#ESMOGI26# An interesting exploratory analysis from ATOMIC asks an important question: How much chemotherapy do patients receiving adjuvant FOLFOX + atezolizumab actually need? (Remember, this is our only adjuvant prospective study in MSI-H CRC and is with FOLFOX + Atezolizumab vs FOLFOX. If you can catch these patients before surgery, almost certainly better to treat neoadjuvantly). Quick takeaways: • Patients receiving >6 cycles of FOLFOX appeared to derive the greatest DFS benefit from the addition of atezolizumab (adjusted HR 0.45). • That benefit was not apparent among patients receiving ≤6 cycles (HR 0.84), although this subgroup was relatively small. • Receiving ≥12 cycles of atezolizumab was associated with numerically better DFS than shorter treatment, but this analysis is difficult to interpret given treatment discontinuation for toxicity and other confounders. My interpretation: This actually makes biological sense. Atezolizumab has consistently appeared less active than PD-1 inhibitors in MSI-H CRC. If that's true, then maintaining adequate chemotherapy intensity may be particularly important in this regimen. I don't think these exploratory data answer whether 3 months of CAPOX is sufficient in dMMR disease. If anything, they reinforce that ATOMIC should probably be viewed as the regimen that was studied, than the exact regimen used in clinical practice. Slides nabbed from @GillSharlene @TheGutOncLab @OncoAlert @Onco_Nexus @ESMO

#ESMOGI2026# Surprising news for mCRC out of ESMOGI. KRYSTAL-10: Adagrasib + cetuximab misses its primary endpoint in 2L KRAS G12C mCRC. After the accelerated approval and encouraging activity from KRYSTAL-1, many expected dual KRAS/EGFR inhibition to outperform chemotherapy in the second line. That didn't happen. Quick hits: • Primary endpoint (PFS): Negative • mPFS 7.5 vs 8.1 months • HR 0.89 (95% CI 0.71-1.13) • Response rate dramatically improved • ORR 47% vs 16% • CR 7% vs <1% • No improvement in OS at the final analysis despite the higher response rate. So what happened? This is a reminder that response rate ≠ durable disease control. Nearly half of patients responded, but those responses did not translate into longer PFS or OS compared with modern chemotherapy. Targeted therapy works, but mCRC can overcome via resistance mechanisms (such as via massive KRAS upregulation). Will be interesting to see how novel degraders come into the mix here... Remember, this is a first gen KRASi, the future is still bright here. What does this mean for clinic tomorrow? Honestly, I still love a chemo-free option that is at least on par with chemotherapy. This isn't the end of KRAS G12C in CRC. Far from it. The focus now shifts to moving targeted therapy earlier, where combinations with chemotherapy may produce deeper, more durable responses before resistant clones emerge. Multiple frontline studies are already underway. @TheGutOncLab @OncoAlert @Onco_Nexus @myESMO