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Purpose The AIO KRK-0104 randomized phase II trial investigated the efficacy and safety of cetuximab combined with capecitabine and irinotecan (CAPIRI) or capecitabine and oxaliplatin (CAPOX) in the first-line treatment of metastatic colorectal cancer (mCRC). Patients and Methods A total of 185 patients with mCRC were randomly assigned to cetuximab (400 mg/m2 day 1, followed by 250 mg/m2 weekly) plus CAPIRI (irinotecan 200 mg/m2, day 1; capecitabine 800 mg/m2 twice daily days 1 through 14, every 3 weeks; or cetuximab plus CAPOX (oxaliplatin 130 mg/m2 day 1; capecitabine 1,000 mg/m2 twice daily day 1 through 14, every 3 weeks). The primary study end point was objective response rate (ORR). Results In the intention-to-treat patient population (n = 177), ORR was 46% (95% CI, 35 to 57) for CAPIRI plus cetuximab versus 48% (95% CI, 37 to 59) for CAPOX plus cetuximab. Analysis of the KRAS gene mutation status was performed in 81.4% of the intention to treat population. Patients with KRAS wild-type in the CAPIRI plus cetuximab arm showed an ORR of 50.0%, a PFS of 6.2 months and an OS of 21.1 months. In the CAPOX plus cetuximab arm, an ORR of 44.9%, a PFS of 7.1 months and an OS of 23.5 months were observed. While ORR and PFS were comparable in KRAS wild-type and mutant subgroups, a trend toward longer survival was associated with KRAS wild-type. Both regimens had manageable toxicity profiles and were safe. Conclusion This randomized trial demonstrates that the addition of cetuximab to CAPIRI or CAPOX is effective and safe in first-line treatment of mCRC. In the analyzed regimens, ORR and PFS did not differ according to KRAS gene mutation status.

3588 Background: This study investigated the impact of early tumor-shrinkage (ETS) on progression-free (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated within the AIO KRK-0104-trial. ETS was previously shown to be a predictor of treatment response to cetuximab. The present analysis, for the first time, evaluates the correlation of ETS with outcome parameters in patients undergoing capecitabine-based therapy. It also aims to correlate the predictive value of ETS and cetuximab-induced skin toxicity. Methods: The AIO KRK0104 trial was performed as a randomised study comparing capecitabine/oxaliplatin (CAPOX) plus cetuximab to capecitabine/irinotecan (CAPIRI) plus cetuximab in the first-line treatment of mCRC. 121 patients were available for evaluation of ETS at 6 weeks. ETS was defined as a relative change of ≥20% in the sum of the longest diameters of target lesions compared to baseline. Results: Tumors of 63 patients (71% KRAS wild-type (wt), 100% skin reactions) developed ETS, 58 tumors did not develop ETS (53% KRAS wt, 86% skin reactions). ETS was associated with prolonged PFS (8.9 vs. 4.7 months, p-line therapy ETS correlates with prolonged PFS and OS. ETS also correlates with cetuximab-induced skin toxicity. Both parameters may therefore serve as post-randomisation surrogate markers of favourable outcome for cetuximab-based treatment.

3589 Background: The AIO KRK-0104 randomized phase II trial investigated the efficacy and safety of two capecitabine-based regimens: CAPIRI plus cetuximab (CAPIRI-C) and CAPOX plus cetuximab (CAPOX-C) in the first-line treatment of metastatic colorectal cancer (mCRC). Treatment related skin toxicity was evaluated separately for capecitabine and cetuximab. The present analysis investigates the correlation of capecitabine-attributed skin toxicity (Cape-ST) and parameters of treatment efficacy. Methods: mCRC patients were randomized to cetuximab (400mg/m2 day 1, followed by 250mg/m2 weekly) plus CAPIRI (irinotecan 200mg/m2, day 1; capecitabine 800mg/m2 twice daily, days 1-14, every 3 weeks) or cetuximab plus CAPOX (oxaliplatin 130mg/m2 day 1; capecitabine 1000mg/m2 twice daily, days 1-14, every 3 weeks). Results: Of 185 recruited patients, 149 patients (CAPIRI-C, n=78; CAPOX-C, n=71) received study treatment beyond the first tumor assessment and were evaluable for efficacy. While cetuximab-specific skin toxi...