Survival by sidedness of metastatic colorectal cancer (mCRC) treated with epidermal growth factor receptor antibodies (EGFR-Ab) in the refractory setting: A population-based study of 1509 patients

Background: Sidedness of primary is an established prognostic factor in mCRC and recently has been shown to be an important predictive factor for patients (pts) treated with EGFR-Ab (always in combination with chemotherapy) in 1st and 2nd line settings. Limited data is available in 3rd line and beyond, where EGFR-Ab are used either as monotherapy or with chemotherapy. In Ontario, Canada, public funding of EGFR-Ab is restricted to chemorefractory disease. This study examines the impact of sidedness on overall survival (OS) in chemorefractory mCRC treated with EGFR-Ab monotherapy and combination. Methods: This population-based retrospective cohort study used linked data from the Institute for Clinical Evaluative Sciences to evaluate mCRC pts treated in Ontario with EGFR-Ab from Jan 2006-Dec 2014. Over 99% of cases are captured via the Ontario Cancer Registry. The primary outcome was OS. Monotherapy v combination was compared by panitumumab (pani; funded only as monotherapy) v cetuximab (cet; funded only with chemotherapy) outcomes. Sidedness was determined by ICD-10 code as right (R; including transverse colon) or left (L). Results: Of 67117 CRC pts,1553 received EGFR-Ab for refractory mCRC (429 R, 1080 L, 44 unknown). 71% received pani. R were more commonly female, with significantly shorter time (months, m) from diagnosis to EGFR-Ab therapy (mean±SD: 28.7±18.3 v 32.8±19.2; p<0.001). Median OS for R with any EGFR-Ab therapy was significantly worse than L: 30.5 v 39.3m(HR 1.22; 95% CI 1.07-1.38; p=0.0026); this was true for monotherapy (HR 1.22; 95% CI 1.05-1.42, p=0.0089) with a nearsignificant trend for combination (HR 1.30; 95% CI 0.99-1.7, p=0.055). For L, OS was identical between monotherapy and combination; for R there was a near-significant trend to longer survival with combination (HR 0.76; 95% CI 0.58-1.01, p=0.058). Conclusions: This large population cohort demonstrates that R sidedness is significantly predictive for survival with EGFR-Ab in refractory mCRC, consistent with findings in earlier lines of therapy. The differences are particularly seen with monotherapy. L sided cancers appear to benefit equally from monotherapy as combination.