Neeraj Agarwal, MD, FASCO

JUST In: TALAPRO-3 published in @NEJM Adding #talazoparib to enzalutamide/ADT =>3-year rPFS: 77% vs 56% in HRR-deficient metastatic prostate cancer ! Looking forward to full presentation by @neerajaiims who keeps changing SOC, one trial at a time. @ASCO #ASCO26 @OncoAlert https://t.co/nXiPk4DIXg

Cheers to @neerajaiims on his presentation of the #TALAPRO3 data w simultaneous @NEJM publication! It reflects the dream of many clinical investigators in #oncology - to lead a trial & generate paradigm shifting data in a field that you have devoted your life to (in this case, #prostatecancer). If you see him at #ASCO26, inquire about his remarkable story. At @huntsmancancer, he built the GU program from scratch into one of the highest performing programs worldwide. He did this over the span of nearly two decades through mentorship of his faculty & fellows (@umangtalking @maughanonc @ziremozay @ggebraelmd et al), extensive outreach to the local community & active participation & leadership in multiple studies (a mix of industry, ISTs & @SWOG). Simply amazing.

#ASCO26 GU Oncology Spotlight 🚨 🔬 LBA5007 | TALAPRO-3 Talazoparib + enzalutamide vs placebo + enzalutamide in HRR-altered mCSPC Presented by Neeraj Agarwal, MD, FASCO @neerajaiims @OncoAlert @ASCO TALAPRO-3 addresses a key question in metastatic castration-sensitive prostate cancer: ➡️ Can PARP inhibition improve outcomes when added upfront to AR pathway inhibition in patients with HRR gene alterations? The answer: yes, with a clinically meaningful rPFS benefit. 🟦 Primary endpoint: investigator-assessed rPFS Talazoparib + enzalutamide reduced the risk of radiographic progression or death by 52% vs placebo + enzalutamide. 📊 Key result: • HR: 0.48 • 95% CI: 0.36–0.65 • p < 0.0001 • median rPFS: NR vs 45.8 months • 36-month rPFS: 76.6% vs 56.2% That is a strong signal for upfront intensification in a molecularly selected mCSPC population. 🧬 Benefit by HRR subgroup The rPFS benefit was seen in both BRCA and non-BRCA HRR-altered subgroups. BRCA1/2m subgroup • HR: 0.37 • 36-month rPFS: 77.2% vs 48.8% • median rPFS: NR vs 35.1 months Non-BRCA1/2m subgroup • HR: 0.57 • 36-month rPFS: 76.2% vs 60.2% This is important because the magnitude of PARP benefit has historically been strongest in BRCA-altered disease, while non-BRCA HRR alterations have been more heterogeneous. 🟩 Tumor response Among patients with measurable disease: • ORR: 74.7% with tala + enza • ORR: 67.0% with placebo + enza • duration of response was prolonged with the combination So the main story is not simply response rate — it is durability and disease control. 🟥 Safety: anemia is the key toxicity The major toxicity signal was hematologic, especially anemia. In the talazoparib arm: • median time to grade 3–4 anemia: 3.2 months • 40% received packed RBC transfusion • 14% had recurrent grade 3–4 anemia after dose reduction • 5% discontinued talazoparib due to anemia Most treatment-emergent AEs were manageable with dose modification and supportive care, but this toxicity matters in long-duration mCSPC treatment. 🟨 Patient-reported outcomes Importantly, addition of talazoparib to enzalutamide generally did not result in clinically meaningful differences in PROs vs enzalutamide alone, except appetite loss by EORTC QLQ-C30. This helps contextualize tolerability beyond AE tables. 💬 My take TALAPRO-3 strengthens the case for early molecular testing in prostate cancer. For patients with HRR-altered mCSPC, talazoparib + enzalutamide offers a meaningful rPFS advantage. But implementation will require thoughtful patient selection and toxicity management. Key clinical questions: 🔹 Which HRR alterations derive the greatest absolute benefit? 🔹 How should we weigh benefit in non-BRCA HRR alterations? 🔹 How do we manage anemia during long-term therapy? 🔹 When should testing be done — and in whom? Bottom line: This is not a “PARP inhibitor for everyone” message. It is a strong reminder that molecularly selected intensification is becoming central to mCSPC care. Early HRR testing is no longer optional background information — it is increasingly treatment-shaping. #ASCO26 #GUOnc #ProstateCancer #mCSPC #PARPInhibitors #Talazoparib #Enzalutamide #PrecisionOncology #HRR #BRCA

So proud to watch the my dear friend & mentor @neerajaiims present TALAPRO-3 at #ASCO26 with a simultaneous publication in @NEJM today! Tala + enza rPFS (HR 0.48), with 3-year rPFS of 76.6% vs 56.2% in pts with HRR-deficient mHSPC. Kudos to Neeraj and entire TALAPRO-3 team on this new standard! @ASCOPost @DrChoueiri @OncoAlert @Uromigos

Thank you for highlighting @neerajaiims. 🙏Excited to share these results with the #ASCO26 community. #endRMC #kidneycancer #RenalMedullaryCarcinoma https://t.co/hHnpFL0W05

⭐️⭐️⭐️🚨🚨🚨Huge congratulations to the one & only @neerajaiims for the phenomenal first author NEJM paper simultaneously published @ASCO #ASCO26 👏🏼👏🏼👏🏼 https://t.co/pXLEy9lslD

Breaking news #ASCO26 Adding Talazoparib to enzalutamide significantly ⬆️ rPFS 👉 HR 0.48 in pts w/ mCSPC (mAPMS) #prostatecancer w/ HRRm 👉 @NEJM paper https://t.co/HmXyNvbExi 👇 @ASCO @oncoalert @urotoday @PCF_Science @OpenMedicineHQ https://t.co/86ZjBEh22O

Just happened today👏🎉👉 @FDA approved Talazoparib + enzalutamide for pts with HRRm positive mAPMS/mHSPC #prostatecancer FDA Link👉 https://t.co/VjKSoslJaV 👉 @NEJM paper https://t.co/03FcVSey5n 👇 @ASCO @oncoalert @urotoday @PCF_Science @DanaFarber_GU https://t.co/g0b6vhzSgL https://t.co/iRQ2mBPNOD

Breaking news from @ASCO #GU26 👉Adding belzutifan to adjuvant pembrolizumab significantly improves disease free survival (HR: 0.72)👉Congrats @drchoueiri & team for changing SOC again in pts with #kidneycancer @kidneycan @OncoAlert @urotoday https://t.co/7MfCXdcGqY

Ab#4519 @ASCO #ASCO26 by @RWinayak👉 https://t.co/jUT766TOBM👉Addition of CBM588 to ICB-based 1L combinations in mRCC #kidneycancer👉dysbiotic stool confers greater benefit & a potential biomarker👉Ph3 @SWOG BIOFRONT ongoing👇@montypal @nazlidizman @OncoAlert @urotoday @kidneycan https://t.co/Pl5um6ZF7H

Ab#10234 @ASCO #ASCO26 by @umangtalking👉 https://t.co/c710DwfP69👉RW data from ~136,000 pts w/ 6 most common metastatic cancers @flatironhealth👉30% of pts receive unnecessary chemo in the final month of life👇@huntsman_GU @OncoAlert @urotoday @PCF_Science @OpenMedicineHQ https://t.co/IxmOQfpnxW