Martín Lázaro

#ASCO26 GU Oncology Spotlight 🚨 🔬 Abstract 4521 | CaboNivo in non–clear cell RCC Final results of phase 2 cabozantinib + nivolumab in patients with non–clear cell renal cell carcinoma Presented by Darren R. Feldman, MD @ASCO @OncoAlert Important final dataset in a difficult RCC space. Non–clear cell RCC represents a biologically diverse group of kidney cancers, often with fewer prospective data and historically poorer outcomes than clear cell RCC. 🔵 Study design Investigator-initiated phase 2 study: ➡️ cabozantinib 40 mg daily ➡️ nivolumab 240 mg q2w or 480 mg q4w Cohort 1 included: • papillary RCC • FH-deficient RCC • unclassified RCC • translocation-associated RCC Chromophobe RCC was evaluated separately and closed early for inefficacy. 🟢 Final efficacy signal With longer follow-up of ~50 months, CaboNivo reaffirmed antitumor activity in non–clear cell RCC. In cohort 1: • N = 53 • PR/CR: 43% • median PFS: 11 months • median OS: 28 months Responses were seen across several non–clear cell histologies, with a particularly notable signal in FH-deficient RCC: ➡️ 7/8 patients had an objective response. 🔵 Why it matters Non–clear cell RCC is not one disease. Histology matters. Biology matters. And prospective treatment data remain limited. This final analysis supports cabozantinib + nivolumab as an active regimen for selected patients with non–clear cell RCC histologies, especially papillary, FH-deficient, unclassified, and translocation-associated disease. 🟠 Safety Toxicity was consistent with known cabozantinib + nivolumab profiles. Grade 3/4 treatment-emergent AEs occurred in a substantial proportion of patients, and discontinuations due to AEs occurred with cabozantinib, nivolumab, or both. So this is active therapy — but not low-burden therapy. 🧠 My take CaboNivo is one of the more clinically useful prospective datasets in non–clear cell RCC. The key message is not “treat all non–clear cell RCC the same.” It is: ➡️ use histology ➡️ recognize biologic subgroups ➡️ avoid assuming clear-cell algorithms fully apply ➡️ consider CaboNivo as a treatment option where prospective evidence supports activity ➡️ continue building trials specific to rare RCC subtypes For non–clear cell RCC, better classification is the beginning of better treatment. #ASCO26 #GUOnc #KidneyCancer #RCC #NonClearCellRCC #PapillaryRCC #FHdeficientRCC #Cabozantinib #Nivolumab #PrecisionOncology @OncLive @TargetedOnc @CancerNetwrk @ASCOPost @ecancer @VJOncology @curetoday @JCO_ASCO

#ASCO26 GU Oncology Spotlight 🚨 🔬 Abstract 5017 | PROTRACT ctDNA-guided biomarker-directed therapy vs physician/patient choice in mCRPC progressing after abiraterone/prednisone Presented by Corinne Maurice-Dror, MD @ASCO @OncoAlert This is a very relevant precision-oncology question in prostate cancer: ➡️ Can ctDNA help guide whether a patient should receive docetaxel or enzalutamide after progression on abiraterone? PROTRACT tested a simple treatment-selection strategy: 🔵 Biomarker-directed arm • ctDNA ≥2% → docetaxel • ctDNA <2% → enzalutamide vs 🟠 Physician/patient choice • docetaxel or enzalutamide, based on clinical preference Primary endpoint: PFS Secondary endpoints included OS, PSA50 response, PFS2, safety, and ctDNA correlatives. 🔵 Why this matters This trial directly addresses a common real-world problem: After abiraterone progression in mCRPC, treatment choice is often based on clinical judgment, patient preference, fitness, access, and toxicity concerns. But biology may matter. A higher ctDNA fraction may reflect more aggressive disease biology and could potentially support moving toward chemotherapy rather than sequential AR pathway inhibition. 🔵 Feasibility signal The study randomized 42 patients before early termination due to slow accrual. Importantly: ➡️ 57% of patients had discordance between physician/patient preference and ctDNA-directed assignment. That is the key signal. ctDNA guidance would have changed the treatment direction for more than half of patients. 🟠 Important caveat This was underpowered and stopped early. So PROTRACT should not be read as a definitive efficacy trial. But it is still highly informative because it shows how often biomarker-directed treatment selection may differ from usual clinical choice. 🔵 My take PROTRACT is important not because it settles the sequencing question, but because it frames the next one: ➡️ Can ctDNA move from prognostic biomarker to treatment-selection tool in mCRPC? The future algorithm may not simply ask: “ARPI again or chemotherapy?” It may ask: What does the tumor biology suggest this patient needs next? #ASCO26 #GUOnc #ProstateCancer #mCRPC #ctDNA #PrecisionOncology #Biomarkers #ClinicalTrials #TreatmentSequencing @OncLive @TargetedOnc @CancerNetwork @ASCOPost @ecancer @VJOncology @curetoday

#ASCO26 GU highlight 🚨 LBA1 PROTEUS Perioperative apalutamide + ADT in high-risk localized / locally advanced prostate cancer @ASCO @OncoAlert @NEJM Presented by @MaryEllenTaplin Published in @NEJM bit.ly/43lrZR3 This is a major perioperative prostate cancer dataset. #PROTEUS tested 6 cycles of neoadjuvant + 6 cycles of adjuvant apalutamide added to ADT around radical prostatectomy. Key results: • pCR / minimal residual disease: 8.9% vs 1.0% • 5-year metastasis-free survival: 78.2% vs 73.5% • HR for distant metastasis or death: 0.80 • Event-free survival: 57.1 vs 38.4 months • Time to first subsequent therapy: 74.2 vs 41.5 months Why it matters: For years, systemic perioperative intensification around prostatectomy has been difficult to establish in high-risk localized prostate cancer. PROTEUS gives phase 3 evidence that deeper androgen-receptor pathway inhibition can improve pathologic response and delay clinically relevant recurrence events. Important caveats: This was not surgery alone vs systemic therapy. The control arm received perioperative ADT + placebo. MFS by conventional imaging alone was not significantly different. Grade 3/4 AEs were higher with apalutamide, largely driven by rash. My take: This is practice-informing and potentially paradigm-shaping, but implementation will require careful patient selection, toxicity counseling, imaging context, and multidisciplinary discussion. @EAntonarakis @DanaFarber_GU @DrChoueiri @montypal @tompowles1 @brian_rini @PGrivasMDPhD @DrRanaMcKay @AliciaMorgans @amerseburger @NealShoreMD @DrYukselUrun @BraunMDPhD @DrSpratticus @EAntonarakis @KOSJ12 @LoebStacy @apolo_andrea @AndreaNecchi @DrDanielHeng @neerajaiims @OncLive @TargetedOnc @CancerNetwrk @ASCOPost @VJOncology @ecancer #ProstateCancer #GUonc #Oncology