Gastrointestinal tumours, colorectal 1


Inhibition of WEE1 is effective in TP53 and RAS mutant metastatic colorectal cancer (mCRC): A randomised phase II trial (FOCUS4-C) comparing Adavosertib (AZD1775) with active monitoring

Seligmann, et al.


In this phase II randomised trial, Adavosertib improved PFS compared with AM and demonstrates potential as a well-tolerated therapy for RAS/TP53-mutant mCRC. Activity was greater in patients with left-sided tumours, with potential impact on OS. Further testing is required in this sizable population of unmet need.



Exploratory Biomarker Analysis of DESTINY-CRC01, a Phase 2, Multicenter, Open-Label Study of Trastuzumab Deruxtecan (T-DXd, DS-8201) in Patients (pts) With HER2-Expressing Metastatic Colorectal Cancer (mCRC)

Siena, et al.


This exploratory analysis of biomarker data in HER2+ mCRC pts administered T-DXd indicates that antitumor activity appears to be correlated with BL HER2 expression or amplification in tumor and liquid biopsy. Further investigations into potential mechanisms of resistance to and patient selection for T-DXd in HER2+ mCRC are warranted.



FOLFOXIRI plus bevacizumab (bev) plus atezolizumab (atezo) versus FOLFOXIRI plus bev as first-line treatment of unresectable metastatic colorectal cancer (mCRC) patients: results of the phase II randomized AtezoTRIBE study by GONO

Cremolini, et al.


The primary endpoint was met: the addition of atezo to FOLFOXIRI/bev prolongs PFS of mCRC patients. While the magnitude of benefit is significantly higher in dMMR tumors, signals of efficacy are reported also in the pMMR subgroup. Translational analyses to identify predictive biomarkers are ongoing.



MAYA trial: temozolomide (TMZ) priming followed by combination with low-dose ipilimumab and nivolumab in patients with microsatellite stable (MSS), MGMT silenced metastatic colorectal cancer (mCRC)

Pietrantonio, et al.


MAYA study proved the immune-sensitizing role of TMZ in MSS/MGMT silenced mCRC. The safety and efficacy of TMZ priming followed by ipilimumab/nivolumab combo strategy is worthy of further development and extensive biomarker analyses are ongoing.