165 Background: Metastatic colorectal cancer (mCRC) is subdivided based on sidedness and molecular characteristics to guide selection of EGFR targeting. The use of EGFR inhibitors (EGFRi) with monoclonal antibodies panitumumab and cetuximab remains standard of care with use largely in combination with chemotherapy. Retrospective data has suggested limited tumor bulk as an independent biomarker for durable response to EGFRi. This study evaluates the clinical activity of EGFRi in early line RAS/RAF wildtype (wt) L-sided non-bulky mCRC. Methods: A prospective phase II clinical trial of investigator choice EGFRi was performed to evaluate early line activity (NCT04587128). Subjects were eligible in 1L or 2L setting for subjects with left-sided, non-bulky metastases (no metastatic lesion >35mm), and KRAS/NRAS/BRAF V600 wt. Toxicities were graded according to CTCAE v5.0. Response was evaluated according to RECIST v1.1 criteria by treating investigator. Dosing was performed per FDA labeling of panitumumab 6mg/kg or cetuximab 500mg/kg IV days 1 and 15. The primary objective for efficacy of early line EGFRi was disease control rate at 6 months. Results: Between 11/2020 to 12/2024, 21 patients (8 females, median age 53 years, ECOG PS 0-1) were treated on study. 14/21 subjects had measurable disease at time of enrollment per RECIST v1.1 (66.7%). A majority of subjects had received prior systemic chemotherapy in adjuvant or 1L metastatic setting (19/21; 90.5%). The most common toxicity to EGFRi included events of G4 hypomagnesemia (9.5%), as well as, G3 lymphopenia (14.2%) and acneiform rash (9.5%). 14 subjects were evaluable for response assessment. Responses included complete response in 1/14 (7.1%) patients, partial response in 9/14 (64.3%), and stable disease in 4/14 (28.6%). The primary endpoint of 6-month DCR was met in 14/21 subjects (66.7%). Median progression free survival (PFS) was 7.5 months with all subjects followed to completion of study endpoint. One subject stopped therapy due to significant response facilitating procedural intervention. At the 6 month time point, subjects not remaining on came off for progressive disease (4/21,19.0%) or adverse events (2/21, 9.5%). Conclusions: Single agent EGFRi achieved 7.5 month PFS and exceeded target landmark for 6-month DCR in early line therapy for subjects with KRAS/NRAS/BRAF V600 wt, non-bulky, left-sided mCRC. This treatment offers a non-chemotherapy containing option and could enhance the EGFRi retreatment potential, which is being evaluated in additional cohorts. Clinical trial information: NCT04587128 .
Kratz et al. (Sat,) studied this question.