7. PEACE1: Abiraterone + ADT + docetaxel in denovo mHSPC (long-term update). - Adding abi to ADT + doce: 8-yr OS 40% vs 27% - OS HR 0.75 overall - Benefit independent of metastatic volume 8/8

6. KEYNOTE-866: PeriOp pembro + neoadj cis/gem vs placebo + chemo in cisplatin-eligible MIBC. - EFS: median 74.1 mo vs NR (HR 0.88; p=0.14) - No significant EFS or OS benefit - EV+pembro (or perhaps Durva-EV will be) preferred SOC. 7/8

5. HERIZON-GEA-01: Zanidatamab ± tislelizumab + chemo vs trastuzumab + chemo in 1L HER2+ advanced Gastric/GEJ - Zani + chemo: mOS 22.9 vs 19.6 mo (HR 0.76; p=0.0088) - Zani + TIS + chemo: mOS 27.0 vs 19.6 mo (HR 0.65); ~40% alive at 3 yrs - SoC for HER2+ in 1L 6/8

4. RASolute302: Daraxonrasib vs SOC chemo in previously treated mPDAC. - mOS: 13.2 vs 6.7 mo (HR 0.40) and @FDA ✅ for all comers. - KRAS-G12D with most activity (HR: 0.48) - Benefit across RAS G12 subgroups; FDA-approved 5/8

3. TALENT: Neoadj TDXd ± AI or → TC in HR+/HER2-low early BC. - pCR: T-DXd 7%; +AI 3%; →TC 9% - Adding ET or seq chemo did not meaningfully improve pCR. Not practice-changing. What does this mean for triple positive mBC? 👇👇 4/8

2. HORIZON-Breast06: 🇨🇳 only, Ph III Trastuzumab Rezetecan in HR+ or TNBC after 1 or fewer lines of chemotherapy for metastatic disease: - mPFS 16.6 vs. 6.8mos (chemo naive, HR: 0.25) - Benefit similar in HR+ and TNBC - Need global studies for this to be ✅ by @FDA 3/8

1. NATALEE: Adj #Ribociclib in HR+ early breast cancer (Stg IIA - III), 400mg daily (3wks on, 1wk off) for 3yrs. - 6yr OS 91.9% vs 89.7, 2.1% absolute OS - HR: 0.809 - AEs: QTc prolongation, Neutropenia. 2/8