Oncology

AI-assisted subtyping improves response after CDK4/6 resistance in HR+/HER2- metastatic breast cancer

The LINUX phase II platform trial randomized 105 HR+/HER2- metastatic breast cancer patients post-CDK4/6 to AI-based subtype-guided therapy or physician’s choice. Objective response rates were higher with subtyping in all four SNF groups: 10% versus 0%, 65% versus 30%, 40% versus 30%, and 70% versus 20%. Grade 3-4 treatment-related adverse events occurred in 37% of patients in both arms, indicating no excess toxicity from AI-guided selection. Benefits were most pronounced in SNF2 and SNF4, supporting further phase III evaluation of AI-assisted precision post-CDK4/6 strategies. 1

Durvalumab consolidation shows greater survival benefit when started from week 5 after chemoradiation

This nationwide electronic health record analysis included 854 stage III NSCLC patients treated with concurrent chemoradiation from 2019-2023. Durvalumab use overall improved survival versus no durvalumab, with an adjusted hazard ratio for death of 0.44. When timing was analyzed, initiation within 4 weeks showed no statistically significant survival advantage, with an adjusted hazard ratio of 0.81. Survival benefit became significant from week 5 and did not deteriorate when durvalumab was started after week 6. 2

Tumor-informed WGS ctDNA stratifies rectal cancer patients for organ preservation and relapse risk

This study applied a primary-tumor-informed whole-genome ctDNA assay to estimate tumor fraction in locally advanced rectal cancer. Baseline tumor fraction significantly predicted sustained clinical complete response after neoadjuvant therapy. High tumor fraction during or after neoadjuvant therapy was associated with lower sustained response and higher relapse risk, arguing against watch-and-wait in such cases. Very low tumor fraction during surveillance was frequent among non-recurrent patients, suggesting residual low-level ctDNA may not mandate intervention. 3