Tumor bulk as an independent marker of anti-EGFR therapeutic benefit in metastatic colorectal cancer

e15054 Background: Molecular testing and location of the primary tumor (right-sided (R) versus (vs) left-sided (L)) are useful in predicting the clinical benefit of the anti-epidermal growth factor receptor (EGFR) antibodies, cetuximab (cet) and panitumumab (pan), in metastatic colorectal cancer (mCRC). We hypothesized that tumor bulk might also be predictive of treatment benefit given the potential for increased intra-tumor heterogeneity and reduced penetration of antibodies into bulkier lesions. Methods: A single institution retrospective cohort of 69 patients (pts) with KRAS wild-type mCRC were identified who received either cet or pan in the late-line setting +/- chemotherapy. Metastatic sites were cataloged including independent review of CT imaging prior to initiation of anti-EGFR therapy. Disease bulk was defined categorically as single metastatic lesion with diameter measuring > 3.0 cm. Results: This cohort represents a diverse group having received varying prior lines of therapy and having assorted disease sites including mediastinal, pulmonary, hepatic, omental, and osseous lesions. When treated with anti-EGFR therapies, pts with pre-treatment metastases ≤3.0 cm in diameter had significant improvement in median progression free survival (mPFS) (6.2 months (mos)) vs pts with metastases > 3.0 cm (3.9 mos, p < 0.01). A trend towards improvement in overall survival was observed for pts with non-bulky (15.8 mos) vs bulky disease (8.6 mos, p = 0.08). A trend towards increased mPFS existed in L (5.1 mos) vs R cancers (2.5 mos, p = 0.11). In R cancers, no significant difference in mPFS was noted between bulky (2.5 mos) and non-bulky disease (2.9 mos, p = 0.53). Non-bulky L cancers had a significantly improved mPFS of 7.5 mos compared to 3.9 mos with L bulky disease (p < 0.01). Non-bulky L cancers trended towards improved overall survival of 17.0 mos compared to 9.6 mos with L bulky disease (p = 0.08). Conclusions: Despite limited small sample size, these data indicate that tumor bulk is a potential predictor of the therapeutic benefit of anti-EGFR agents in left-sided mCRCs across a heterogeneous pt population. Disease bulk deserves further evaluation in larger datasets of mCRC across targeted therapeutics.