Oncology

Postoperative ctDNA identifies stage III colon cancer patients deriving benefit from adjuvant celecoxib

In this post hoc analysis of CALGB/Alliance/SWOG 80702, 940 stage III colon cancer patients had postoperative ctDNA assessed before adjuvant therapy. ctDNA positivity (18.4% of patients) was strongly prognostic for worse DFS and OS versus ctDNA negativity, with adjusted HRs around 6. In ctDNA-positive patients, adding celecoxib to adjuvant chemotherapy improved DFS (aHR 0.61) and OS (aHR 0.62) versus placebo. In ctDNA-negative patients, celecoxib did not materially improve survival, and treatment-by-ctDNA interaction tests were not statistically significant. These data support ctDNA as a powerful prognostic marker and a candidate predictive biomarker to individualize adjuvant COX-2 inhibition intensity. 1

Five-year NATALEE data show durable adjuvant benefit of ribociclib plus NSAI in HR+/HER2− early breast cancer

NATALEE randomized stage IIA–III HR+/HER2− early breast cancer patients to ribociclib plus NSAI versus NSAI alone, with goserelin for premenopausal patients and men. At 55.4 months median follow-up, ribociclib plus NSAI maintained an invasive DFS benefit, HR 0.716 with a growing 5-year absolute difference of 4.5%. Benefit was consistent across key subgroups, including node-negative patients, and across several distant recurrence–focused endpoints. Overall survival showed a numerically favorable trend for ribociclib, HR 0.800, with a nominally significant one-sided P value but immature data. These results support 3 years of adjuvant ribociclib plus endocrine therapy as a risk-reducing option across a broad HR+/HER2− early breast cancer population. 2

Adding checkpoint blockade to perioperative chemotherapy improves outcomes in resectable gastric and GEJ cancer

This meta-analysis pooled four phase 2/3 trials (n=2358) testing ICIs plus perioperative chemotherapy versus chemotherapy alone in resectable gastric or GEJ cancer. Chemo-immunotherapy significantly increased pathologic complete response, RR 2.80, without improving R0 resection rates. Event-free survival and overall survival improved with ICIs, with HRs 0.76 and 0.78, respectively. Overall grade 3–5 treatment-related adverse event rates were similar, but grade 3–5 immune-related events nearly tripled and serious events modestly increased. The authors conclude perioperative chemo-immunotherapy is efficacious with manageable toxicity, but emphasize the need for specialized centers and longer follow-up. 3