📬 GU Oncology Intelligence Digest — Week 2026-W36

KEYNOTE-564 five-year results show adjuvant pembrolizumab maintains a survival benefit in ccRCC, GETUG-AFU 18 reports 10-year outcomes with dose-escalated radiotherapy, and panitumumab-based EGFR blockade shows prospective activity in SMARCB1-deficient renal medullary carcinoma.

⚡ TL;DR

📄 Publications

Adjuvant pembrolizumab for the treatment of clear cell renal cell carcinoma: Five-year results from the phase III KEYNOTE-564 study. — 994 participants randomized to pembrolizumab (n = 496) or placebo (n = 498), with median time from randomization to data cutoff of 70 months

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Renal medullary carcinoma research program broadens from molecular profiling and imaging to a Trop-2 ADC trial — The largest renal medullary carcinoma molecular profiling effort was paired with translational testing designed to uncover targetable vulnerabilities
GETUG-AFU 18 ten-year results support dose escalation to 80 Gy with long-term ADT, but the survival signal draws caveats — Phase III with N=505 high-risk non-metastatic prostate cancer; at 9.5-year median follow-up 10-year PFS was 83.6% vs 72.2% (HR 0.56, p<0.0001), 10-year OS 77.0% vs 65.9% (HR 0.61, p=0.004) and 10-year prostate cancer-specific survival 95.6% vs 90.0% (HR 0.48, p=0.009)
Panitumumab-based EGFR blockade in SMARCB1-deficient renal medullary carcinoma reports a 53.9% objective response rate — Panitumumab outperformed erlotinib in preclinical models and showed clinical activity across 26 patients treated at 10 centers, with a 53.9% objective response rate and 15.4% complete response rate
Meta-analysis of perioperative MIBC trials places enfortumab vedotin plus pembrolizumab ahead of gemcitabine-cisplatin without declaring a survival winner — A meta-analysis of three phase III trials in cisplatin-eligible muscle-invasive bladder cancer found intensified or immune-based neoadjuvant regimens outperform gemcitabine-cisplatin, with EVP producing the strongest improvements in event-free survival, overall survival and pathologic complete response

Full details below ↓

📄 What's Being Published

Manuscripts:

Adjuvant pembrolizumab for the treatment of clear cell renal cell carcinoma: Five-year results from the phase III KEYNOTE-564 study. — Haas N B et al., Ann Oncol

994 participants were randomized to pembrolizumab (n = 496) or placebo (n = 498), with a median time from randomization to data cutoff of 70 months. Pembrolizumab improved disease-free survival versus placebo (HR 0.71, 95% CI 0.59–0.86), with estimated 5-year DFS rates of 60.9% versus 52.2%; overall survival was also improved (HR 0.66, 95% CI 0.48–0.90), with estimated 5-year OS rates of 87.7% versus 82.3%.

Clinical bottom line: With 70 months of median follow-up, the disease-free survival advantage of one year of adjuvant pembrolizumab in high-risk clear cell RCC has matured into a sustained overall survival benefit, confirming it as the adjuvant standard.

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APUC-6 Genes as a Potential Prognostic and Predictive Biomarker in the CHAARTED Prostate Cancer Trial. — Shi Xiaolei et al., JCO Precis Oncol

Transcriptomic data from 160 patients in the phase III E3805 CHAARTED trial were analyzed and stratified by APUC-6 and AR expression. Patients with APUC-6-high/AR-low expression showed significantly improved OS (HR 0.31; 95% CI 0.16 to 0.61; P = .0003) but did not appear to benefit from the addition of docetaxel, while statistical interaction analysis supported that APUC-6-low/AR-low patients were more likely to benefit from docetaxel (HR 0.36; 95% CI 0.19 to 0.66; P = .001).

Clinical bottom line: The APUC-6/AR expression panel remains the sharpest available transcriptomic tool for deciding which metastatic castration-sensitive patients actually gain from adding docetaxel to androgen deprivation.

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Expression patterns of potential targets for antibody-directed therapy in metastatic castration-resistant prostate cancer patients. — van Dijk Tanja C et al., Eur J Cancer

Gene expression of 62 antibody-targetable proteins was analyzed in 296 mCRPC biopsies. Target expression did not correlate with genomic classifications — including homologous recombination deficiency, microsatellite instability, CDK12, TP53, PTEN, or AR alterations — but did associate with transcriptomic subtypes. Notably, CD46 was highly expressed in tumors with low KLK2, FOLH1, and STEAP1 expression, a subgroup associated with poor prognosis.

Clinical bottom line: Antibody target selection in mCRPC should be driven by transcriptomic subtype rather than genomic alterations, and CD46 is the target that covers the subgroups current PSMA- and STEAP1-directed agents miss.

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Darolutamide-based triplet therapy versus androgen receptor pathway inhibitor-based doublet therapy for metastatic castration-sensitive prostate cancer: a real-world analysis using the TriNetX database. — Tohi Yoichiro et al., Jpn J Clin Oncol

1841 patients met eligibility criteria; after 1:1 propensity score matching (n = 329), triplet therapy was associated with a statistically significant improvement in overall survival compared with doublet therapy (HR 0.601; 95% CI 0.420–0.862; log-rank P = .005). PSA ≤0.2 ng/ml was achieved by 26.4% versus 17.0% at 3 months and 50.5% versus 40.1% at any time in the triplet versus doublet groups, respectively.

Clinical bottom line: In real-world practice a darolutamide-docetaxel triplet outperformed ARPI doublets on both survival and depth of PSA response, supporting triplet intensification for docetaxel-fit metastatic castration-sensitive patients.

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🗂 Every paper considered this week, including the ones that didn’t make it →

🗣️ 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).

Renal medullary carcinoma research program broadens from molecular profiling and imaging to a Trop-2 ADC trial

The largest molecular profiling effort in renal medullary carcinoma, paired with translational testing designed to uncover targetable vulnerabilities, was published in Cell Reports Medicine; a companion paper in the Journal of Nuclear Medicine examined whether FDG PET/CT may change how renal medullary carcinoma is staged and help patients get the right treatment faster. A prospective trial of ixazomib plus gemcitabine and doxorubicin was tested in 30 patients with SMARCB1-deficient renal medullary carcinoma, and the STaRMC trial — testing sacituzumab tirumotecan, a Trop-2 ADC, in SMARCB1-deficient renal medullary carcinoma — is now enrolling at MD Anderson. With EGFR blockade, proteasome inhibition, and now a Trop-2 ADC all in play, the debate among oncologists centers on how systemic therapy should be sequenced in this disease.

Discussed by: @PavlosMsaouel, @PavlosMsaouel, @PavlosMsaouel, @PavlosMsaouel, @JadChahoud, @PavlosMsaouel

→ View representative tweet

GETUG-AFU 18 ten-year results support dose escalation to 80 Gy with long-term ADT, but the survival signal draws caveats

In this phase III trial of 505 men with high-risk non-metastatic prostate cancer, long-term ADT plus 80 Gy versus 70 Gy EBRT was assessed at a 9.5-year median follow-up: 10-year PFS was 83.6% versus 72.2% (HR 0.56, p<0.0001), 10-year OS 77.0% versus 65.9% (HR 0.61, p=0.004), and 10-year prostate cancer-specific survival 95.6% versus 90.0% (HR 0.48, p=0.009), with similar rates of severe toxicity between groups. A critical caveat circulated widely: only 92 progression events occurred versus 197 planned, and the 10-year PFS analysis was post hoc, meaning OS and cancer-specific survival require cautious interpretation. One radiation oncologist read the data as confirming that higher RT dose reduces recurrence while the OS benefit was driven by non-prostate-cancer events, and clinicians drew a direct contrast between GETUG-AFU 18 supporting local intensification in N0 disease and STAMPEDE supporting systemic intensification in a higher-risk population — a distinction that sharpens the question of how much weight these survival curves should carry in the PSMA-PET era.

Discussed by: @OncoAlert, @OncoAlert, @OncoAlert, @neerajaiims, @TheLancetOncol

→ View representative tweet

Panitumumab-based EGFR blockade in SMARCB1-deficient renal medullary carcinoma reports a 53.9% objective response rate

Published in Clinical Cancer Research, a study of panitumumab-based EGFR blockade in renal medullary carcinoma showed that panitumumab outperformed erlotinib in preclinical models and demonstrated clinical activity across 26 patients treated at 10 centers, achieving a 53.9% objective response rate and a 15.4% complete response rate. Oncologists described the findings as prospective clinical activity in a rare, aggressive kidney cancer typically refractory to standard RCC therapies, which sharpens debate over whether wild-type EGFR blockade with panitumumab should now be the default systemic option for SMARCB1-deficient renal medullary carcinoma outside a trial.

Discussed by: @PavlosMsaouel, @OncoAlert, @OncoAlert

→ View representative tweet

Meta-analysis of perioperative MIBC trials places enfortumab vedotin plus pembrolizumab ahead of gemcitabine-cisplatin without declaring a survival winner

A meta-analysis of three phase III trials — VESPER, NIAGARA, and KEYNOTE-B15/EV-304 — in cisplatin-eligible muscle-invasive bladder cancer found that intensified or immune-based neoadjuvant regimens outperform gemcitabine-cisplatin; enfortumab vedotin plus pembrolizumab produced the strongest improvements in event-free survival, overall survival, and pathologic complete response, while gemcitabine-cisplatin plus durvalumab and ddMVAC also improved outcomes. Clinicians acknowledged that EV plus pembrolizumab shows the strongest numerical EFS/OS signal and pCR effect versus GC, but cautioned that indirect comparisons are hypothesis-generating, with no survival winner yet declared — leaving open the question of whether head-to-head evidence is still required before naming a preferred perioperative regimen.

Discussed by: @urotoday, @OncoAlert, @OncoAlert, @ChandrakanthMv

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🔥 Top Ranked Tweets

OncoAlert @OncoAlert

RT @APCCC_Lugano: Eight years later 📅 , the question is no longer whether enzalutamide works in mHSPC—it’s how much long-term survival benefit we should expect from early disease control.

Article 📰
https://t.co/jZhp3G6zOm

Eight-year outcomes of testosterone suppression plus enzalutamide or a non-steroidal anti-androgen for metastatic, hormone-sensitive prostate cancer (ENZAMET; ANZUP 1304)

With 8.1 years of follow-up in mHSPC, enzalutamide 💊 plus testosterone suppression continued to improve survival versus first-generation NSAA therapy. Eight-year OS was 50% 🆚 40%, with fewer prostate cancer deaths and markedly better clinical PFS (43% vs 20%). One-third of patients remained on enzalutamide at 8 years, mostly at full dose. PSA ≤0.2 ng/mL at 7 months identified patients with particularly favorable long-term outcomes, supporting durable disease control. #ProstateCancer

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@OncoAlert 🚨 #LPCCC27
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