraterone along with ADT demonstrated a 31% reduction in risk of radiographic progression or death, in chemo-naive mCRPC patients.

Final results from ACIS, a randomized, placebo (PBO)-controlled double-blind phase 3 study of apalutamide (APA) and abiraterone acetate plus prednisone (AAP) versus AAP in patients (pts) with chemo-naive metastatic castration-resistant prostate cancer (mCRPC). Rathkopf DE, Efstathiou E, Attard G, et al. On behalf of the ACIS investigators. J Clin Oncol 39, 2021 (suppl 6; abstr 9)

FDA Approves ORGOVYX® for Advanced Prostate Cancer

SUMMARY: The FDA on December 18, 2020 approved the first oral Gonadotropin-Releasing Hormone (GnRH) receptor antagonist, ORGOVYX® (Relugolix), for adult patients with advanced prostate cancer. Prostate cancer is the most common cancer in American men with the exclusion of skin cancer, and 1 in 9 men will be diagnosed with prostate cancer during their lifetime. It is estimated that in the United States, about 191,930 new cases of prostate cancer will be diagnosed in 2020 and 33,330 men will die of the disease. The development and progression of prostate cancer is driven by androgens. Androgen Deprivation Therapy (ADT) or testosterone suppression has therefore been the cornerstone of treatment of advanced prostate cancer, and is the first treatment intervention. Androgen Deprivation Therapies have included bilateral orchiectomy or Gonadotropin Releasing Hormone (GnRH) analogues, with or without first generation Androgen Receptor (AR) inhibitors such as CASODEX® (Bicalutamide), NILANDRON® (Nilutamide) and EULEXIN® (Flutamide) or with second generation anti-androgen agents, which include ZYTIGA® (Abiraterone), XTANDI® (Enzalutamide), ERLEADA® (Apalutamide) and NUBEQA® (Darolutamide).

Androgen Deprivation Therapies such as GnRH analogs/Luteinizing Hormone Releasing Hormone (LHRH) agonists are standard treatment for patients with advanced prostate cancer. These agents when first administered trigger an initial surge in Luteinizing Hormone, Follicle Stimulating Hormone (FSH), and testosterone levels. With continuous administration, LHRH agonists desensitize the pituitary receptor and suppress the production of Luteinizing Hormone and testosterone, thus blocking the pulsatile secretion of GnRH by the hypothalamus. LHRH agonists however do not fully suppress FSH which is a potential mitogenic growth factor for prostate cancer cells. The initial testosterone surge may result in flaring up of symptoms such as bone pain, obstructive urinary symptoms, and rarely spinal cord compression. For this reason, anti-androgen agents are recommended for the first few weeks after initiation of an LHRH agonist. LHRH agonists have been shown to increase the near-term risk of major adverse cardiovascular events, by promoting plaque destabilization and rupture.

Degarelix (FIRMAGON®) is a GnRH antagonist, and the depot injection was approved by the FDA in December 2018. Degarelix suppresses both Luteinizing Hormone and FSH, resulting in rapid testosterone suppression, without an initial testosterone surge. This agent however has to be administered monthly and approximately 40% of patients experience reactions at the injection site.

ORGOVYX® is a highly selective, GnRH antagonist that can be given orally once daily, and has a half-life of 25 hours. In multiple Phase I and Phase II studies, ORGOVYX® has been shown to lower testosterone levels by rapidly inhibiting the pituitary release of Luteinizing Hormone and FSH. The HERO trial is a multinational, randomized, open-label, Phase III study, which evaluated the efficacy and safety of ORGOVYX®, an oral GnRH antagonist, as compared with those of Leuprolide (LUPRON®) (GnRH agonist), in men with advanced prostate cancer. In this study, a total of 930 patients were randomly assigned in a 2:1 ratio to receive either ORGOVYX® 120 mg orally once daily, after a single oral loading dose of 360 mg (N=622) or Leuprolide acetate 22.5 mg IM every 3 months (N=308), for 48 weeks.MOA-of-GnRH-Agonists-and-Antagonists

Eligible patients had one of three clinical disease presentations: 1) Evidence of biochemical (PSA) or clinical relapse after local primary intervention with curative intent. 2) Newly diagnosed hormone-sensitive metastatic disease. 3) Advanced localized disease unlikely to be cured by local primary intervention with curative intent. Patients with major adverse cardiovascular events within 6 months before trial initiation were excluded. Patients were stratified according to the presence or absence of metastatic disease, as well as age (75 yrs or less, and over 75 years). Approximately 32% of patients had metastatic disease and 50% had biochemical recurrence after definitive treatment. The Primary endpoint was sustained testosterone suppression to castrate levels (less than 50 ng/dL) through 48 weeks. Secondary end points included noninferiority of ORGOVYX® to Leuprolide with respect to sustained castration rate, castrate levels of testosterone on day 4, and profound castrate levels (less than 20 ng/dL) on day 15. Testosterone recovery after discontinuation of the trial drug was to be evaluated in a subgroup of patients. The median follow up time in both groups, including the 30-day safety follow-up period for adverse events, was 52 weeks.

ORGOVYX® was associated with a significantly higher rate of maintained castrate levels of testosterone, when compared to Leuprolide. Castrate levels of testosterone were maintained through 48 weeks in 96.7% of patients in the ORGOVYX® group compared to 88.8% of patients in the Leuprolide group. The difference of 7.9 percentage points showed noninferiority as well as superiority of ORGOVYX® (P<0.001 for superiority) over Leuprolide. All other key Secondary end points showed superiority of ORGOVYX® over Leuprolide (P<0.001). These endpoints included the percentage of patients with castrate levels of testosterone on day 4 (56% versus 0%) and on day 15 (98.7% versus 12%), testosterone suppression to less than 20ng/dL on day 15 (78.4% versus 1%) and confirmed PSA response of more than 50% decrease at day 15 (79.4% versus 19.8%; P<0.001). In the subgroup of 184 patients followed for testosterone recovery, the mean testosterone level 90 days after treatment discontinuation was 288.4 ng/dL in the ORGOVYX® group and 58.6 ng/dL in the Leuprolide group. The incidence of major adverse cardiovascular events among all the patients was 2.9% in the ORGOVYX® group and 6.2% in the Leuprolide group (HR=0.46).

The authors concluded that in this trial involving men with advanced prostate cancer, ORGOVYX® achieved rapid and sustained suppression of testosterone levels that was superior to that with Leuprolide, with a 54% lower risk of major adverse cardiovascular events.

Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. Shore ND, Saad F, Cookson MS, et al. for the HERO Study Investigators. N Engl J Med 2020; 382:2187-2196.

RUBRACA® in Metastatic Castrate Resistant Prostate Cancer with BRCA Mutations

SUMMARY: Prostate cancer is the most common cancer in American men with the exclusion of skin cancer, and 1 in 9 men will be diagnosed with Prostate cancer during their lifetime. It is estimated that in the United States, about 191,930 new cases of Prostate cancer will be diagnosed in 2020 and 33,330 men will die of the disease.

The development and progression of Prostate cancer is driven by androgens. Androgen Deprivation Therapy (ADT) or testosterone suppression has therefore been the cornerstone of treatment of advanced Prostate cancer and is the first treatment intervention. Androgen Deprivation Therapies have included bilateral orchiectomy or Gonadotropin Releasing Hormone (GnRH) analogues, with or without first generation Androgen Receptor (AR) inhibitors such as CASODEX® (Bicalutamide), NILANDRON® (Nilutamide) and EULEXIN® (Flutamide) or with second-generation, anti-androgen agents, which include, ZYTIGA® (Abiraterone), XTANDI® (Enzalutamide) and ERLEADA® (Apalutamide). Approximately 10-20% of patients with advanced Prostate cancer will progress to Castration Resistant Prostate Cancer (CRPC) within five years during ADT, and over 80% of these patients will have metastatic disease at the time of CRPC diagnosis. The estimated mean survival of patients with CRPC is 9-36 months, and there is therefore an unmet need for new effective therapies.

DNA damage is a common occurrence in daily life by UV light, ionizing radiation, replication errors, chemical agents, etc. This can result in single and double strand breaks in the DNA structure which must be repaired for cell survival. The two vital pathways for DNA repair in a normal cell are BRCA1/BRCA2 and PARP. BRCA1 and BRCA2 genes recognize and repair double strand DNA breaks via Homologous Recombination Repair (HRR) pathway. Homologous Recombination is a type of genetic recombination, and is a DNA repair pathway utilized by cells to accurately repair DNA double-stranded breaks during the S and G2 phases of the cell cycle, and thereby maintain genomic integrity. Homologous Recombination Deficiency (HRD) is noted following mutation of genes involved in HR repair pathway. At least 15 genes are involved in the Homologous Recombination Repair (HRR) pathway including BRCA1, BRCA2 and ATM genes. The BRCA1 gene is located on the long (q) arm of chromosome 17 whereas BRCA2 is located on the long arm of chromosome 13. BRCA1 and BRCA2 are tumor suppressor genes and functional BRCA proteins repair damaged DNA, and play an important role in maintaining cellular genetic integrity. They regulate cell growth and prevent abnormal cell division and development of malignancy.

Recently published data has shown that deleterious Germline and/or Somatic mutations in BRCA1, BRCA2, ATM, or other Homologous Recombination DNA-repair genes, are present in about 25% of patients with advanced prostate cancer, including mCRPC. Approximately 12% of men with mCRPC harbor a deleterious BRCA1 or BRCA2 mutation (BRCA1, 2%; BRCA2, 10%). Mutations in BRCA1 and BRCA2 also account for about 20-25% of hereditary breast cancers, about 5-10% of all breast cancers, and 15% of ovarian cancers. BRCA mutations can either be inherited (Germline) and present in all individual cells or can be acquired and occur exclusively in the tumor cells (Somatic). Somatic mutations account for a significant portion of overall BRCA1 and BRCA2 aberrations. Loss of BRCA function due to frequent somatic aberrations likely deregulates HR pathway, and other pathways then come in to play, which are less precise and error prone, resulting in the accumulation of additional mutations and chromosomal instability in the cell, with subsequent malignant transformation. HRD therefore indicates an important loss of DNA repair function. The PARP (Poly ADP Ribose Polymerase), family of enzymes include, PARP1and PARP2, and is a related enzymatic pathway that repairs single strand breaks in DNA. In a BRCA mutant, the cancer cell relies solely on PARP pathway for DNA repair to survive. PARP inhibitors trap PARP onto DNA at sites of single-strand breaks, preventing their repair and generating double-strand breaks that cannot be repaired accurately in tumors harboring defects in Homologous Recombination Repair pathway genes, such as BRCA1 or BRCA2 mutations, and this leads to cumulative DNA damage and tumor cell death.MOA-of-RUBRACA

RUBRACA® (Rucaparib) is an oral, small molecule inhibitor of PARP. TRITON2 is an international, multicenter, open-label, single arm, Phase II trial, in which patients with BRCA-mutated mCRPC, who had progressed after one to two lines of next-generation Androgen Receptor-directed therapy and one taxane-based chemotherapy for mCRPC were included. In this study, 115 mCRPC patients with either Germline or Somatic BRCA mutations, with or without measurable disease were enrolled, of whom 62 patients (54%) had measurable disease at baseline. Patients received RUBRACA® 600 mg orally twice daily and concomitant GnRH analog or had prior bilateral orchiectomy. Treatment was continued until disease progression or unacceptable toxicity. The median patient age was 72 years, majority of patients had an ECOG performance status of 0 or 1, 67% of patients had Gleason score of 8 or more at diagnosis, 68% had bone-only disease and 47% had 10 or more bone lesions. The Primary endpoint was Objective Response Rate (ORR) by blinded IRR (Independent Radiology Review), as well as ORR by investigator assessment. Secondary end points included Duration of Response (DOR) in those with measurable disease, locally assessed PSA response rate (50% or more decrease from baseline) rate, Overall Survival (OS), and Safety. The median follow up was 17.1 months.

The confirmed ORR for the IRR-evaluable population was 43.5%, and the confirmed ORR for the investigator-evaluable population was 50.8%. The median DOR was not evaluable and 56% of patients with confirmed Objective Responses had a DOR of 6 months or more. The confirmed PSA response rate was 54.8% and the median time to PSA response was 1.9 months. The Objective Response Rates were similar for patients with a Germline or Somatic BRCA mutations, and for patients with a BRCA1 or BRCA2 mutations. However, a higher PSA response rate was observed in patients with a BRCA2 mutation. The median radiographic Progression Free Survival was 9.0 months per IRR assessment and 8.5 months per investigator assessment. The OS data were not yet mature at the time of the analysis. The most frequent Grade 3 or more treatment related Adverse Event was anemia (25.2%).

It was concluded that RUBRACA® demonstrates promising efficacy in patients with mCRPC with deleterious BRCA mutations. TRITON3 study is evaluating RUBRACA® versus physician’s choice of second-line AR-directed therapy or Docetaxel, in chemotherapy-naïve patients with mCRPC and alterations in BRCA1/2, who progressed on one prior AR-directed therapy.

Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration. Abida W, Patnaik A, Campbell D, et al. on behalf of the TRITON2 investigators. J Clin Oncol. 2020;38:3763-3772.

Risk of Prostate Cancer Associated With Familial and Hereditary Cancer Syndromes

SUMMARY: Prostate Cancer is the most common cancer in American men with the exclusion of skin cancer, and 1 in 9 men will be diagnosed with Prostate Cancer during their lifetime. It is estimated that in the United States, about 191,930 new cases of Prostate Cancer will be diagnosed in 2020 and 33,330 men will die of the disease. The five year survival among patients first diagnosed with metastatic disease is approximately 30%. Early detection and treatment may improve outcomes. Risk factors for Prostate Cancer include age, ethnicity, and family history of Prostate Cancer. In individuals with a family history of Prostate Cancer in one or more first-degree relatives, the Relative Risk of Prostate Cancer increases approximately 2-3 fold, and the risk increases with an increasing number of affected relatives, and is inversely related to the age at time of diagnosis among those relatives.

It is estimated that approximately 40% of all diagnosed Prostate Cancers are inherited and Prostate Cancer risk also has been implicated in other familial cancer syndromes such as Hereditary Breast and Ovarian Cancer (HBOC) syndrome and Lynch Syndrome (LS). HBOC syndrome typically is found in families with early onset cancer and multiple cancer diagnoses such as, breast, ovarian and pancreatic cancer. Tumor suppressor DNA repair genes BRCA1 and BRCA2, has been implicated in Prostate Cancer, particularly in HBOC families. Patients with a BRCA1 mutation have a nearly 2-fold Relative Risk of Prostate Cancer among men less than 65 years, whereas those with BRCA2 mutations have a more than 7 fold Relative Risk. Further, patients with BRCA2 mutations are also associated with clinically aggressive disease, progression, and higher rates of cancer-specific mortality. It is estimated that the frequency of BRCA2 mutations ranges from 1-3%. The National Comprehensive Cancer Network (NCCN) recommends that BRCA2 mutation carriers begin Prostate Cancer screening with PSA testing and a digital rectal exam by age 40, and that BRCA1 mutation carriers consider testing at age 40, as well.

Lynch Syndrome, or Hereditary Non-Polyposis Colorectal Cancer, is associated with germline DNA mismatch repair defects, and individuals with Lynch Syndrome are 2-5 times more likely to develop Prostate Cancer during their lifetimes.

The purpose of this population-based study was to quantify the Relative Risk of Prostate Cancer associated with different family cancer histories such as Hereditary Prostate Cancer, Hereditary Breast and Ovarian Cancer syndrome and Lynch Syndrome. The Utah Population Database was chosen as it is very large and linked to the Utah Cancer Registry. The Relative Risk for Prostate Cancer in general, as well as the risks for three Prostate Cancer subgroups- early onset, lethal, and clinically significant Prostate Cancers, was evaluated.

The authors using the Utah Population Database identified 619,630 men, 40 years or older, who were members of a pedigree that included at least 3 consecutive generations. Each individual was then assessed for family history of Hereditary Prostate Cancer, Hereditary Breast and Ovarian Cancer (HBOC) or Lynch syndrome, as well as his own Prostate Cancer status. The participant’s own cancer disease status was not used in any of the family history definitions. Family history of Hereditary Prostate Cancer was defined as 3 or more first-degree relatives with Prostate Cancer, or Prostate Cancer in 3 or more affected relatives diagnosed in 3 successive generations of the same lineage (paternal or maternal), or 2 or more first-degree relatives both diagnosed with early-onset disease (55 years or less). The NCCN Guidelines for BRCA-related Breast and/or Ovarian Cancer Syndrome were adapted for a family history of HBOC and revised Bethesda Guidelines were adapted for Lynch Syndrome, to determine if an individual had a positive family history of Lynch Syndrome. All Prostate Cancer occurences were classified into one or more subtypes: Early-onset Prostate Cancer defined as Prostate Cancer diagnosed at age 55 years or less, Lethal Prostate Cancer was identified if Prostate Cancer was listed as the primary cause of death on a death certificate, and Clinically significant Prostate Cancer if the Gleason score was 7 or more, direct extension, regional lymph node involvement or presence of distant metastases.

The overall prevalence of Prostate Cancer for the cohort was 5.9% (N=36,360), of whom 7% had Early onset disease, 11.1% had Lethal disease and 41.8% had Clinically significant disease. The median age at time of diagnosis was 69 years, approximately 70% of men were diagnosed with organ-confined disease, and approximately 6% were first diagnosed with metastatic disease.

Family history of Hereditary Prostate Cancer was associated with the highest risk for all Prostate Cancer subtypes combined, with a 2.3-fold increase in risk for Prostate Cancer overall (Relative Risk 2.30). This was followed by Hereditary Breast and Ovarian Cancer, with a Relative Risk of 1.47, and Lynch syndrome with a Relative Risk of 1.16.

Hereditary Prostate Cancer was associated with a near 4-fold increase in risk for early onset Prostate Cancer (RR=3.93). Hereditary Prostate Cancer also was associated with higher risks for both Lethal Prostate Cancer (RR=2.21) and Clinically significant disease (RR=2.32). Overall, modest elevations in risk were associated with Lynch Syndrome, with a 34% increase in risk for early onset disease (RR=1.34) and a small increase in the risk for Clinically significant disease (RR=1.15).

It was concluded from this investigation of a large, population-based family database that, targeting high-risk populations such as those with Hereditary Prostate Cancer early, with genetic screening and cancer surveillance, is indicated. This study also demonstrated the importance of well-ascertained family history information, for determining Prostate Cancer risk, as well as determining important Prostate Cancer subsets such as Early onset and Lethal disease. The authors added that this is the first study that compared the risk of Prostate Cancer in men with Hereditary Prostate Cancer, with families having HBOC or Lynch syndrome in the same population.

Risk of Prostate Cancer Associated With Familial and Hereditary Cancer Syndromes. Beebe-Dimmer JL, Kapron AL, Fraser AM, et al. J Clin Oncol. 2020;38:1807-1813

XTANDI® Improves Overall Survival in Nonmetastatic Castration-Resistant Prostate Cancer

SUMMARY: Prostate cancer is the most common cancer in American men with the exclusion of skin cancer, and 1 in 9 men will be diagnosed with prostate cancer during their lifetime. It is estimated that in the United States, about 191,930 new cases of prostate cancer will be diagnosed in 2020 and 33,330 men will die of the disease.

The development and progression of prostate cancer is driven by androgens. Androgen Deprivation Therapy (ADT) or testosterone suppression has therefore been the cornerstone of treatment of advanced prostate cancer, and is the first treatment intervention. Androgen Deprivation Therapies have included bilateral orchiectomy or Gonadotropin Releasing Hormone (GnRH) analogues, with or without first generation Androgen Receptor (AR) inhibitors such as CASODEX® (Bicalutamide), NILANDRON® (Nilutamide) and EULEXIN® (Flutamide) or with second-generation, anti-androgen agents, which include ZYTIGA® (Abiraterone), XTANDI® (Enzalutamide), ERLEADA® (Apalutamide) and NUBEQA® (Darolutamide).

Approximately 10-20% of patients with advanced prostate cancer will progress to Castration Resistant Prostate Cancer (CRPC) within five years during ADT, and over 80% of these patients will have metastatic disease at the time of CRPC diagnosis (mCRPC). Among those patients without metastases at CRPC diagnosis, 33% are likely to develop metastases within two years. The estimated mean survival of patients with CRPC is 9-36 months. Progression to Castration Resistant Prostate Cancer (CRPC) often manifests itself with a rising PSA (Prostate Specific Antigen), and watchful waiting is often recommended in men with non-metastatic CRPC. However, those with a rapidly rising PSA on ADT (doubling time of less than 8-10 months), are at significantly greater risk of developing metastases and death.XTANDI-Mechanism-of-Action

XTANDI® (Enzalutamide) is an orally administered, second-generation, anti-androgen, with no reported agonistic effects. It competitively inhibits androgens and AR binding to androgens as well as AR nuclear translocation and interaction with DNA. It thus inhibits several steps in the AR signaling pathway and was designed to overcome acquired resistance to first-generation nonsteroidal anti-androgens. Previously published studies have shown that XTANDI® improved Overall Survival in metastatic CRPC, regardless of whether it was used before or after Docetaxel chemotherapy.

PROSPER trial is a multinational, double-blind, randomized, placebo-controlled Phase III study, conducted to assess the safety and efficacy of XTANDI® in patients with nonmetastatic CRPC. In this study, 1401 eligible patients were enrolled and randomized in a 2:1 ratio to receive XTANDI® 160 mg orally once daily (N=933) or placebo (N=468). Enrolled patients had rising PSA, with a PSA doubling time of 10 months or less, despite castrate levels of testosterone (0.50 ng/mL), while continuing to receive Androgen Deprivation Therapy (ADT) with either a gonadotropin-releasing hormone agonist or antagonist or with previous bilateral orchiectomy. A diagnosis of nonmetastatic CRPC was established based on conventional imaging such as CT scans, MRI and Bone scans. The median patient age was 73 years, and both treatment groups were well balanced. The Primary endpoint was Metastasis-Free Survival (MFS), defined as time from randomization to imaging-based progression, or time to death from any cause without evidence of imaging-based progression. Secondary endpoints included Overall Survival, time to PSA progression, PSA response rate and time to first use of a subsequent antineoplastic therapy, as well as health-related quality of life and frequency and severity of adverse events. At the primary analysis, the study met the Primary endpoint of MFS and treatment with XTANDI® significantly improved Metastasis-Free Survival. The authors in this publication reported results from the prespecified final analysis of Overall Survival.

The median Overall Survival was 67.0 months in the XTANDI® group and 56.3 months in the placebo group. XTANDI® plus Androgen Deprivation Therapy (ADT) lowered the risk of death by 27%, compared with placebo plus ADT (HR=0.73; P=0.001). This benefit was consistent across prespecified subgroups. XTANDI® was also associated with a delay in the use of a new subsequent antineoplastic therapy, and the median time to first use of new antineoplastic therapy was 66.7 months in the XTANDI® group and 19.1 months in the placebo group (HR=0.29). The most frequently reported Adverse Events with XTANDI® were fatigue and musculoskeletal events.

It was concluded that XTANDI® given along with Androgen Deprivation Therapy resulted in longer median Overall Survival, when compared with placebo plus ADT, among men with nonmetastatic, CRPC and a rapidly rising PSA level, with 27% lower risk of death. The authors however added that the classification of patients as having nonmetastatic disease may be impacted, with the availability of more sensitive imaging techniques, for earlier detection of metastasis.

Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. Sternberg CN, Fizazi K, Saad F, et al. for the PROSPER Investigators. N Engl J Med 2020; 382:2197-2206

PSMA-Targeted Imaging for Biochemically Recurrent Prostate Cancer

SUMMARY: Prostate cancer is the most common cancer in American men with the exclusion of skin cancer, and 1 in 9 men will be diagnosed with prostate cancer during their lifetime. It is estimated that in the United States, about 191,930 new cases of prostate cancer will be diagnosed in 2020 and 33,330 men will die of the disease.

The major source of PSA (Prostate Specific Antigen) is the prostate gland and the PSA levels are therefore undetectable within 6 weeks after Radical Prostatectomy. Similarly, following Radiation Therapy, there is a gradual decline in PSA before reaching a post treatment nadir. A detectable PSA level after Radical Prostatectomy, or a rising PSA level following Radiation Therapy, is considered PSA failure or biochemical recurrence. Approximately 35% of the patients with prostate cancer will experience PSA only relapse within 10 years of their primary treatment and a third of these patients will develop documented metastatic disease within 8 years following PSA only relapse.Defining-Biochemical-Recurrence

Rising PSA is therefore a sign of recurrent disease and identifying the site of recurrence can be of immense value for the clinician and can help determine the best course of therapy. The diagnostic accuracy of standard imaging tests, for the identification of sites of recurrence in patients with biochemical recurrence, is low. Almost 90% of the standard imaging tests such as CT/MRI and Bone Scan may be negative. More accurate non-invasive imaging techniques for the detection of recurrent tumor is therefore an unmet need. Prostascint, a Single Photon Emission Computerized Tomography (SPECT) radiopharmaceutical agent, was approved in 1999 for the diagnostic imaging of post-prostatectomy patients with a rising PSA. PET (Positron Emission Tomography) scans have largely superseded this study. FluDeoxyGlucose F18 (FDG), a glucose analogue is the most widely used PET radiotracer, but is not generally used as an imaging agent in prostate cancer. This is because good and reliable quality images are not feasible due to indolent growth of prostate cancers and the high urinary excretion of FDG. The other PET radiotracer that is available, Choline C11, has been shown to improve cancer detection in men with biochemical recurrent prostate cancer, but this agent has a short half life of 20 minutes, requires greater patient preparation including 6 hours of fasting prior to administration of Choline C11, delivers higher radiation dose to patients and image quality is poor. The FDA in 2016 approved AXUMIN® (Fluciclovine F18), a novel molecular radiopharmaceutical diagnostic agent, for PET imaging in men with suspected prostate cancer recurrence, based on elevated PSA levels, following prior treatment. This study however is less likely to be positive with PSA less than 1 ng/mL, unless the doubling time is rapid. There is also higher false positive rate within the intact or treated prostate gland, and uptake may be absent in densely sclerotic lesions. Current imaging modalities are therefore inadequate for localizing and characterizing occult disease in men with biochemically recurrent prostate cancer.

F-18 DCFPyL is a novel PET imaging agent that binds selectively with high affinity to Prostate-Specific Membrane Antigen (PSMA), which is overexpressed in prostate cancer cells. CONDOR is a prospective, multicenter, randomized, Phase III trial, conducted to evaluate the diagnostic performance of PET/CT imaging with F-18 DCFPyL, a radiopharmaceutical targeting the extracellular domain of PSMA. This study enrolled 208 men at 14 sites in the US and Canada, with a rising PSA level after definitive therapy and negative or equivocal standard-of-care imaging (eg, CT, MRI, bone scintigraphy). PET/CT imaging was performed 1-2 hours following administration of a single dose of F-18 DCFPyL. The median age was 68 yrs and the median time from diagnosis was 71 months. Approximately 50% of all patients had undergone Radical Prostatectomy, 35% underwent Radical Prostatectomy and Radiation Therapy, 15% had only received RadioTherapy, and 28% received at least one systemic therapy for their prostate cancer. Approximately 74% of patients had a total Gleason score below 8. All enrolled patients had biochemically recurrent metastatic Castration-Resistant Prostate Cancer, and a PSA of at least 0.2 ng/mL following radical prostatectomy, or at least 2 ng/mL over the nadir following prior Radiation Therapy, Cryotherapy or systemic therapy. The median PSA was 0.8 ng/mL, (PSA level at which most decisions about subsequent salvage focal or systemic therapies are made) and 31% of patients had a PSA of at least 2.0 ng/mL. All enrolled patients had no previous radiologic findings. The Primary endpoint was Correct Localization Rate of occult disease, as determined by three independent reviewers, and the Secondary endpoint was the impact of F-18 DCFPyL PET/CT imaging results on management of enrolled patients in this study.

The study met its Primary endpoint and the Correct Localization Rate of occult disease or the Positive Predictive Value ranged from 84.8% to 87% for the three independent reviewers. The Correct Localization Rate of occult disease was maintained regardless of PSA values and the F-18 DCFPyL PET/CT imaging detected disease even at the lowest of PSA values. Regarding the Secondary endpoint of impact of F-18 DCFPyL PET/CT imaging on treatment, 64% of patients had a change in management due to findings noted on the imaging study, of which 78% were attributable to positive findings on the imaging study, and 21.4% to negative findings on F-18 DCFPyL PET/CT imaging study. Specific changes in the treatment management included change in the goal of patients disease management from a noncurative approach to a curative salvage local therapy in 21% of patients, 28% changed from receiving salvage local therapy to systemic therapy or added systemic therapy, 23.9% changed from observation status to initiation of therapy and 4.4% changed from planned treatment to observation alone.

It was concluded that PSMA-targeted F-18 DCFPyL PET/CT imaging detected and localized occult disease in most men with biochemical recurrence, presenting with negative or equivocal findings on conventional imaging. Further, F-18 DCFPyL PET/CT imaging provided actionable information that led to change in treatment plans for the majority of patients, thus providing evidence that PSMA PET imaging may be valuable in men with recurrent or suspected metastatic prostate cancer.

Impact of PSMA-targeted imaging with 18F-DCFPyL-PET/CT on clinical management of patients (pts) with biochemically recurrent (BCR) prostate cancer (PCa): Results from a phase III, prospective, multicenter study (CONDOR). Morris MJ, Carroll PR, Saperstein L, et al. DOI: 10.1200/JCO.2020.38.15_suppl.5501 Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 5501-5501.