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Disease-free survival (DFS) and time to recurrence (TTR) with circulating tumor (ct) DNA–based decision for adjuvant treatment in colon cancer stage II (CIRCULATE): An AIO (KRK-0217)/ABCSG trial.

This is the first prospective randomized trial demonstrating that ctDNA guided Adjuvant chemotherapy (ACT) improves time to recurrence (TTR) and Disease-free survival (DFS) in stage II colon cancer pts without clinical risk factors, pt with negative CtDNA had better overall survival (OS) and DFS than pts with positive CtDNA, Pts who with Positive CtDNA who and chemotherapy also had better DFS compared to the ones who underwent surveillance (77% vs 38%).

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Role of neoadjuvant versus adjuvant chemotherapy, dose density, and treatment schedule in biologically high-risk HR+/HER2- breast cancer: A pooled analysis of the WSG ADAPT-HR+/HER2- and PlanB trials.

1467 pts with RS > 25 and 551 with clinically (neoadjuvant cohort in ADAPT-HR+/HER2-) or pathologically N2, (longer) docetaxel-based CTx showed better distant, invasive disease-free survival in N2-3 pts patients with RS ≤25, OS was also shown in pts with RS>25 anthracycline regimens did not show a significant survival difference in high-risk HR+/HER2 whether used in neoadjuvant or adjuvant setting. So may be no anthracycline for HR+ve pts who are high risk disease.

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Radiographic Progression With and Without Prostate-Specific Antigen Rise in Patients With Advanced Prostate Cancer Treated With Enzalutamide

An important post-hoc analysis from ARCHES and PROSPER that quantifies something we've suspected clinically, roughly 1 in 4 enzalutamide-treated patients who progress radiographically have no prostate-specific antigen (PSA) rise, and the majority won't meet PCWG2/3 PSA progression criteria. Liver metastases were 5-fold more common at radiographic progression on enzalutamide versus control, suggesting lineage plasticity and AR-independent clones are the culprit. Bottom line for practice: don't wait for PSA to rise before imaging your metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC) patients on ARPIs, periodic cross-sectional imaging, especially in the first two years, is warranted regardless of PSA trend.

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Phase I Study of Mosperafenib, a Novel Paradox Breaker B-Raf Proto-Oncogene Serine/Threonine Kinase (BRAF) Inhibitor, in Patients With BRAF V600–Mutant Solid Tumors

Intriguing phase I signal for this next-generation paradox-breaker BRAF inhibitor with brain-penetrant properties. The 24% overall response rate (ORR) as a single agent is striking given that 60% of patients had prior BRAFi exposure, and seeing responses in that pretreated group is the most exciting finding. In BRAF-naïve colorectal cancer (CRC) specifically, a 24% ORR and 7.3-month progression-free survival (PFS) as monotherapy compares favorably to encorafenib/cetuximab in BEACON, which is a bold cross-trial comparison but hard to ignore. Safety looks cleaner than approved BRAFis, with no keratoacanthoma or palmar-plantar erythrodysesthesia, and a lower discontinuation rate. Brain penetrance showed early hints of intracranial benefit worth exploring further. One to watch closely as it moves into combinations.

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The Pathologic Response Evaluation and Detection in Circulating Tumor-DNA Study: Ultrasensitive Circulating Tumor-DNA Assessment of Breast Cancer Minimal Residual Disease

Primary objective not met, ctDNA clearance post- neoadjuvant therapy (NAT) cannot reliably predict pathologic complete response (pCR) and shouldn't be used to defer surgery. But the prognostic data are striking: post-NAT ctDNA positivity independently predicted recurrence in triple-negative breast cancer (TNBC) (HR 8.9), and the postsurgical landmark analysis is essentially binary, 100% of ctDNA-positive patients recurred while 94% of ctDNA-negative patients were disease-free at 5 years (HR 128). Not practice-changing yet pending prospective utility trials, but this strongly validates ultrasensitive ctDNA as a prognostic tool and a smart enrollment biomarker for future escalation/de-escalation trials.

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