📬 GU Oncology Intelligence Digest — Week 2026-W28

LITESPARK-022 belzutifan plus pembrolizumab published in NEJM with a 28% DFS improvement in adjuvant ccRCC, casdatifan ARC-20 lands in Nature, and ARTO shows an overall survival benefit for SBRT in oligometastatic CRPC.

⚡ TL;DR

📄 Publications

Adjuvant Pembrolizumab plus Belzutifan for Renal-Cell Carcinoma. — DFS significantly higher with pembrolizumab-belzutifan, HR 0.72 (95% CI 0.59-0.87), P<0.001; 24-month DFS 80.7% vs 73.7%
AI-Based Pathology classifier Predicts Sensitivity to Enzalutamide in Metastatic Hormone-Sensitive Prostate Cancer: A Biomarker Analysis of the ENZAMET Trial. — APIC-negative disease showed improved survival with enzalutamide (HR=0.50, 95%CI:0.35-0.73; 60-month OS 76.5% vs 58.3%), while APIC-positive showed limited benefit (HR=1.04)
SBRT plus abiraterone acetate and ADT versus abiraterone acetate and ADT in oligometastatic castrate-resistant prostate cancer (ARTO): long-term, unplanned overall survival analysis of an open-label, randomised, phase 2 trial. — Median OS 50 months in control versus NR in the experimental group (HR 0.55, 95% CI 0.33-0.92, p=0.021)

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Casdatifan ARC-20 in Nature: second HIF-2α inhibitor with pivotal-level activity in refractory ccRCC — Across 127 patients, confirmed ORR 31-35% and median PFS 12.2 months overall
LITESPARK-022: belzutifan plus adjuvant pembrolizumab published in NEJM for high-risk ccRCC — DFS HR 0.72 (95% CI 0.59-0.87), P<0.001; 24-mo DFS 80.7% vs 73.7%
CheckMate 214 final 9-year follow-up: durable survival with nivolumab plus ipilimumab in advanced RCC — Favorable-risk OS trend favors NIVO+IPI (HR 0.80); RCC-specific survival (HR 0.68) paralleled OS (HR 0.69)
EU approval of tumor-agnostic trastuzumab deruxtecan raises HER2 testing questions in urothelial cancer — EU approved Enhertu as the first tumor-agnostic HER2-directed ADC for previously treated HER2 IHC3+ metastatic solid tumors
ARTO long-term OS analysis: SBRT metastasis-directed therapy extends survival in oligometastatic CRPC — Median OS 50 months in control versus NR in experimental group (HR 0.55, 95% CI 0.33-0.92, p=0.021)

Full details below ↓

📄 What's Being Published

Manuscripts:

Adjuvant Pembrolizumab plus Belzutifan for Renal-Cell Carcinoma. — Choueiri Toni K et al., N Engl J Med

In the LITESPARK-022 trial, disease-free survival was significantly higher with pembrolizumab-belzutifan than with pembrolizumab-placebo (hazard ratio for disease recurrence or death, 0.72; 95% CI, 0.59 to 0.87; two-sided P<0.001), with estimated 24-month DFS of 80.7% versus 73.7%. Overall survival did not differ significantly at interim analysis (HR 0.78; 95% CI, 0.51 to 1.19; P=0.24). Grade 3 or higher adverse events occurred in 52.1% of participants receiving pembrolizumab-belzutifan versus 30.2% in the pembrolizumab-placebo group.

Clinical bottom line: Adding belzutifan to adjuvant pembrolizumab significantly improves disease-free survival in high-risk resected ccRCC but at the cost of substantially more grade 3+ toxicity, with overall survival still immature.

Read full article →

🔗 Also discussed on social media →

AI-Based Pathology classifier Predicts Sensitivity to Enzalutamide in Metastatic Hormone-Sensitive Prostate Cancer: A Biomarker Analysis of the ENZAMET Trial. — Medina Sebastian et al., Clin Cancer Res

In a biomarker analysis of the ENZAMET trial, APIC-negative disease showed improved survival with enzalutamide versus non-steroidal antiandrogen (HR=0.50, 95% CI: 0.35–0.73; 60-month OS 76.5% vs 58.3%), while APIC-positive disease showed limited evidence of benefit (HR=1.04, 95% CI: 0.67–1.62; 60-month OS 55.6% vs 58.8%). APIC significantly modified enzalutamide benefit, with an interaction p=0.014.

Clinical bottom line: A locked AI pathology classifier applied to ENZAMET confirms that APIC-negative mHSPC derives major overall survival benefit from enzalutamide, extending the CHAARTED-derived biomarker to a second phase 3 trial.

Read full article →

🔗 Also discussed on social media →

SBRT plus abiraterone acetate and ADT versus abiraterone acetate and ADT in oligometastatic castrate-resistant prostate cancer (ARTO): long-term, unplanned overall survival analysis of an open-label, randomised, phase 2 trial. — Francolini Giulio et al., Lancet Oncol

Between January 2, 2019, and September 7, 2022, 157 patients were randomly assigned to control (n=82) and experimental (n=75) groups. Median overall survival was 50 months (95% CI 36–not reached) in the control group versus not reached (95% CI 55–NR) in the experimental group (HR 0.55, 95% CI 0.33–0.92, p=0.021).

Clinical bottom line: Adding SBRT metastasis-directed therapy to abiraterone plus ADT delivers a significant overall survival benefit in oligometastatic castrate-resistant prostate cancer.

Read full article →

🔗 Also discussed on social media →

First-Line Enfortumab Vedotin Plus Pembrolizumab vs Gemcitabine Plus Cisplatin for Metastatic Urothelial Carcinoma. — Velasquez Eusebio Luna et al., JAMA Netw Open

In a real-world cohort of 4,433 patients (1,841 receiving EV/P and 2,592 receiving gemcitabine/cisplatin), first-line EV/P was associated with a lower risk of death (HR, 0.70; 95% CI, 0.63–0.79) and longer median OS (20 vs 11 months). EV/P was also associated with lower risk of event-horizon analysis (HR, 0.73; 95% CI, 0.64–0.83) and longer time to next treatment (median 35 vs 10 months; HR, 0.49; 95% CI, 0.39–0.61).

Clinical bottom line: Real-world data support EV/P over gemcitabine-cisplatin as first-line therapy for metastatic urothelial carcinoma, with longer overall survival and delayed time to next treatment.

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Clinically relevant endpoints and quality-of-life outcomes with darolutamide in patients with metastatic hormone-sensitive prostate cancer: Analyses of the phase III ARASENS trial. — Fizazi Karim et al., Eur J Cancer

In analyses of the phase III ARASENS trial, darolutamide significantly delayed time to mCRPC (HR 0.36, 95% CI 0.30–0.42) and time to pain progression (HR 0.79, 95% CI 0.66–0.95) versus placebo.

Clinical bottom line: Darolutamide triplet therapy delays time to castration resistance and pain progression while preserving quality of life, reinforcing it as a standard-of-care option in mHSPC.

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The impact of abiraterone and enzalutamide on hypokalemia incidence in patients with prostate cancer: a systematic review and meta-analysis. — Lou Yibo et al., BMC Cancer

A pooled meta-analysis demonstrated a significantly increased risk of all-grade hypokalemia in patients receiving androgen receptor axis-targeted therapies compared to controls (RR = 3.11, 95% CI: 1.88–5.15, P <0.001; I²=91.9%). This risk was significantly elevated with abiraterone (RR = 3.25, 95% CI: 1.75–6.02) and the combination of abiraterone plus enzalutamide (RR = 4.62, 95% CI: 2.65–8.03), but not with enzalutamide alone (RR = 1.16, 95% CI: 0.96–1.39).

Clinical bottom line: Abiraterone and abiraterone-enzalutamide combinations meaningfully raise the risk of hypokalemia in advanced prostate cancer, warranting proactive potassium monitoring.

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Clinical Validation of a Multiplex Urine Biomarker Assay for Surveillance of Recurrent Bladder Cancer. — Lotan Yair et al., Clin Cancer Res

In the validation cohort, Oncuria-Monitor achieved a sensitivity of 85.6% (95% CI: 78.1–92.2%) and a negative predictive value of 93.0% (95% CI: 89.2–96.4%). This performance enables a rule-out strategy that could safely reduce cystoscopy in approximately 25% of surveillance visits.

Clinical bottom line: A validated multiplex urine assay outperforms BladderChek and cytology and could safely spare a quarter of surveillance cystoscopies in recurrent bladder cancer.

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Comparison of [18F]DCFPyL and [18F]FAPI-74 PET/CT imaging in metastatic prostate cancer. — Hyväkkä Anniina et al., Eur J Nucl Med Mol Imaging

18F-DCFPyL PET/CT detected 1,351 lesions (99%), while 18F-FAPI-74 identified only 788 (58%) lesions in the PSMA-guided analysis and 523 (38%) lesions in the independent analysis. Median lesion SUVmax was higher for PSMA (24) than for FAPI (5.4) (p <0.001).

Clinical bottom line: PSMA PET/CT remains the preferred molecular imaging method in metastatic prostate cancer, with FAPI theranostics best reserved for visceral metastases and non-acinar histologies.

Read full article →

🗣️ What People Were Discussing This Week

How these are chosen: filtered for clinical relevance, grouped by the new development discussed, then ordered by engagement (bookmarks and reposts).

Casdatifan ARC-20 in Nature: second HIF-2α inhibitor with pivotal-level activity in refractory ccRCC

Across 127 patients in the ARC-20 study, casdatifan produced confirmed objective response rates of 31–35%, a disease control rate of 84%, and median progression-free survival of 12.2 months. Deeper serum EPO reductions and high HIF-2α protein expression (≥25% IHC) significantly correlated with PFS. Oncologists noted that casdatifan is the second HIF-2α inhibitor with enough activity to move to a pivotal study after belzutifan, and debate centers on whether EPO suppression and HIF-2α protein expression should become the operative biomarkers for patient selection ahead of the PEAK-1 phase 3 readout.

Discussed by: @DrChoueiri, @arcusbio, @weoncologists, @katy_beckermann

→ View representative tweet

LITESPARK-022: belzutifan plus adjuvant pembrolizumab published in NEJM for high-risk ccRCC

LITESPARK-022 is the first positive phase 3 trial combining HIF-2α inhibition with immunotherapy in the adjuvant setting: pembrolizumab plus belzutifan achieved a DFS HR of 0.72 (95% CI 0.59–0.87, P<0.001), with 24-month DFS of 80.7% versus 73.7% for pembrolizumab alone after nephrectomy for high-risk ccRCC. OS remains immature (HR 0.78, 95% CI 0.51–1.19, P=0.24), and grade ≥3 adverse events were substantially higher at 52.1% versus 30.2%. The central debate is whether the anemia burden and immature survival data support adding belzutifan across all high-risk ccRCC or only in the highest-risk and M1 NED patients.

Discussed by: @DrRishabhOnco, @DrChoueiri, @niklas_kluemper

→ View representative tweet

CheckMate 214 final 9-year follow-up: durable survival with nivolumab plus ipilimumab in advanced RCC

The 9.3-year follow-up of CheckMate 214 confirms durable survival benefits of first-line nivolumab plus ipilimumab versus sunitinib in advanced renal cell carcinoma. RCC-specific survival (HR 0.68) closely paralleled overall survival (HR 0.69), and a favorable-risk OS trend also favors nivolumab plus ipilimumab (HR 0.80) with higher rates of complete response and durable responses. After nearly a decade of data, specialists are debating whether this sustained OS benefit cements nivolumab plus ipilimumab as the enduring first-line standard for intermediate and poor-risk advanced RCC.

Discussed by: @OncoAlert, @OncoAlert

→ View representative tweet

EU approval of tumor-agnostic trastuzumab deruxtecan raises HER2 testing questions in urothelial cancer

The EU has approved Enhertu as the first tumor-agnostic HER2-directed ADC for previously treated patients with HER2 IHC3+ metastatic solid tumors with no satisfactory treatment options. A critical practical issue raised by oncologists is that this approval is based on HER2 IHC 3+ status, which is not captured by NGS — making proactive HER2 IHC testing essential for patients potentially eligible for T-DXd, including those with metastatic urothelial carcinoma. The operative question is which scoring system and tissue source should guide testing in urothelial cancer given this limitation of NGS.

Discussed by: @EladSharonMD, @OncoAlert, @OncoAlert

→ View representative tweet

ARTO long-term OS analysis: SBRT metastasis-directed therapy extends survival in oligometastatic CRPC

The long-term unplanned OS analysis of ARTO reported a median overall survival of 50 months (95% CI 36–NR) in the control group versus not reached (95% CI 55–NR) in the experimental group receiving SBRT added to abiraterone plus ADT (HR 0.55, 95% CI 0.33–0.92, p=0.021). Clinicians described this as an overall survival advantage demonstrated for the first time for radiotherapy in advanced metastatic prostate cancer. The open debate is whether this phase 2 signal justifies routine SBRT to all metastatic sites in oligometastatic CRPC or whether phase 3 confirmation is required before broad adoption.

Discussed by: @OncoAlert, @MedwatchKate

→ View representative tweet

Update: PROTEUS perioperative apalutamide draws practice-changing debate in EUO letters and editorials

Published editorials and letters in response to the PROTEUS trial are split on whether perioperative apalutamide should be adopted broadly. One editorial, by Giuseppe Di Lorenzo and Francesco Montorsi, frames PROTEUS as a practice-changing trial and asks whether clinicians are ready to embrace perioperative apalutamide for all high-risk patients. A second editorial, by Isabel Heidegger and Pierre Blanchard et al., positions the trial as potentially premature escalation, with the central question being whether broad adoption for all high-risk localized prostate cancer is justified at this stage.

Discussed by: @OncoAlert, @OncoAlert

→ View representative tweet

🔥 Top Ranked Tweets

OncoAlert @OncoAlert

RT @OncoAlert: Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: final analysis of efficacy and safety from the phase III CheckMate 214 trial

https://t.co/0lJSQi3EYq

The 9.3-year follow-up of CheckMate 214 ✅️ confirms durable survival benefits of first-line nivolumab plus ipilimumab versus sunitinib in advanced renal cell carcinoma. NIVO+IPI 🧪 maintained superior overall survival, progression-free survival, and long-lasting responses, especially in intermediate/poor-risk patients. Long-term grade 3–4 treatment-related adverse events were lower than with sunitinib.

These findings reinforce NIVO+IPI as an enduring first-line standard of care for aRCC. #KidneyCancer

@DrChoueiri
@AlbigesL
@Dr_SabyGeorge
@cdanicas
@brian_rini
@motzermd
@HHammersMD
@ERPlimackMD
@tompowles1
@ViktorGruenwald

Ping OncoAlert Faculty
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