Randomized controlled trial on the skin toxicity of panitumumab in third-line treatment of KRAS wild-type metastatic colorectal cancer: HGCSG1001 (Japanese Skin Toxicity Evaluation Protocol with Panitumumab; J-STEPP).

Abstract

541 Background: Panitumumab (Pmab), a fully human monoclonal antibody targeting the EGFR, has been demonstrated the efficacy in patients with KRASwild-type metastatic colorectal cancer (mCRC). Though STEPP study (Lacouture et al, JCO 2010) showed that pre-emptive skin treatment reduced skin toxicities compared with reactive treatment among patients receiving Pmab, the data of Asians has not been reported. We planned a randomized controlled open-label trial to verify the differences between pre-emptive and reactive treatment for skin toxicities in Japanese patients. Methods: Patients receiving Pmab-containing treatments as third line regimen for mCRC were randomly assigned 1:1 to pre-emptive or reactive skin treatment group. In the pre-emptive treatment group, patients received skin moisturizers, sunscreen, topical steroid and minocycline. In the reactive treatment group, patients received only skin moisturizers. The primary endpoint was the cumulative incidence of ≥ grade 2 skin toxicities during the 6-week treatment period. Retrospectively, dermatologist reviewed skin toxicities with photographs in blinded manner. Results: Out of 95 enrolled patients, 47 patients were randomly assigned to pre-emptive group, and 48 to reactive group. The incidence of ≥ grade 2 skin toxicities during the 6-week treatment period (according to investigator’s assessment) was 21.3% and 62.5% (risk ratio [RR] = 0.34, 95% CI 0.19 - 0.62; p<0.001) for the pre-emptive and reactive treatment groups, respectively. A similar trend was observed in central review by dermatologist (18.6% and 50.0%, respectively [RR = 0.37, 95% CI 0.19 - 0.74; p = 0.002]). The concordance rate between them was 75.8%. Median time to first occurrence of ≥ grade 2 skin toxicities was not reached in the pre-emptive group and 3.2 weeks (95% CI 1.9 - 6.1) in reactive group (p < 0.001). Conclusions: The pre-emptive skin treatment could reduce the severity of the skin toxicities during the Pmab treatment. Our data clearly validate that the pre-emptive treatment is also recommended in Japanese patients. Clinical trial information: 000004883.