Benjamin Saylor

In prostate cancer, the last decade of advancements have transformed the field. The abundance of new agents and technologies have revolutionized both prostate cancer screening and treatment.

During the 2022 LUGPA Annual Meeting Ashley Ross, MD, PhD, gave a presentation around the advanced and unmet needs in the field.

In an interview with Targeted Oncology™, Ross, professor of Urology at Northwestern University Feinberg School of Medicine in Chicago, Illinois, discussed his recent presentation as well as ongoing research prostate cancer genomics, PET for staging and for identification of local disease, and more.

 Could you describe some of the biggest unmet needs in prostate cancer, in your opinion?

 There have been a lot of advances in prostate cancer, particularly over the past decade or so. Most of the unmet needs, at least in the near term, are going to be about implementing new technologies. If you think about screening, we've had a lot of new tools that have come to bear for prostate cancer screening, in diagnosis of clinically significant disease, different biomarkers that can tell people their risk, use of imaging—MRI should be standard before biopsies—even the techniques we use for biopsy—perhaps transperineal approaches that reduce infection or the need for antibiotics. If we look at use of those across the country, they're not anywhere near 100%. Certainly, there are some health inequities as well that do stratify by socioeconomics, by race, and by location of the individual and the practitioner.

Even more so, if we look at advanced disease—the cancers that have been detected and we know are aggressive—there's been a lot of evidence that multimodal therapy for those men, even in the hormone-sensitive setting, that show that combining 2 or sometimes even 3 agents can increase their overall survival. But implementation of that has also been lagging. So, that's a life-saving therapy that hasn't been used. If we ask, "What is the path toward the next level of discoveries, pretending that we're implementing everything perfectly?", I think the frontier is going to be twofold. In the advanced setting, we have good tools that we can use upfront in the first and second line of therapy. But we still need to deal with transformed, more androgen-insensitive cancers, particularly ones that are moving towards the neuroendocrine or small-cell type. In the localized setting, it's all about reducing morbidity. There have been some advances there on the radiation side, there are some early signals that focal therapy may work. We're constantly improving surgical approaches as well.

Regarding the topic of emerging technologies and advances in prostate cancer treatment, could you specifically discuss the emergence of PSMA-PET imaging?

That's a great question. For a long time, in prostate cancer, we were imaging it based on things like size of lymph nodes or bone turnover, looking at technetium and MDP in MDP bone scans. PSMA-PET has been in development for a little over a decade, I believe. It's recently been approved in this country for staging, and staging across the board; really, anytime you suspect that there could be metastatic disease, whether that be upfront, or at time of recurrence, or at time of disease progression. It's been shown in randomized trials to be more accurate in all settings, and also more sensitive for detection of small amounts of disease. It's simply better. There's some early evidence that it may improve decision-making and outcomes for patients.

What we know for sure is it's just simply better imaging in terms of accuracy.

Right now, because of its superiority, PSMA-PET imaging should be the first thing that you move toward when you're trying to determine whether someone has metastatic disease. As I alluded to, there are still data that need to bear out to see whether use of PSMA-PET imaging to guide your treatment decisions is going to lead to better overall outcomes for patients or not. That still is yet to be determined. There are some controversies there, but at a basic level, understanding where the cancer is in a person's body and how much cancer is in the person's body is going to lead to better management.

What do you think have been some of the top advances in prostate cancer discovery over the past several years?

Over the past several years, I would say, as we mentioned, better imaging, particularly the utilization of PSMA tracers for PET imaging, has been a big advance. The second big advance in the localized disease setting and now somewhat in the more advanced disease setting is the use of genomics and genetics, specifically molecular tests like Decipher that give you better prognostic risk and having that guide you to treatment decisions. In the advanced setting, the biggest things have been understanding that combinatorial therapies upfront using androgen deprivation therapy, but also another androgen signaling inhibitor—perhaps even with chemotherapy in some cases—can improve overall survival. And then in the castrate-resistant setting, there is also the use of genetics to guide therapies like PARP inhibitors. Finally, there is the use of the PSMA as a radioligand to deliver therapeutics like lutetium PSMA. That's been mostly showing efficacy so far in later-stage disease in trials, but it's being trialed now in earlier-stage disease where I think the impact will be even greater; what I mean is earlier treatment lines.

Please discuss your own particular research.

I cover the spectrum of what we were just talking about. My research focuses a lot on using existing tools and implementation of those tools and then doing clinical trials. There was a point, maybe 5 to 10 years ago, where we were really very engrained in discovery of basic things. I had a wet lab where we were doing mouse experiments and genomics. Now, actually, we have a lot of tools available. My passion has been, how do we use them correctly? And then when we're utilizing them, how do we then disseminate that knowledge? Obviously, the standard of how we utilize these things correctly in humans are through trials, and so the more we can put people on trials and do clinical trials, the better it is. For example, we've done different PET imaging trials to look at PET for staging and for identification of local disease. We're using PET/MR in those studies. In terms of risk stratification, I've done a lot of work with genomics, looking at gene expression and how that can guide treatment decisions, how it can stratify cancers into different subtypes. Now, there's been a new understanding that maybe we can use artificial intelligence on pathology to recognize some of these characteristics in a higher throughput manner. We've done a lot on taking our screening tools together and putting them into different nomograms that can be easily used to identify risk of having prostate cancer and whether you need a biopsy. And then in the more advanced staging, partnering with industry, we're doing many trials at the hormone-sensitive status to see, can we extend overall survival, perhaps with even de-implementing some therapeutics, going to bimodal vs trimodal therapy?

Articles

In an interview with Targeted Oncology, Ashley Ross, MD, PhD, discussed his recent advanced in prostate cancer, research around prostate cancer genomics, PET for staging and for identification of local disease, and more. 

The Latest Treatment Advances in Prostate Cancer

The combination of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) led to a high overall response rate (ORR) and a manageable safety profile when used as treatment for patients with locally advanced or metastatic urothelial cancer.

The findings, derived from Cohort K of the EV-103 trial (NCT03288545), were presented at ESMO Congress 2022 by Jonathan E. Rosenberg, MD.

“Enfortumab and pembrolizumab as monotherapy have each shown anti-tumor activity with a survival benefit in pretreated patients with locally advanced or metastatic urothelial cancer. EV-pembro was previously evaluated in the EV-103 dose escalation/Cohort A, which showed encouraging safety and efficacy activity with a response rate of 73.3%,”

 said Rosenberg, chief of the Genitourinary Medical Oncology Service, Division of Solid Tumor Oncology, and Enno W. Ercklentz Chair at Memorial Sloan Kettering Cancer Center in New York, New York.

For the current study, “previously untreated cisplatin-ineligible patients with [locally advanced or metastatic urothelial cancer] were randomly assigned 1:1 to enfortumab vedotin (1.25.mg/kg) as monotherapy on Days 1 and 8 or in combination with P (200 mg) on Day 1 of 3-week cycles,” the authors wrote in their abstract. The primary end point was confirmed ORR by blinded independent central review. Duration of response (DOR) and safety were among the secondary end points.

In his presentation, Rosenberg stressed that the study was non comparative.

“We are not planning and we will not be performing any statistical comparisons formally between the arms. This study was really to understand the contribution of components of the different agents,” Rosenberg explained.

The patient population was predominantly male, and approximately 60% had impaired performance status. Visceral disease was presented more than 80% of patients, and approximately 40% were PD-L1 high; a proportion of patients were not evaluable because they did not have tumor to be submitted.

A total of 149 patients were included in the study, 76 of whom were treated with enfortumab vedotin plus pembrolizumab and 73 who were treated with enfortumab vedotin alone. The confirmed ORR (95% CI) for enfortumab vedotin plus pembrolizumab was 64.5%, and median DOR was not reached. Confirmed ORR for enfortumab vedotin alone was 45.2%, with a median DOR (95% CI) of 13.2 months.

Regarding adverse events (AEs), 15.6% of patients receiving enfortumab vedotin plus pembrolizumab stopped treatment due to an AE, and 24.3% of patients receiving enfortumab vedotin alone stopped treatment due to an AE. The most common AEs seen in patients receiving enfortumab vedotin plus pembrolizumab included fatigue, peripheral sensory neuropathy, alopecia, and maculo-papular rash. Eighteen (23.7%) serious treatment-related adverse events (TRAEs) were seen in the combination therapy group and 11 (15.1%) were seen in the monotherapy group. Three TRAEs leading to death (3.9%) were seen in the combination group and 2 (2.7%) were seen in the monotherapy group. Rosenberg reported that skin reactions were more frequent with patients receiving enfortumab vedotin plus pembrolizumab, although none were serious.

“Results from EV-103/KEYNOTE-869 Cohort K support the ongoing investigation of enfortumab vedotin and pembrolizumab in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who are in need of treatment options, and this combination may be an important therapeutic option for these patients,” Rosenberg said in a news release about the study.

1. Rosenberg JE, Milowsky M, Ramamurthy C, et al. Study EV-103 Cohort K: Antitumor activity of enfortumab vedotin (EV) monotherapy or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC).

2022;33(suppl 7):LBA73. doi:10.1016/annonc/annonc1089

2. Hoimes CJ, Flaig TW, Milowsky MI, et al. Enfortumab vedotin plus pembrolizumab in previously untreated advanced urothelial cancer. 

Published online August 30, 2022. doi:10.1200/JCO.22.01643

3. Seagen, Astellas and Merck Announce Results of Clinical Trial Investigating PADCEV (enfortumab vedotin-ejfv) with KEYTRUDA (pembrolizumab) and PADCEV as Monotherapy in First-Line Advanced Urothelial Cancer. News release. Seagen Inc/Astellas Pharma Inc/Merck. September 12, 2022. Accessed September 12, 2022. https://bwnews.pr/3xguTqr

The combination of enfortumab vedotin plus pembrolizumab led to a confirmed overall response rate of 64.5% in patients with metastatic urothelial cancer.

Enfortumab Plus Pembrolizumab Displays High ORR in Metastatic Urothelial Cancer

In a phase 3 trial evaluating perioperative nivolumab (Opdivo) in patients with renal cell carcinoma (RCC) at high risk for recurrence did not show improved recurrence-free survival (RFS), although various analyses within the trial may help to inform future research.

The study was presented at the 2022 European Society for Medical Oncology Congress in Paris, France.

“Given the success of nivolumab in improving outcomes in metastatic renal cell carcinoma, there is tremendous enthusiasm for expanding the use of immunotherapy in those with early-stage disease at risk for recurrence,” explained lead investigator Mohamad Allaf, MD, urologist-in-chief and The Johns Hopkins Hospital Professor of Urology, Johns Hopkins University, Baltimore, Maryland.

The study population included patients with RCC with tumors greater than 7 cm or patients with smaller renal tumors with venous fat or nodal involvement. Patients with low-volume M1 disease were also included “provided it was completely resected within 12 weeks of enrollment,” Allaf said.

The study’s primary end point was RFS, which the investigators defined as time from randomization to disease recurrence or death, whichever came first. Secondary end points included overall survival, RFS for clear cell RCC, safety and tolerability, patient-reported outcomes, and correlative science.

A total of 819 patients were enrolled in the study, 404 of whom were randomly assigned to receive surgery/nivolumab of 415 to surgery/observation. In the surgery/nivolumab arm, 353 patients started neoadjuvant nivolumab, 359 received surgery, and 314 started adjuvant nivolumab. In the surgery/observation arm, 387 patients underwent surgery. Patients were closely matched by age and gender. 

Thirty-one patients in the surgery/nivolumab arm were Black or African American vs 30 in the surgery/observation arm, and 332 patients in the surgery/nivolumab arm were White compared with 340 in the surgery/observation arm. Approximately 50% of patients enrolled had cT1/cT2 disease, approximately 15% had cN1 disease, and approximately 3% had cM1. Approximately 75% of patients had an ECOG performance status of 0.

Post surgery, more than 60% of patients had pT3/pT4 tumors, and more than 60% had high-grade tumors. Approximately 80% of patients had clear cell RCC and approximately 5% of patients in each group underwent partial nephrectomy.

Allaf explained that a preplanned futility analysis was based on recurrence and death events.

“At approximately 71% full information time, inefficacy analysis results were presented to the Data Safety Monitoring Committee, and it was recommended that the results be released for futility,” Allaf said.

At a median follow-up of 16 months, there was no difference in RFS between the 2 groups (HR: 0.97 [95% CI: 0.74-1.28], one-sided 

“OS was not mature at the time of analysis but was not statistically different between study arms (HR: 1.48; 95% CI: [0.89 – 2.48], one-sided 

value=0.93),” the authors wrote in their abstract.

“In terms of adverse events [AEs], the observed adverse event rates and types were fairly comparable to what is seen in other nivolumab monotherapy trials,” Allaf said. Ninety-three percent of patients in the surgery/nivolumab arm experienced an AE of any grade compared with 59% in the surgery/observation arm. Thirty-three percent of patients in the surgery/nivolumab arm experienced an AE of grade 3-4 as the highest grade vs 13% of patients in the surgery/observation arm. Treatment-related AEs with incidence greater than 10% included fatigue, abdominal pain, nausea, increased creatinine, pruritus, masculo-papular rash, diarrhea, arthralgia, increased alanine aminotransferase, increased aspartate aminotransferase, and hypothyroidism.

In his concluding remarks, Allaf said, “Perioperative nivolumab did not improve RFS in patients with renal cell carcinoma at high risk for recurrence in this trial…Ongoing radiomic, pathomic, and other biomarkers analyses within this trial may inform the design of future neoadjuvant renal cell carcinoma trials. Lastly, further analysis of patient subsets with this unique trial should help inform future research.”

1. Allaf M, Kim SE, Harshman LC, et al. Phase III randomized study comparing perioperative nivolumab (nivo) versus observation in patients (Pts) with renal cell carcinoma (RCC) undergoing nephrectomy (PROSPER, ECOG-ACRIN EA8143), a National Clinical Trials Network trial. 

2022;33(suppl 7):LBA67. doi:10.1016/annonc/annonc1089

Perioperative nivolumab in patients with RCC, at high risk for recurrence, did not see an improved RFS, but analyses within the phase 3 trial could inform future research. 

Improved Recurrence-Free Survival is not Seen with Perioperative Nivolumab in RCC

Darolutamide (Nubeqa) demonstrated a significantly reduced risk of metastatic progression and improved overall survival vs placebo when used as treatment for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), according to findings from a recent study presented at the 2022 American Society of Clinical Oncology Annual Meeting.

Previously reported findings of the phase 3 ARAMIS trial (NCT02200614) found that treatment with darolutamide significantly prolonged metastasis-free survival by nearly 2 years and reduced the risk of death by 31% vs placebo with favorable tolerability in patients with nmCRPC.

For the current study, the investigators, led by Alicia K. Morgans, MD, MPH, a genitourinary medical oncologist and the medical director of the Survivorship Program at Dana-Farber Cancer Institute in Boston, Massachusetts, conducted post hoc analyses of ARAMIS “evaluate the association between metastatic progression with prostate-specific antigen (PSA) and clinical progression and to describe the distribution of metastatic progression between groups,” according to the study’s abstract.

The investigators randomized patients 2:1 to darolutamide 600 mg twice daily or placebo while continuing treatment with androgen deprivation therapy. They performed descriptive analyses using the primary data cutoff for the double-blind period. Central review of conventional radiographic imaging every 16 weeks was used to determine post-baseline metastases.

The investigators observed metastatic progression in 130/955 patients treated with darolutamide (13.6%) vs 158/554 patients treated with placebo (28.5%). In the darolutamide arm, 46% of metastatic progression was bone only, 32% was distant lymph node only, and 22% was mixed metastatic types. In the placebo arm, 39% of metastatic progression was bone only, 40% was distant lymph node only, and 21% was mixed metastatic types.

Median time from initial diagnosis to study treatment was shorter in patients with metastatic progression (darolutamide arm, 86.2 months; placebo arm, 74.4 months) compared with the overall ARAMIS study population (86.2 and 84.2 months, respectively). For patients with metastatic progression, median PSA levels at baseline were similar between the 2 groups at 12.6 ng/mL in the darolutamide arm vs 15.1 ng/mL but were lower in the darolutamide patients before metastasis at 16.7 ng/mL compared with patients receiving placebo (48.0 ng/mL).

“Among patients with metastatic progression, PSA progression before metastasis occurred in 55.6% (160/288) of patients, occurring in fewer darolutamide vs placebo patients (45.4% vs 63.9%),” wrote the investigators in their poster.

In addition, the median time between PSA progression and metastasis was 7.0 months for darolutamide compared with 5.6 months for placebo. Pain progression before metastasis was 16.9% and 17.7% for the darolutamide and placebo arms, respectively.

“In patients with nmCRPC, darolutamide significantly reduced the risk of metastatic progression and improved overall survival compared with placebo without changing the pattern of metastatic progression….These results support the use of both imaging PSA monitoring to properly identify disease progression in patients with nmCRPC,” wrote the investigators in their conclusion.

1. Morgans AK, Sweeney C, Wallis CJD, et al. Progression patterns by types of metastatic spread, prostate-specific antigen (PSA), and clinical symptoms: Post-hoc analyses of ARAMIS. 

 2022;40(suppl 16):5044. doi:10.1200/JCO.2022.40.16_suppl.5044

2. Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. 

 2019;380(13):1235-1246. doi:10.1056/NEJMoa1815671

3. Fizazi K, Shore N, Temmela TL, et al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. 

 2020;383(11):1040-1049. doi:10.1056/NEJMoa2001342.

Reduced risk of metastatic progression and improved overall survival seen with darolutamide in patients with nonmetastatic castration-resistant prostate cancer.

Reduced Risk of Metastatic Progression With Darolutamide in Patients With nmCRPC

In a phase 2 clinical trial, the use of maintenance cabozantinib (Cabometyx) following chemotherapy in patients with advanced urothelial carcinoma demonstrated tolerability but did not show a significant benefit vs placebo.

Findings from the randomized, double-blind phase 2 ATLANTIS clinical trial were presented by first author Robert J. Jones, MA, PhD, MBChB, at the 2022 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.

The ATLANTIS trial included patients with advanced urothelial carcinoma who underwent 4 to 8 cycles of first-line chemotherapy, during which time they were prescreened for tissue-based biomarkers. Patients with ongoing clinical benefit after chemotherapy were offered randomization into one of several substudies based on biomarker status. Patients with a DNA repair deficiency were randomized to rucaparib (Rubraca) vs placebo, patients who were androgen receptor biomarker positive were randomized to enzalutamide (Xtandi) vs placebo, and patients who were “all biomarkers negative” received cabozantinib or placebo.

Patients in the cabozantinib arm received 40 mg once daily vs matching placebo. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), confirmed response rates, and safety and tolerability.

Recruitment was discontinued after 61 patients were randomized due to a United Kingdom-wide recruitment hiatus beginning in March 2020 because of the COVID-19 pandemic, and also due to the presentation of data in June 2020 supporting the use of avelumab (Bavencio) in the maintenance setting.2 The trial’s power was subsequently revised to 72.3% from an original value of 90%.

Jones reported a median PFS of 13.7 weeks (80% CI, 12.1-23.3) with cabozantinib vs 15.8 weeks (80% CI, 11.3-23.6) with placebo. The HR was 0.89 in favor of cabozantinib (80% CI, 0.61-1.30, 1-sided 

= .35). Median OS was 75.5 weeks (80% CI, 43.4-117.6) with cabozantinib vs 82.9 weeks (80% CI, 58.0-117.1) with placebo. The HR was 0.80 in favor of cabozantinib (80% CI, 0.52-1.30, 1-sided 

Median duration of treatment was 13 cycles for cabozantinib vs 10 cycles for placebo. Overall response rate was 3.3% for cabozantinib vs 6.5% for placebo.

Regarding safety, adverse events seen more commonly in patients receiving cabozantinib vs placebo included fatigue (56.7% vs 32.2%, respectively; 

 = .02), hypertension (43.3% vs 12.9%; respectively, 

 =.01), nausea (30% vs 19.4%, respectively; 

= .36) and diarrhea (40.0% vs 6.5%; respectively, 

“Notably, 43% of patients receiving cabozantinib had to reduce the dose from 40 to 20 mg, although there were no treatment discontinuations due to toxicity,” said Jones, professor of clinical research at the University of Glasgow Institute of Cancer Sciences in Glasgow, Scotland.

In his concluding remarks, Jones said, “Though underpowered, this study does not support further investigation of cabozantinib alone as a maintenance therapy after platinum-based chemotherapy in unselected patients with advanced urothelial cancer.”

Jones added that negative patient selection for DNA repair deficiency and androgen receptor biomarkers may have biased interpretation of the findings.

“Future trials should consider combining novel agents with maintenance immunotherapy,” Jones said.

1. Jones RJ, Hussain SA, Birtle AJ, et al. A randomised, double blind, phase II clinical trial of maintenance cabozantinib following chemotherapy for metastatic urothelial carcinoma (mUC): Final analysis of the ATLANTIS cabozantinib comparison. 

. 2022;40(suppl 170):LBA4505. doi:10.1200/JCO.2022.40.17_suppl.LBA4505

2. Powles T, Park SH, Voog E, et al. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. 

. 2020;383(13):1218-1230.doi:10.1056/NEJMoa2002788

Maintenance Cabozantinib Fails to Show Significant Benefit in Advanced Urothelial Carcinoma

The use of adjuvant pembrolizumab as treatment of patients with renal cell carcinoma (RCC) who are at high risk of recurrence continued to demonstrate improved disease-free survival (DFS) compared with placebo, according to an updated analysis of the phase 3 KEYNOTE-564 trial (NCT03142334).

The findings were reported by Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School in Boston, Massachusetts during the 2022 Genitourinary Cancers Symposium in San Francisco, California.

Previously reported data from KEYNOTE-564 found that treatment with adjuvant pembrolizumab yielded a statistically significant and clinically meaningful DFS benefit versus placebo in the intent-to-treat population (HR, 0.68, 95% CI: 0.53-0.87, 

= .001).2 The 2022 GU Symposium presentation consisted of an updated efficacy and safety analysis with 30.1months of follow-up.

KEYNOTE-564 evaluated patients with RCC defined as intermediate-high risk (pT2, grade 4 or sarcomatoid, N0, M0; pT3, any grade, N0, M0), high-risk (pT4, any grade, N0, M0; any pT, any grade, N+, M0) and M1 no evidence of disease (NED) following surgery. Patients randomized 1:1 to receive either pembrolizumab, 200 mg every 3 weeks (n = 496) or placebo every 3 weeks (n = 498).

Median patient age was 60 years in both the treatment and placebo groups. A total of 347 patients in the pembrolizumab group were male (70.0%) versus 359 patients (72.1%) in the placebo group. Regarding risk category, 427 patients were intermediate-high risk (86.1%), 40 patients (8.1%) were high risk, and 29 patients (5.8%) were M1 NED in the treatment group versus 433 (86.9%), 36 (7.2%), and 29 (5.8%) in the placebo group, respectively. In the treatment group, there 52 patients (10.5%) in whom sarcomatoid features were present versus 414 patients (83.5%) in whom sarcomatoid features were absent, compared with 59 (11.8%) and 415 (83.3%) in the placebo group.

For the primary end point of DFS, benefit was maintained in patients receiving pembrolizumab (HR, 0.63, 95% CI: 0.50-0.80, nominal 

< .0001) and was as follows across the 3 subgroups

Intermediate-high risk: HR, 0.68 (95% CI: 0.52-0.89)

“The estimated DFS rate at 24 months was 78.3% with pembrolizumab versus 67.3% with placebo…The estimated [overall survival] rate at 24 months was 96.2% with pembrolizumab versus 93.8% with placebo,” wrote the authors.

In the primary analysis of KEYNOTE-564, presented at 24.1 months’ follow-up, 470 patients (96.3%) in the pembrolizumab group experienced an all-cause adverse event (AE) versus 452 (91.1%) in the placebo arm; in the updated findings presented at the 2022 ASCO GU Symposium, the number of patients in the pembrolizumab arm experiencing an all-cause AE was unchanged compared with 453 patients (91.3%) in the placebo arm. Grade 3-4 AEs were also very similar for the pembrolizumab arm at 24.1 months and 30.1 months with 42 patients (8.6%) and 43 patients (8.8%) respectively, compared with 3 patients (0.6%) in the placebo arm at 24.1 and 30.1 months.

“I think that this updated analysis of KEYNOTE-564 further supports adjuvant pembrolizumab as a new standard of care for patients with RCC with high risk of recurrence,” Choueiri told 

1. Choueiri TK, Tomczak P, Park SH, et al. Pembrolizumab as post nephrectomy adjuvant therapy for patients with renal cell carcinoma: Results from 30-month follow-up of KEYNOTE-564. J Clin Oncol. 2022;40(suppl 6):abstr 290. doi:10.1200/JCO.2022.40.6_suppl.290

2. Choueiri TK, Tomczak P, Park SH, et al. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021;385(8):683-694. doi:10.1056/NEJMoa2106391

Updated findings from the phase 3 KEYNOTE-564 trial may further support adjuvant pembrolizumab as a new standard of care for patients with renal cell carcinoma with high risk of recurrence.