The prostate cancer PSA screening story over 23 years of follow-up for >166,000 participants: more detection, small reduction of mortality NEJM nejm.org/doi/full/10.10…

After moving beyond anthracyclines, we’re now moving beyond carboplatin for HER2+ disease. We now know that: - THP x4-6 leads to pCR 50-60% of pts - adding T-DXd x4 further boosts pCR in high-risk pts - in case of RD, two ADCs can optimize outcomes Here’s my future algorithm:

Evolution of HER2 Classification The story of HER2 has moved beyond the binary of positive and negative; it’s now an evolving spectrum from low to ultralow to null—where the gray tones of biology are rewriting clinical decisions Recommended HER2 Algorithm👇

A recent study (shared below) reminded me that 𝐰𝐡𝐚𝐭 𝐦𝐚𝐤𝐞𝐬 𝐚 𝐏𝐡𝐃 𝐬𝐭𝐮𝐝𝐞𝐧𝐭 𝐡𝐚𝐩𝐩𝐲 𝐢𝐬 𝐧𝐨𝐭 𝐩𝐮𝐛𝐥𝐢𝐜𝐚𝐭𝐢𝐨𝐧𝐬 𝐨𝐫 𝐬𝐭𝐢𝐩𝐞𝐧𝐝𝐬, 𝐛𝐮𝐭 𝐠𝐨𝐨𝐝 𝐬𝐮𝐩𝐞𝐫𝐯𝐢𝐬𝐢𝐨𝐧. Over the years, I have supervised 53 PhD students, and I can say with

📊 Meta-analysis in mHSPC (>13,000 pts, 11 ph3 trials) SoC (ADT±chemo) vs SoC + ARPI ± chemo OS benefit ↓ with age HR 0.63 (<70y) vs 0.82 (≥70y) Older pts ↑CV toxicity, ↑G3–5 AEs, ↑ discontinuations In ≥70y low-vol mHSPC w/RT to the primary, ARPI adds little OS gain.

Real world outcomes with first-line osimertinib in #EGFR NSCLC Lung Cancer Journal from Tony Mok Molly Li show that for 37% of pts, progression is oligoprogressive and those pts have a longer time to treatment failure (26 vs 14m) and OS (35 vs 25m). lungcancerjournal.info/article/S0169-…

Three basic science studies this week with potential big impact for cancer treatment (and beyond) 1. Determining why BRCA2 cancers are resistant to current therapies Science Magazine science.org/doi/10.1126/sc…

A study recently published in Cancer Discover Cancer Discovery, led by Dr. Teresa Landi of the nick with the participation of multiple cancer centers such as incan mx, on lung adenocarcinoma in non-smokers, identified 3 different subtypes based on RNA sequencing data from 684 tumors.

Ten-Year Survival after Postmastectomy Chest-Wall Irradiation in Breast Cancer nejm.org/doi/full/10.10…

Hepatitis C is curable in 99% of cases with modern antivirals But, because of under-diagnosis and under-treatment, Hep C still causes >25% of liver cancers (even as projected into 2050)

Chromosome 15q15 Deletion drives brain mets in NSCLC Using 3 independent NSCLC cohorts (multi-omics study: WGS/WES, RNA seq; n=1081) 15q15 deletion was identified as a driver of brain mets in NSCLC in EGFR tumors (~60%). Loss of MGA activates MYC–OXPHOS signaling, ↑↑ BM risk

Comparative Survival in Metastatic Hormone-sensitive Prostate Cancer by Volume of Disease and Timing of Metastasis: A Living Network Meta-analysis sciencedirect.com/science/articl… This living network meta-analysis of 11 phase 3 trials shows that treatment benefits in metastatic

Now online in Cancer Discovery: Trastuzumab Deruxtecan (T-DXd) Resistance via Loss of HER2 Expression and Binding - by Wanyi Chen, Josh Drago, Sarat Chandarlapaty, and colleagues doi.org/10.1158/2159-8… Memorial Sloan Kettering Cancer Center

Triplet therapy offers the greatest survival benefit* but is still underused, mostly given to fit patients with de novo, high-volume disease due to toxicity concerns & patients’ preference to avoid chemo. In real-world practice, <40% of eligible pts receive docetaxel*, and most

Important study as suggests resistance will differ in HER2+ vs HER2-low tumors, and may account for markedly better activity in 'truly' HER2+ disease. Prediction: within 2 years, we are back to dichotomous HER2+ vs HER2-other breast cancer classification

Navigating the landscape of EGFR TKI resistance in EGFR-mutant NSCLC — mechanisms and evolving treatment approaches nature.com/articles/s4157…

ADCs and multi-specific antibodies are transforming oncology at an unprecedented pace. Of note, of 500 “enhanced mAbs” in the pipeline, > half come from China. If the current trend continues, China is expected to dominate this therapeutic sector within 5y. nature.com/articles/d4157…

Ozempic may reduce the mortality risk from colon cancer. Colon cancer patients taking GLP-1 drugs (Ozempic, Wegovy, Mounjaro) were less than half as likely to die within 5 years. This new study suggests GLP-1 drugs might specifically target obesity-driven inflammatory and

ASCENT-03 ph3 trial, Sacituzumab Govitecan in mTNBC Sacituzumab govitecan ↑ PFS 9.7 vs 6.9 mo & DoR 12.2 vs 7.2 mo vs chemotherapy becoming a 1L option for pts ineligible for immunotherapy. TROPION-Breast02 (Dato-DXd) supports the expanding role of ADCs in mTNBC