Oncology

Only high-tier, prospectively supported genomic matches improve survival in advanced solid tumors

In this nationwide Australian precision oncology cohort, 3383 adults with advanced refractory solid tumors underwent comprehensive genomic profiling. Clinically active biomarkers with prospective evidence (tiers 1–3A) were present in 37.5% of patients. Among treated patients with tier 1–3A biomarkers, matched therapy improved median overall survival vs unmatched therapy (21.2 vs 12.8 months; adjusted HR 0.60). Therapies matched only to investigational or repurposed evidence (tiers 3B/4) did not improve survival compared with unmatched therapy (adjusted HR 1.04). 1

ctDNA FGFR testing complements tissue for erdafitinib selection in metastatic urothelial cancer

This prospective multicenter study profiled plasma ctDNA in 208 patients with metastatic urothelial carcinoma undergoing clinical FGFR tissue testing for erdafitinib eligibility. Across evaluable baseline samples, FGFR alterations were present in 26% by either tissue or ctDNA. In 125 patients with paired baseline ctDNA and tissue, FGFR status was 90% concordant, and ctDNA had 84% sensitivity for tissue-detected alterations while adding seven extra actionable cases. Serial plasma collections after baseline clarified FGFR status over time, supporting real-time monitoring of alterations. 2

Neoadjuvant CAPOX does not improve DFS versus upfront surgery in locally advanced colon cancer

The NeoCol phase III trial randomized 248 patients with CT-staged locally advanced colon cancer to upfront surgery or three cycles of neoadjuvant CAPOX followed by surgery. Three-year disease-free survival was similar with upfront surgery and neoadjuvant chemotherapy (87% vs 83%; P = .36), indicating no DFS benefit. Neoadjuvant CAPOX was feasible, downstaged tumors, and reduced the proportion meeting criteria for adjuvant chemotherapy (73% vs 59%). Postoperative complications, adverse events, and quality of life were comparable between arms, suggesting no major safety penalty. 3

Hypoxia-responsive CEA CAR T cells show manageable toxicity and early activity in solid tumors

This phase 1 dose-escalation and expansion study evaluated PC13, a hypoxia-responsive CEA-targeted CAR T-cell therapy, in 43 heavily pretreated CEA-positive solid tumor patients. Participants received PC13 intraperitoneally (n = 17) or intravenously (n = 26) based on dominant metastatic site. Toxicity was manageable, with grade 3 diarrhea in 20.9% and predominantly grade 1–2 cytokine release syndrome in 76.7% of patients. Disease control rates were 82.4% for intraperitoneal and 68.0% for intravenous delivery, with objective response rates of 23.5% and 8.0%, respectively. 4