Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer

Rákkutatás · Pancreatic cancer · KRAS

Daraxonrasib significantly improves overall survival (13.2 months vs 6.7 months) and progression‑free survival (7.2 months vs 3.6 months) compared with investigator‑chosen chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC), especially those with RAS G12 mutations.

Background: Patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC) have limited options. Aberrant activation of the RAS pathway is the key driver of PDAC, with oncogenic RAS mutations present in >90% of cases. Daraxonrasib is an oral, tri‑complex inhibitor of mutant and wild‑type RAS in its active GTP‑bound state. Methods: In a phase 3, international, open‑label, randomized trial, 500 patients with previously treated mPDAC were assigned to daraxonrasib (n=248) or investigator‑chosen chemotherapy (n=252). Primary endpoints were overall survival (OS) and progression‑free survival (PFS) in the RAS G12 population; secondary endpoints included OS and PFS in the overall population, objective response, and patient‑reported quality of life. Results: In the RAS G12 population, median OS was 13.2 months with daraxonrasib vs 6.6 months with chemotherapy (hazard ratio 0.40, P<0.001). In the overall population, median OS was 13.2 months vs 6.7 months (HR 0.40, P<0.001). Median PFS was 7.3 months vs 3.5 months for daraxonrasib vs chemotherapy in the RAS G12 group (HR 0.45, P<0.001), and 7.2 months vs 3.6 months in the overall group (HR 0.49, P<0.001). Grade ≥3 adverse events occurred in 61.8% of the daraxonrasib group and 69.6% of the chemotherapy group; treatment‑related discontinuations were 1.2% vs 11.2%. Conclusion: Daraxonrasib confers a clinically meaningful survival advantage over chemotherapy in previously treated mPDAC, particularly in patients with RAS G12 mutations.

This study demonstrates that targeting the RAS pathway with daraxonrasib offers a durable survival benefit in a disease traditionally refractory to therapy, providing a new therapeutic option for patients with metastatic pancreatic cancer.

Bizonyítékszint: Irányelv / elfogadott gyakorlat. Magas szintű klinikai elfogadottság.

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