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Genitourinary Cancer

Relevant Articles About Research and Clinical Trials in Genitourinary Cancer

RELATED :Bladder Cancer:Prostate Cancer:RCC (Renal Cell Carcinoma)

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RCC (Renal Cell Carcinoma)Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibodyBevacizumabsunitinibCompletedCzechiaFranceGermanyItalyPolandRomaniaSpainUnited KingdomUnited States 0NCT01984242Phase 2IMmotion150
A Study of Atezolizumab (an Engineered Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) as Monotherapy or in Combination With Bevacizumab (Avastin®) Compared to Sunitinib (Sutent®) in Participants With Untreated Advanced Renal Cell Carcinoma

A Study of Atezolizumab (an Engineered Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) as Monotherapy or in Combination With Bevacizumab (Avastin®) Compared to Sunitinib (Sutent®) in Participants With Untreated Advanced Renal Cell Carcinoma

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PSA-Independent Radiographic Progression in mHSPC

KEY TAKEAWAYS

  • The ENZAMET phase 3 trial aimed to investigate the impact of enzalutamide, focusing on radiographic progression without PSA in mHSPC.
  • Researchers observed worse overall survival in mHSPC participants with radiographic progression without prior PSA progression.

ENZAMET, a randomized trial comparing enzalutamide (ENZA) to a standard non-steroidal anti-androgen (NSAA) in 1125 metastatic hormone-sensitive prostate cancer (mHSPC) participants, demonstrated superior PFS and OS with ENZA. Radiographic progression without prior/concurrent PSA progression (rProg1st) is an emerging biomarker of poor clinical outcomes. Ian D. Davis and his team aimed to determine its frequency and assess enzalutamide’s impact on disease state transition for the ENZAMET cohort.

Researchers used a multi-state Cox proportional hazards regression model to perform an inclusive analysis on the ENZAMET dataset. This model categorized participants into four states: (1) Evt-Free (event-free), (2) rProg1st (radiologic progression without confirmed PSA progression), (3) OtherProg (All Other types of clinical progression events (PSA and treatment switch, excluding death), (4) Death. 

Radiographic progression was documented in 34% (388/1125) of participants, with 10% (114/1125) experiencing radiographic progression without confirmed prior/concurrent PSA progression according to the protocol. Among them, 48% (55/114) were assigned ENZA and 52% (59/114) NSAA. Baseline characteristics of the 114 participants with rProg1st were comparable to the overall ENZAMET cohort and showed no significant differences between ENZA and NSAA groups. ENZA exhibited a delay in both rProg1st (HR 0.66, 95%CI: 0.46 to 0.96, P=0.03) and OtherProg (HR 0.37, 95%CI: 0.31 to 0.44, p<0.001) compared to NSAA. The 5-year OS rates were 24% (95%CI: 18-34) in the rProg1st group versus 42% (95%CI: 38-47) in the OtherProg group. Among those who had not progressed (495/1125) with a median follow-up of 68 months, 8% died from causes unrelated to prostate cancer. As previously reported, ENZA extended overall survival in the entire trial cohort (N=1125, HR 0.70, 95%CI 0.58 to 0.84, P<0.0001).

The study concluded that participants experiencing radiographic progression without prior/concurrent PSA progression demonstrated worse overall survival, irrespective of NSAA or enzalutamide assignment. Enzalutamide significantly reduced hazards and delayed the onset of both rProg1st and OtherProg. Despite the absence of identifiable baseline characteristics, the study advocates for future molecular biological analyses to facilitate early identification of this unique subgroup.

The Study is sponsored by University of Sydney

Source: https://meetings.asco.org/abstracts-presentations/230122

Clinical Trail: https://clinicaltrials.gov/study/NCT02446405

Davis. I D, Martin A J, Zielinski R R, et.al (2024). “Radiographic progression without PSA progression in metastatic hormone-sensitive prostate cancer (mHSPC): A retrospective analysis from the ENZAMET trial (ANZUP 1304).” Presented at ASCO GU 2024 (Abstract 151). 

 

Neoadjuvant NIVO & Nab-ABX in MIBC: NURE-Combo Study

KEY TAKEAWAYS

  • The NURE-Combo phase 2 trial aimed to investigate the efficacy and safety of neoadjuvant NIVO combined with nab- ABX, followed by RC and adjuvant NIVO in patients with MIBC.
  • The primary endpoint was to determine PCR.
  • Researchers concluded that the NURE-Combo trial demonstrated the potential effectiveness and safety of the novel chemo-immunotherapy combination NIVO+ABX in MIBC patients.

Muscle-invasive bladder cancer (MIBC) is a systemic disease with a high recurrence risk post-radical cystectomy (RC), the standard of care (SOC) for cisplatin-ineligible patients. Preliminary findings indicate nab-paclitaxel (ABX’s) activity in combination with pembrolizumab for advanced urothelial carcinoma. Chiara Mercinelli and her team aimed to present the phase 2 trial results of neoadjuvant nivolumab (NIVO + ABX) followed by RC and adjuvant NIVO in MIBC patients.

Researchers conducted an inclusive analysis involving eligible patients unfit for cisplatin or those who declined cisplatin-based treatment with previously untreated MIBC meeting clinical criteria (T2-T4a, N0-1, M0 via CT and MRI scan). Criteria included Eastern Cooperative Oncology Group performance status ≤ 1 and predominant (> 50%) urothelial carcinoma histology. Patients underwent 4 cycles of NIVO 360 mg Q3W + ABX 125 mg/m2 on Day 1 and 8, Q3W, followed by RC. Adjuvant NIVO was administered for 13 cycles. The primary endpoint was the pathologic complete response (pCR) rate ypT0N0; H0: ≤20% and H1≥ 38% in a 2-stage design: ≥9 ypT0N0 were required in stage 1+2). Secondary endpoints encompassed major pathological response (ypT≤1N0), safety (CTCAE v5.0), and event-free survival (EFS). Tumor biomarkers included comprehensive genomic profiling (CGP), PD-L1 expression, and circulating tumor DNA monitoring (Signatera).

About 31 patients were enrolled in the study between December 2021 and June 2023, with 17 (54.8%) at cT3-4 stage, 14 (45.2%) at cT2, 2 (6.4%) at N1 stage, and 15 (48.4%) exhibiting variant histology. All 31 patients completed neoadjuvant treatment, and as of the data cutoff, 29 showed pathological responses. 4 patients (14.8%) received <4 cycles due to treatment-related adverse events (TRAEs), with 4 experiencing G3 TRAEs, including neutropenia (2), asthenia (1), increased AST/ALT (2), neurotoxicity (1), and acute renal failure (1). The median time from treatment start to RC was 4 months (IQR: 3-4).

A total of 11 patients (38%; 95%CI 20.3-55.6) achieved ypT0N0 response, and 21 (72%; 95%CI 55.3-88.3) achieved ypT≤1N0 response. No disease progressions (PD) occurred during neoadjuvant treatment. After a median 10.6 months follow-up (IQR: 8-16), only 1 patient experienced PD, resulting in a 12-month event-free survival (EFS) of 96.4% (95%CI: 89.9-100). The mean tumor mutational burden (TMB) was 12.3 mut/Mb for ypT0N0 responders versus 5.8 mut/Mb for non-responders. Notably, all patients with MRI complete response (CR) had a ctDNA-negative assay post neoadjuvant NIVO-ABX.

The study concluded that the Nure-Combo trial highlights the potential of the novel chemo-immunotherapy combination NIVO+ABX as an effective and safe perioperative strategy for MIBC patients, offering sustained efficacy post-RC. These findings may broaden the scope of chemotherapy combinations for cisplatin-ineligible patients and underscore the significance of clinical CR in advocating for organ-sparing approaches.

The Study is sponsored by IRCCS San Raffaele

Source: https://meetings.asco.org/abstracts-presentations/229753

Clinical Trail: https://clinicaltrials.gov/study/NCT04876313

Mercinelli C, Basile G, Raggi D,  et.al (2024).”First results of NURE-Combo: A phase 2 study of neoadjuvant nivolumab (NIVO) and nab-paclitaxel (ABX) followed by postsurgical adjuvant NIVO in patients (pts) with muscle-invasive bladder cancer (MIBC).” Presented at ASCO GU 2024 (Abstract 610). 

PSA-Independent Radiographic Progression in mHSPC

KEY TAKEAWAYS

  • The ENZAMET phase 3 trial aimed to investigate the impact of enzalutamide, focusing on radiographic progression without PSA in mHSPC.
  • Researchers observed worse overall survival in mHSPC participants with radiographic progression without prior PSA progression.

ENZAMET, a randomized trial comparing enzalutamide (ENZA) to a standard non-steroidal anti-androgen (NSAA) in 1125 metastatic hormone-sensitive prostate cancer (mHSPC) participants, demonstrated superior PFS and OS with ENZA. Radiographic progression without prior/concurrent PSA progression (rProg1st) is an emerging biomarker of poor clinical outcomes. Ian D. Davis and his team aimed to determine its frequency and assess enzalutamide’s impact on disease state transition for the ENZAMET cohort.

Researchers used a multi-state Cox proportional hazards regression model to perform an inclusive analysis on the ENZAMET dataset. This model categorized participants into four states: (1) Evt-Free (event-free), (2) rProg1st (radiologic progression without confirmed PSA progression), (3) OtherProg (All Other types of clinical progression events (PSA and treatment switch, excluding death), (4) Death. 

Radiographic progression was documented in 34% (388/1125) of participants, with 10% (114/1125) experiencing radiographic progression without confirmed prior/concurrent PSA progression according to the protocol. Among them, 48% (55/114) were assigned ENZA and 52% (59/114) NSAA. Baseline characteristics of the 114 participants with rProg1st were comparable to the overall ENZAMET cohort and showed no significant differences between ENZA and NSAA groups. ENZA exhibited a delay in both rProg1st (HR 0.66, 95%CI: 0.46 to 0.96, P=0.03) and OtherProg (HR 0.37, 95%CI: 0.31 to 0.44, p<0.001) compared to NSAA. The 5-year OS rates were 24% (95%CI: 18-34) in the rProg1st group versus 42% (95%CI: 38-47) in the OtherProg group. Among those who had not progressed (495/1125) with a median follow-up of 68 months, 8% died from causes unrelated to prostate cancer. As previously reported, ENZA extended overall survival in the entire trial cohort (N=1125, HR 0.70, 95%CI 0.58 to 0.84, P<0.0001).

The study concluded that participants experiencing radiographic progression without prior/concurrent PSA progression demonstrated worse overall survival, irrespective of NSAA or enzalutamide assignment. Enzalutamide significantly reduced hazards and delayed the onset of both rProg1st and OtherProg. Despite the absence of identifiable baseline characteristics, the study advocates for future molecular biological analyses to facilitate early identification of this unique subgroup.

The Study is sponsored by University of Sydney

Source: https://meetings.asco.org/abstracts-presentations/230122

Clinical Trail: https://clinicaltrials.gov/study/NCT02446405

Davis. I D, Martin A J, Zielinski R R, et.al (2024). “Radiographic progression without PSA progression in metastatic hormone-sensitive prostate cancer (mHSPC): A retrospective analysis from the ENZAMET trial (ANZUP 1304).” Presented at ASCO GU 2024 (Abstract 151). 

 

Darolutamide + ADT Efficacy and Safety in HRLPC

Darolutamide + ADT Efficacy and Safety in HRLPC

KEY TAKEAWAYS

  • The phase 2 trial aimed to investigate the impact of neoadjuvant darolutamide combined with ADT in patients with HRLPC/VHRLPC undergoing RP.
  • The primary endpoint was to determine PRR and MRD.
  • Researchers noticed that neoadjuvant darolutamide plus ADT demonstrated improved clinical and pathological responses in men with HRLPC/VHRLPC.

Radical prostatectomy (RP) poses challenges with adverse surgical outcomes and heightened disease progression risks in high-risk/very high-risk localized prostate cancer (HRLPC/VHRLPC) patients. Junlong Zhuang and his team aimed to assess neoadjuvant darolutamide, a next-gen androgen receptor inhibitor, combined with androgen deprivation therapy (ADT) for RP in HRLPC/VHRLPC patients.

Researchers performed an inclusive analysis in a multicenter, single-arm phase II clinical trial involving patients aged 18-75 with HRLPC/VHRLPC, defined as Gleason ≥ 8 and/or cT3-4N0-1 and/or PSA ≥ 20 ng/mL. VHRLPC criteria included cT3b-cT4, primary Gleason pattern 5, 2 or 3 high-risk features, and > 4 cores with Grade Group 4 or 5. Eligible patients underwent a 6-month regimen of neoadjuvant darolutamide plus ADT followed by RP. 

The primary endpoint assessed was the pathological response rate, encompassing patients with pathologic complete response (pCR) or minimal residual disease (MRD). Secondary endpoints included safety, PSA progression-free survival (PFS), positive surgical margins rate, downstaging rate, and PSA response rate.

About 30 patients, all undergoing robotic-assisted RP, were enrolled. Median age was 71.0 years (IQR, 65.2-73.0), baseline PSA level was 37.8 ng/mL (IQR, 21.0-94.7). Predominantly, 93.3% had very high-risk localized prostate cancer (VHRLPC); 6.7% had HRLPC with 26.7% N1 disease, 86.7% cT3-4, 90% Gleason 8-10, and 77% PSA ≥ 20 ng/mL. Median prostate volume pre-RP was 19.4 mL (IQR, 15.6-28.4). Post-RP, 27 patients (90%) had undetectable PSA levels (<0.01 ng/mL). Pathological response rate was 40.0%, with 6.7% pCR and 33.3% MRD rates. Downstaging was achieved in 20 patients (66.7%), and positive surgical margins occurred in only 13.3%. The extracapsular extension was noted in 11 patients (36.6%) of cases. 

The study concluded that preoperative administration of darolutamide plus ADT for 6 months significantly enhanced clinical and pathological responses in men with HRLPC/VHRLPC. Furthermore, the intervention demonstrated a favorable safety profile. 

The study is sponsored by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Source: https://meetings.asco.org/abstracts-presentations/230315

Clinical Trial: https://clinicaltrials.gov/study/NCT05249712

Zhuang J, Wang Y, Zhang S, et al. (2024). “Neoadjuvant darolutamide plus androgen deprivation therapy for high-risk/very high-risk localized prostate cancer: A multicenter, open-labeled, single-arm phase II trial.”  Presented at ASCO-GU 2024 (Abstract 321).

Pem + Cabo: 1L Therapy for Cisplatin-Ineligible mUC

KEY TAKEAWAYS

  • The PemCab phase 2 trial aimed to investigate the safety and efficacy of the Pem + Cabo as a 1L therapy for treating mUC pts.
  • The primary endpoint was to determine ORR, and the secondary endpoints were to determine PFS and OS.
  • Researchers noticed a manageable toxicity profile and promising efficacy of Pem + Cabo for 1L therapy in mUC pts; further investigation is ongoing.

Pembrolizumab (pem) was initially approved for first-line (1L) treatment of metastatic urothelial carcinoma (mUC) in cisplatin-ineligible patients (pts) with high PD-L1 expression and platinum-ineligible pts regardless of PD-L1 status. However, subsequent revisions restricted its approval to only platinum-ineligible pts, and pem monotherapy exhibited a notable high disease progression (PD) rate. Cabozantinib (cabo), a receptor tyrosine kinase inhibitor targeting MET and VEGFR2, has shown efficacy in various malignancies as monotherapy or in combination with PD-1 inhibition. Rohit K. Jain and his team aimed to assess that combining pem and cabo would offer a safe and efficacious 1L therapy for treatment-naïve mUC pts.

They performed an inclusive analysis within a phase II, open-label, multi-center, single-arm trial assessing the tolerability and activity of pem at 200 mg every 3 weeks and cabo at 40 mg daily as first-line treatment for pts with mUC. The trial enrolled pts with histologically proven locally advanced or mUC, an ECOG-PS of 0-2, cisplatin ineligibility (including patient refusal of cisplatin), treatment naivety, and no prior PD-1/L1 therapy.

The primary endpoint was the objective response rate (ORR), with key secondary endpoints  including progression-free survival (PFS) and overall survival (OS). A lead-in safety cohort of 6 pts was incorporated. The hypothesis posited that the combination therapy would enhance the ORR to > 32%. With 35 evaluable subjects, the lower bound of the 95% CI was expected to extend no more than 26% from the observed proportion. The criterion for success was achieving ≥17 objective responses, ensuring the CI excluded 32%.

About 36 pts were enrolled between December 26, 2018, and April 19, 2023, with 35 evaluated for response, representing a median follow-up of 14.4 months (95% CI 12.2 – 16.2). The cohort exhibited a median age of 72.5 years (range 47-82), with 89% of pts having an ECOG PS of 0-1. Notably, 15 pts demonstrated responses (ORR= 42.8%), including 5 complete responses (14.3%), while stable disease was observed in 10 pts (28.6%). The disease control rate (DCR) reached 68.5% (25/35). Median PFS was calculated at 7.7 months (95% CI 4.2 – 11.2).

Regarding treatment-related adverse events (TRAE), 52% of pts developed any grade events attributable to either cabo or pem. The most common grade 1/2 TRAEs encompassed diarrhea, anorexia, dysgeusia, weight loss, and nausea. Further, 44% of pts experienced grade 3/4 TRAEs, with the most frequent occurrences being hypertension, hypophosphatemia, alanine transaminase elevation, diarrhea, and fatigue.

The study concluded that the novel phase II trial of Pem + Cabo exhibited a manageable toxicity profile and promising efficacy in first-line therapy for mUC, even in pts ineligible for cisplatin. Ongoing investigations prioritize further exploration of predictive biomarkers to enhance treatment precision and outcomes in this patient population.

The study is sponsored by University of Utah 

Source: https://meetings.asco.org/abstracts-presentations/230644

Clinical Trial: https://clinicaltrials.gov/study/NCT03534804

Jain R K, Swami U, Bilen M A, et al (2024). “Cabozantinib plus pembrolizumab as first-line therapy for cisplatin-ineligible advanced urothelial carcinoma (PemCab).” Presented at ASCO- GU 2024 (Abstract 539).

Abiraterone Combo In HRRm McRpc Patients: BRCAAway

KEY TAKEAWAYS

  • The Phase 2 trial aimed to investigate the efficacy of AR-inhibitor (i) vs PARPi as 1L treatment in mCRPC pts.
  • The primary endpoint was to determine PFS, clinical assessment, or death.
  • Researchers noticed that in mCRPC pts with BRCA1/2 or ATM alterations, the combination of abiraterone/prednisone + olaparib demonstrated superior tolerability PFS.

Deleterious germline or somatic homologous recombination-repair mutations (HRRm) are observed in approximately 20% of metastatic castration-resistant prostate cancer (mCRPC) patients (pts). Previous preclinical studies have indicated synergistic effects between PARP inhibition and androgen receptor (AR)–targeted therapy. The BRCAAway was designed as a pre-selected biomarker in a multicenter, randomized phase-2 study.

Maha H. A. Hussain and her research team aimed to evaluate the efficacy of AR inhibitor (i) alone, PARP inhibitor (PARPi) alone, or their combination as the first-line treatment for mCRPC pts harboring germline and/or somatic mutations in BRCA1/2 or ATM.

Researchers performed an inclusive analysis to assess eligibility criteria for the BRCAAway trial, focusing on front-line mCRPC pts without prior exposure to poly (ADP-ribose) polymerase inhibitors (PARPi), androgen receptor inhibitors (ARi) or chemotherapy for mCRPC. Additionally, participants underwent a washout period for antiandrogen, radiation, and other investigational agents. Eligible pts underwent tumor next-generation sequencing (NGS) and germline testing, with those exhibiting inactivating BRCA1/2 and/or ATM alterations randomized in a 1:1:1 ratio to receive Arm I (abiraterone 1000 mg qd + prednisone 5mg bid), Arm II (olaparib 300 mg bid), or Arm III (olaparib + abiraterone/prednisone).

The primary endpoint of the study was progression-free survival (PFS), evaluated as per RECIST 1.1, PCWG3 criteria, clinical assessment, or death. Secondary endpoints encompassed measurable disease response rate (RR), prostate-specific antigen response rate (PSA RR), and toxicity assessment. Arm I and II pts could cross over at progression.

About 165 pts were initially registered and underwent NGS and germline testing; subsequently, 61 pts with HRRm were randomized into Arms I-III. The median age of the cohort was 67 years (range 42-85), with 55 individuals identified as White and 6 as Black. Prior treatment history revealed 26% of pts had received Docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC), and 3.3% had received Darolutamide/Enzalutamide for non-metastatic castration-resistant prostate cancer (nmCRPC).

Disease site distribution included bone n=44 pts, viscera n=12, lymph nodes n=31, and n=3 in other locations. The median baseline prostate-specific antigen PSA: 14 ng/ml (range 0.15-4,037 ng/ml). HRRm status distribution comprised BRCA1 n=3, BRCA2 n=46, ATM n=11, multiple n=1 (33 germline, 28 somatic).

The median (range) time from randomization to the last encounter for pts still alive was =56: 16 (0.8-60), 15 (4.1-36), and 23 (2.9-56) months (m) in Arms I, II, and III, respectively. Treatment-related adverse events (AEs) were reported in 51 pts, with the most common Grade 3: fatigue n=3, anemia n=2, and ALT increases n=2.

Overall survival (OS) data were not yet mature, with 3 deaths in Arm I and 2 in Arm II. 8/19 pts in Arm I and 8/21 in Arm II crossed over from abiraterone to olaparib or vice versa at progression. Median (95% CI) PFS from crossover to olaparib 8.3 months (5.5, 15) and to abiraterone was 7.2 months (2.8, NR). Median (95% CI) PFS from randomization: olaparib 16 m (7.8-25) and abiraterone 16 m (11-28). RR to crossover treatment: olaparib 38% and abiraterone 25%. PSA RR to crossover treatment: olaparib 50% and abiraterone 63%.

The study concluded that in mCRPC pts with BRCA1/2 or ATM alterations, the combination of abiraterone/prednisone + olaparib demonstrated favorable tolerability and significantly extended PFS compared to using either agent alone or sequentially.

The study is sponsored by Northwestern University

Source: https://meetings.asco.org/abstracts-presentations/230557

Clinical Trial: https://clinicaltrials.gov/study/NCT03012321

Hussain M H A, Kocherginsky M, Agarwal N, et al. (2024). “BRCAAway: A randomized phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) bearing homologous recombination-repair mutations (HRRm).” Presented at ASCO-GU 2024 (Abstract 19).

Pembro vs Observation in Bladder Cancer and MIUC

KEY TAKEAWAYS

  • The AMBASSADOR study, phase 3 trial, aimed to investigate the efficacy of pembro as adjuvant therapy post-surgical resection in high-risk MIUC pts.
  • The primary endpoints were to determine DFS and OS.
  • Researchers noticed a significant improvement in DFS with adjuvant pembro over obs in high-risk MIUC pts; further information will be provided later.

Muscle-invasive urothelial carcinoma (MIUC) presents a formidable clinical challenge characterized by its aggressive nature and propensity for high relapse rates. The established standard of care involves neoadjuvant platinum-based chemotherapy (NAC), primarily in patients (pts) eligible for cisplatin (Cis). However, a considerable subset of pts is deemed Cis-ineligible or experiences persistent muscle-invasive disease following NAC and subsequent surgery.

Andrea B. Apolo and her team aimed to address the limitations in the current treatment paradigm by evaluating the potential of pembrolizumab (pembro) as adjuvant therapy for pts with high-risk MIUC following surgical resection.

Researchers performed an inclusive analysis as part of the AMBASSADOR study, an open-label, randomized, phase III trial. The study enrolled pts with histologically confirmed MIUC in the bladder, upper tract, or urethra. Eligible participants either exhibited ≥ pT2 and/or pN+ or margins+ at surgery after NAC or (2) ≥ pT3 and/or pN+ or margins+ at surgery without NAC, being either cisplatin (Cis)-ineligible or choosing to forego adjuvant Cis-based therapy. Registration occurred within  ≥4 to 16  weeks post-surgery, with a 1:1 randomization to receive pembro at 200 mg every 3 weeks for 1 year or observation (Obs) .

Randomization was stratified based on pathologic stage, centrally tested PD-L1 status, and prior NAC. The study’s dual primary endpoints were disease-free survival (DFS) and overall survival (OS), aiming for a target sample size of 739 pts. Final analysis required 387 DFS and 320 OS events. Secondary objectives included assessing DFS and OS in PD-L1-positive and -negative pts, along with safety evaluations. The interim results presented herein contribute to the ongoing understanding of the trial’s outcomes.

About 702 pts were randomized between 09/2017 and 08/2021 before early closure, prompted by the US FDA approval of nivolumab for MIUC pts. Of these, 354 pts were allocated to receive pembro, while 348 were assigned to Obs. A total of 13.0% and 21.6% withdrew from the study without an event in the Pembro and Obs arms, respectively. Notably, 74 pts (21%) in the Obs arm received an immune checkpoint inhibitor.

The median follow-up was 22.3 months for DFS and 36.9 months for OS. For DFS, based on 319 events needed for interim analysis, the efficacy boundary was crossed. The median DFS was 29.0 months (95% CI 21.8‒not evaluable [NE]) with Pembro compared to 14.0 months (95% CI 9.7‒20.20) with Obs. The HR was 0.69 (95% CI 0.55–0.87), demonstrating a statistically significant improvement with Pembro (p=0.0013).

In the interim analysis (n = 257 events) for OS, the median was 50.9 months (95% CI 43.9‒NE) with Pembro and 55.8 months (95% CI 53.3‒NE) with Obs. The HR for OS was 0.98 (95% CI 0.76–1.26), indicating no statistically significant difference between the two arms (p=0.88). Grade 3+ adverse events occurred in 48.4% of pts in the Pembro arm compared to 31.8% in the Obs arm. 

The study concluded that adjuvant pembro demonstrated a statistically significant and clinically meaningful improvement in DFS compared to obs for high-risk MIUC pts following radical surgery. The observed impact on overall survival (OS) may be influenced by pts in the obs arm receiving a checkpoint inhibitor. Pembro was well-tolerated, showing no new safety signals. These compelling results support the consideration of adjuvant pembro as a new therapeutic option for MIUC pts at high risk for recurrence. Ongoing additional follow-up will provide insights into the final outcomes for DFS and OS and specific analyses related to PD-L1 subgroups and circulating tumor DNA (ctDNA).

The study is sponsored by National Cancer Institute (NCI)

Source: https://meetings.asco.org/abstracts-presentations/229702

Clinical Trial: https://clinicaltrials.gov/study/NCT03244384

Apolo A B, Ballman K V, Sonpavde G P, et al. (2023). “AMBASSADOR Alliance A031501: Phase III randomized adjuvant study of pembrolizumab in muscle-invasive and locally advanced urothelial carcinoma (MIUC) vs observation.” Presented at ASCO-GU 2024 (Abstract LBA531).

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