A phase II, open-label trial of skin toxicity (ST) evaluation (STEPP) in metastatic colorectal cancer (mCRC) patients (pts) receiving panitumumab (pmab) + FOLFIRI or irinotecan-only chemotherapy (CT) as 2nd-line treatment (tx): Interim analysis

Abstract

15007 Background: Pmab, a fully human monoclonal antibody against the epidermal growth factor receptor, is approved in the US for the tx of pts with refractory mCRC. This randomized study examined differences between pre-emptive and reactive skin tx for ST associated with pmab therapy. Methods: Pts with unresectable mCRC and disease progression whose 1st-line tx with CT± bevacizumab failed were enrolled. Pts received Q2W FOLFIRI+pmab (6.0mg/kg) or Q3W irinotecan+pmab (9.0mg/kg). Within cohorts, pts were randomized 1:1 to pre-emptive ST tx (24 hrs prior to 1st pmab dose, daily through wk 6) or reactive tx (after ST developed). ST tx included use of skin moisturizers, sunscreen, topical corticosteroids, and oral doxycycline. The primary endpoint was incidence of specific ≥ grade (gr) 2 ST during the 6-wk skin tx period. This early analysis assessed pooled safety (data cutoff 06/07). Results: Of 58 pts with available data, 32 pts and 26 pts received the Q2W and Q3W regimens, respectively. Pts received a median of 7.5 (Q2W cohort) and 4.0 (Q3W cohort) doses of pmab and CT. Tx-related adverse events (AEs) were seen in 95% of pts; 62% had gr 3/4. AEs of interest are shown (table). Pmab dose reductions occurred in 6 pts (10%) due to ST; 19 pts had serious AEs; 2 pts ended the study because of an AE. Ten pts (31%) in the Q2W cohort and 1 pt (4%) in the Q3W cohort had an objective response to pmab. Planned enrollment of 95 pts has been completed; efficacy outcomes (pre-emptive vs reactive ST tx and objective response) by KRAS status for all pts will be presented. Conclusions: No safety issues were identified in this early analysis of pts receiving pmab + irinotecan-based CT. Pooled Analysis of Adverse Events (n = 58) AE Any grade, n (%) ≥ Grade 3, n (%) Skin Toxicity 51 (88) 13 (22) Infections * 42 (72) 13 (22) Diarrhea 40 (69) 8 (14) Nausea 31 (53) 4 (7) Neutropenia 16 (28) 9 (16) Dehydration 13 (22) 7 (12) Hypomagnesemia 10 (17) 3 (5) Deep venous thrombosis 2 (3) 2 (3) Pulmonary embolism 0 (0) 0 (0) Per MedDRA; grading based on CTCAEv3, modified for ST. * Includes rash pustular and paronychia No significant financial relationships to disclose.