Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer

Rákkutatás · Colorectal cancer

High‑dose vitamin D3 added to standard chemotherapy plus bevacizumab did not improve progression‑free survival in patients with metastatic colorectal cancer.

IMPORTANCE: In a phase 2 randomized clinical trial, high‑dose vitamin D3 added to standard treatment improved progression‑free survival (PFS) compared with standard‑dose vitamin D3 in patients with metastatic colorectal cancer (mCRC). OBJECTIVE: To determine if high‑dose vitamin D3 added to standard chemotherapy improves outcomes in patients with previously untreated mCRC. DESIGN, SETTING, AND PARTICIPANTS: Double‑blind phase 3 randomized clinical trial enrolling 455 patients with previously untreated mCRC, conducted in the US through the National Clinical Trials Network from October 2019 to December 2022 (database freeze: July 15, 2024). INTERVENTIONS: mFOLFOX6 or FOLFIRI plus bevacizumab every 2 weeks with either high‑dose vitamin D3 (8000 IU daily × 14 days as loading dose followed by 4000 IU daily) or standard‑dose vitamin D3 (400 IU daily) until disease progression, intolerable toxicity, or withdrawal of consent. MAIN OUTCOMES AND MEASURES: The primary endpoint was PFS assessed by the unstratified log‑rank test. Secondary endpoints included objective response rate, overall survival, and toxicity. RESULTS: Among 455 randomized patients (median age, 59 years; 181 [40%] female) with median follow‑up 20 months, the median PFS for high‑dose vitamin D3 (n = 228) was 11.8 months (95% CI, 10.3–13.3) vs 10.3 months (95% CI, 9.4–12.2) for standard‑dose vitamin D3 (n = 227) (1‑sided log‑rank P = 0.25). There were no significant differences in objective response rate between high‑dose and standard‑dose vitamin D3 (51% [95% CI, 44%–58%] vs 44% [95% CI, 37%–50%], respectively; P = 0.12), or in overall survival (median, 25.6 vs 27.0 months; 1‑sided log‑rank P = 0.66). CONCLUSIONS AND RELEVANCE: Among patients with previously untreated mCRC, addition of high‑dose vitamin D3, vs standard‑dose vitamin D3, to standard chemotherapy plus bevacizumab did not improve PFS.

Patients with metastatic colorectal cancer have limited effective and tolerable treatment options, especially after progression on multiple chemotherapy regimens. A new, orally available VEGFR inhibitor that significantly improves overall survival could substantially impact treatment paradigms.

Bizonyítékszint: Korai humán adat. Kis vagy feltáró emberi adat.

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