Ahead of the 2021 ASCO Annual Meeting, Michael S. Cookson, MD, co-editor in chief of Urology Times, shared his thoughts on the most pivotal abstracts in genitourinary cancer. Cookson is a professor at the University of Oklahoma Health Sciences Center (OUHSC), where he is also chairman of the Department of Urology.
The open-label phase 3 VISION trial (NCT03511664) accrued patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who received at least 1 novel androgen axis drug (eg, enzalutamide [Xtandi] or abiraterone acetate [Zytiga]) and were previously treated with 1 to 2 taxane regimens. Patients were randomized to the targeted radioligand therapy 177Lu-PSMA-617 (LuPSMA) plus best standard of care (BSC) or BSC alone.
The coprimary end points of the trial were overall survival (OS) and progression-free survival (PFS). Although no data were made available, it was announced in a press release ahead of ASCO that LuPSMA plus BSC improved both OS and PFS versus BSC alone.
“I haven’t seen the specific results yet, but anticipate these data will add additional support to making 177Lu-PSMA-617 a new standard of care of in men with mCRPC,” said Cookson.
The parallel assignment, double-blind phase 3 KEYNOTE-564 trial (NCT03142334) included patients with renal cell carcinoma (RCC) with a clear cell component who had undergone nephrectomy and had intermediate-high risk, high risk, or M1 no evidence of disease (M1 NED). Patients were not eligible to enroll if they had prior radiotherapy for RCC, or brain or bone metastatic lesions.
An independent data panel determined during an interim analysis that, as compared with placebo, single-agent pembrolizumab (Keytruda) achieved the trial’s primary end point by inducing a statistically significant and clinically meaningfully disease-free survival improvement. The trial remains ongoing to evaluate the key secondary end point of OS.
No new safety signals emerged as compared with previously reported trials of pembrolizumab.
Pembrolizumab is currently approved by the FDA for use in combination with axitinib (Inlyta) as a frontline treatment for patients with advanced RCC.
“I need to see to the results—efficacy benefit, number needed to treat, and adverse events (AEs)—but this could add an additional treatment option for high-risk kidney cancer post-nephrectomy,” said Cookson.
The authors explain in their abstract that in patients with localized MIBC, trimodal bladder preservation therapy (TMT), is a standard treatment option. TMT consists of various combinations of surgery, radiation, and chemotherapy. In this multicenter phase 2 trial, the authors examined the safety and efficacy of adding the immune checkpoint inhibitor pembrolizumab to standard TMT in this patient population. Specific TMT components used in this trial included transurethral resection of bladder tumor, hypofractionated radiotherapy, and gemcitabine chemotherapy.
The trial enrolled patients with stage cT2 to T4aN0M0 MIBC who were ineligible for or declined radical cystectomy. Other inclusion criteria were an ECOG performance score of 0 or 1 and no contraindications to either pembrolizumab or pelvic radiotherapy. The primary endpoint of the trial was bladder-intact disease-free survival at 2 years.
Based on an early data analysis, the researchers concluded that pembrolizumab plus TMT was well tolerated and demonstrated promising efficacy.
“This phase 2 study demonstrated reasonable data on safety and tolerability of a novel and contemporized approach to trimodal bladder sparing in patients with MIBC,” said Cookson.
Between November 2013 and December 2018, the study enrolled 1173 patients with de novo mCSPC. Standard of care (SOC) consisted of androgen-deprivation therapy (ADT) plus docetaxel in 710 patients and ADT alone in 463 patients. The median age was 67 years (IQR, 60-72), 57% had high-volume disease, and 43% had low volume disease.
Patients were randomized to SOC; SOC plus abiraterone acetate and prednisone; SOC plus radiotherapy to the primary tumor (RXT); or SOC plus abiraterone/prednisone plus RXT. The median follow-up was 3.5 years.
According to the abstract, “No interaction was detected between the effect of abiraterone and that of RXT, allowing [us] to pool abiraterone arms for comparisons.” Radiographic PFS (rPFS) was significantly approvedwith abiraterone in both the overall and ADT plus docetaxel populations. In the overall population, the rPFS was 4.5 years with the addition of abiraterone versus 2.2 years with SOC alone (HR, 0.54; P <.0001). The rPFS was 4.5 versus 2 years, respectively (HR, 0.50; P <.0001), in the ADT plus docetaxel group.
“The results demonstrate that adding abiraterone to ADT plus docetaxel significantly improves rPFS in men with de novo metastatic prostate cancer, with about 2.5 years of absolute benefit and no meaningful additional short-term toxicity. This could allow for a new combination approach to de novo mCSPC,” said Cookson.
The phase 3 EORTC-1333-GUCG trial (NCT02194842) compared the alpha particle–emitting radioactive therapeutic agent radium-223 (Xofigo) plus enzalutamide in patients with asymptomatic or mildly symptomatic mCRPC. Further, after the trial had been launched without this requirement, it was subsequently made mandatory to use bone protecting agents (BPA) after it was reported that there was a significant increase in the rate of fractures in the ERA223 trial (NCT02043678) among patients treated with radium-223 plus abiraterone.
Overall 253 patients were randomized, including 134 after BPA was made mandatory. BPA was received by 69.5% and 73.1% of the radium-223/enzalutamide and enzalutamide alone arms, respectively. The investigators reported that there were 39 patients overall who reported a fracture. Of these patients, 30 (20 in the combination arm) had not received BPA and 9 (4 in the combination arm) had received BPA.
“This is important to demonstrate that adding BPA to reduce skeletal-related events allows for continuation of novel second-generation antiandrogens in combination with radium-223,” said Cookson.
The study evaluated the genomic landscape in a cohort of 11,741 men with prostate cancer who received comprehensive genomic profiling (CGP) as part of routine clinical care. The cohort included 1422 men of African ancestry and 9242 men of European ancestry.
“Access to genomic information and precision medicine among minorities and in particular, African American men, is an important unmet need. The conclusions of this study speak for themselves: ‘This study encompasses the largest cohort, particularly of men of African ancestry in a genomic study, that defines CGP utilization, the genomic landscape, and therapeutic implications of CGP in prostate cancer across ancestry. Overall, there were largely similar rates of actionable gene alterations across ancestry. Notably, men of African ancestry were less likely to receive CGP earlier in their treatment course, and less likely to be treated on clinical trials, which could impact the genomic landscape, outcomes, and ultimately disparities,’” said Cookson.
In men at risk of prostate cancer, a standard recommendation is multiparametric MRI (mpMRI) of the prostate followed by targeted biopsy; however, use of this pathway may be inhibited by cost, inconsistent scan and reporting quality, and contraindication in patients with metallic implants or who have claustrophobia. An alternative to mpMRI that has emerged is multiparametric ultrasound (mpUSS). According to the abstract, mpUSS is a “point-of-care test with low cost that combines b-mode, color Doppler, elastography, and contrast enhancement.
The CADMUS trial compared the diagnostic performance of mpUSS and mpMRI in 306 patients. There was a 73.2% agreement in lesion detections between the 2 scans, and there was a 91.1% agreement on detection of clinically significant prostate cancer.
“The diagnostic performance of mpUSS approached that of mpMRI. The investigators also found that detection of significant cancer was enhanced by use of both mpUSS and mpMRI versus using one of the scans alone. This could set the stage for more widespread use of mpUSS,” said Cookson.
Beyond his roles at OUHSC, Cookson is also chief of urologic oncology at Stephenson Cancer Center in Oklahoma City, Oklahoma, and is president of the Society of Urologic Oncology and the South-Central Section of the American Urological Association.