GASTROINTESTINAL CANCER

Can a Biomarker Predict Therapeutic Efficacy in Metastatic Colorectal Cancer?
You have heard of designer drugs and designer jeans, but what about “designer genes”? The KRAS gene mutation status has been shown to have predictive value for treatment with cetuximab plus FOLFIRI chemotherapy in the first-line therapy of patients with metastatic colorectal cancer (mCRC) in the phase III CRYSTAL trial. KRAS mutation status (normal or wild-type [wt] vs. mutated [mt]) was determined in the tumor tissue of 540 patients, and a retrospective analysis was done to evaluate the impact of the KRAS mutations. Treatment was FOLFIRI alone vs. cetuximab plus FOLFIRI (F+C) and primary endpoint was PFS with secondary endpoint RR. Results: PFS for all 1,198 patients favored F+C (HR=0.85, p=0.048) and RR 47% F+C vs. 39% F alone. KRAS wild-type (wt) PFS=HR 0.68, p=0.017 and PFS for KRAS mt (mutant type) HR=1.07, p=0.47; RR for KRAS wt 59% F+C vs. 43% for F alone (p=0.0025) and RR in KRAS mt 36.2% F+C vs. 40.2% F alone.

Conclusion: This large study shows that addition of cetuximab to FOLFIRI significantly increases the PFS compared to chemotherapy alone. The data demonstrate that the treatment effect of cetuximab in patients with KRAS wt is significantly enhanced compared to FOLFIRI alone, whereas patients with KRAS mt do not benefit from C+F. Cetuximab + FOLFIRI could now be considered a first-line option for mCRC in those with KRAS wild-type mutation.
Abstract #2 E. Van Cutsem, et al. Plenary Session-J Clin Oncol 26: 2008

Adjuvant Chemotherapy for Resectable Pancreatic Cancer:
Is There Light at the End of the Tunnel?
Final results of CONKO-001, a randomized phase III trial of adjuvant chemotherapy with gemcitabine vs. observation in 354 eligible patients with resected pancreatic cancer (PC), were presented. After stratification for complete (RO or R1) resection, nodal involvement, and tumor stage patients were randomized to receive either gemcitabine (G) 1 g/m2 d1, 8, and 15 every 4 weeks for 6 months or observation (O). Primary endpoint was DFS, with secondary endpoints OS and toxicity. Results: The analyses confirm significant improvement for G in median DFS (G: 13.4 months, O: 6.9 months, p<0.001). Estimated DFS at 3 and 5 years was 23.5% and 16.0% in G vs. 8.5% and 6.5% in the O group. G significantly improves median OS (G: 22.8 months, O: 20.2 months, p=0.005). Estimated survival at 3 and 5 years was 36.5% and 21.0% for G patients vs. 19.5% and 9.0% for O group patients.

Conclusion: Treatment with gemcitabine for 6 months in patients after complete resection of PC significantly increases DFS and OS compared with O alone. Impressive results in this disease. I think we do see a light.
LBA4504 P. Neuhaus, et al. J Clin Oncol 26: 2008