Oncology

SONIA: No overall survival gain with first-line CDK4/6i in HR+/HER2– advanced breast cancer

In SONIA, 1050 untreated HR+/HER2– advanced breast cancer patients were randomized to CDK4/6 inhibitor plus aromatase inhibitor first line versus second line with fulvestrant. At 58.5 months’ median follow-up, median overall survival was similar: 47.9 months first line versus 48.1 months second line (HR 0.91; 95% CI, 0.77-1.07; P=.24). Post hoc analyses suggested an overall survival benefit from first-line CDK4/6i in premenopausal, but not postmenopausal, patients (interaction P=.01). First-line use produced more grade ≥3 toxicity and greater treatment burden, while subsequent therapy patterns were similar between arms. 1

Second-line CD19 CAR-T beats chemo±ASCT in early relapsed LBCL

This meta-analysis pooled three randomized trials and one real-world study, totaling 1199 adults with early relapsed or refractory large B-cell lymphoma. Second-line CD19 CAR-T significantly improved overall survival versus standard chemo±autologous transplant (HR 0.75; 95% CI, 0.62-0.92). Event-free and progression-free survival benefits were larger (EFS HR 0.51; 95% CI, 0.33-0.78; PFS HR 0.47; 95% CI, 0.39-0.58). Three-year OS and PFS estimates favored CAR-T over standard care, with consistent efficacy across age, histology, and relapse subgroups. 2

Perioperative ctDNA strongly predicts outcomes after resection of pancreatic cancer

This meta-analysis of 18 studies including 965 surgically treated PDAC patients evaluated pre- and postoperative ctDNA as prognostic markers. Preoperative ctDNA positivity was associated with worse disease-free survival (HR 2.08; 95% CI, 1.63-2.65) and overall survival (HR 2.31; 95% CI, 1.66-3.22). Postoperative ctDNA positivity conferred even higher risk, with DFS HR 3.29 and OS HR 3.42. The adverse prognostic impact persisted in both upfront resection and neoadjuvant-treated subgroups. 3

KEYNOTE-775: Five-year data confirm durable benefit of lenvatinib+pembrolizumab in advanced endometrial cancer

In KEYNOTE-775, 827 previously treated advanced endometrial cancer patients were randomized to lenvatinib plus pembrolizumab versus doxorubicin or paclitaxel. At 68.8 months’ median follow-up, five-year overall survival in all-comers was 19.9% with lenvatinib+pembrolizumab versus 7.7% with chemotherapy. Five-year OS benefit was marked in mismatch repair–deficient disease (36.5% vs 9.8%) and remained in mismatch repair–proficient tumors (16.7% vs 7.3%). Five-year progression-free survival rates also favored the combination across subgroups, despite more subsequent systemic therapy and crossover in the control arm. 4