Clinical Edge Journal Scan

RAS/TP53-mutant mCRC: Adavosertib shows promise in phase 2


 

Key clinical point: Adavosertib vs active monitoring (AM) following induction chemotherapy showed a significant progression-free survival (PFS) advantage along with a favorable safety profile in patients with RAS/TP53-mutant metastatic colorectal cancer (mCRC).

Major finding: Adavosertib showed significant PFS advantage over AM (3.61 months vs 1.87 months; adjusted hazard ratio, 0.35; P = .0022). The frequency of diarrhea (61% vs 28%), fatigue (75% vs 56%), nausea (68% vs 32%), and vomiting (41% vs 4%) were higher in adavosertib than AM arms, with majority being low grade.

Study details: Findings are from FOCUS4-C, a phase 2 trial including patients with RAS/TP53-mutant mCRC who had stable disease or response at the end of 16-week induction chemotherapy and were further randomly assigned to AM (n=25) or adavosertib (n=44).

Disclosures: FOCUS4-C was cofunded by the MRC/NIHR Efficacy and Mechanism Evaluation program and CRUK. AstraZeneca provided drug supply and distribution of adavosertib and an educational grant. The authors declared receiving honoraria, research funding, travel and accommodation expenses, and/or consulting/advisory roles from various sources including AstraZeneca.

Source: Seligmann JF et al. J Clin Oncol. 2021 Sep 18. doi: 10.1200/JCO.21. 01435 .

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