Effect of Primary Tumor Location on Second- or Later-line Treatment Outcomes in Patients With RAS Wild-type Metastatic Colorectal Cancer and All Treatment Lines in Patients With RAS Mutations in Four Randomized Panitumumab Studies

Abstract

These retrospective analyses have confirmed that RAS WT right-sided mCRC is associated with a poor prognosis, regardless of the treatment. RAS WT patients with left-sided tumors benefitted from the addition of panitumumab in second or later treatment lines. Further research is warranted to determine the optimum management of right-sided mCRC and RAS MT tumors.

First‐line therapy for metastatic colorectal cancer: Current perspectives and future directions

“…The analyses of two randomized studies involving panitumumab in the second and third lines demonstrated a trend to improved response rates and PFS with panitumumab regardless of tumor side in the second line when added to FOLFIRI (PFS HR = 0.88 for left sided and 0.75 for right sided). In comparison of third‐line treatment versus best supportive care, consistent with that seen in the C0‐17 study, the effect of panitumumab on PFS was greater for left‐ than right‐sided tumors (left sided: 5.5 months versus 1.6 months, HR = 0.31; P = < 0.001; right sided: 1.7 months versus 1.5 months, HR = 0.50; P = 0.1) . If, as guidelines suggest, EGFRmabs are increasingly used in first‐line in left‐sided RAS WT tumors, then this issue will be more relevant to RAS WT right‐sided tumors.…”

“…When considering the prognostic impacts of tumor side in second and subsequent treatment lines, the data are less consistent. In the second‐line 181 study investigating the addition of panitumumab to FOLFIRI, median OS in the FOLFIRI arm was 16.6 months versus 8.1 months in left‐ and right‐sided tumors, respectively . However, in the C0‐17 study that compared cetuximab and best supportive care in the third line, no prognostic differences between right‐ and left‐side tumors were found in the best supportive care arm .…”

The Impact of Primary Tumor Location in Synchronous Metastatic Colorectal Cancer: Differences in Metastatic Sites and Survival

“…2,4 There are several explanations for the differences in prognosis between primary tumor locations: (1) poorer response to systemic therapy of patients with RCC patients compared with patients with LCC; (2) higher frequency of signet-ring cell carcinoma and mucinous adenocarcinoma in RCC, which are associated with worse outcome; and (3) differences in metastatic patterns, which might influence survival as well. [5][6][7][8][9][10] The purpose of this study was to explore the differences in survival between primary tumor location in mCRC, hereby focusing on the role of metastatic sites using data from the Netherlands Cancer Registry.…”

Systemic treatment for metastatic colorectal cancer in the era of precision medicine

“…Further analysis of 200510181 was performed based on sidedness within the RAS wild‐type population . While no definitive difference in panitumumab activity was noted between left and right cancers in terms of PFS and OS, a significant differential activity was noted in RR on the panitumumab arm in left (RR 50% vs 13%) vs right‐sided cancers (13% vs3%) . In general, second‐line studies confirm the major downstaging impact of anti‐EGFR therapy within the RAS wild‐type population and its favorable impact on PFS within the RAS wild‐type mCRC population.…”

“…The small number of patients with right‐sided colon cancer with RAS wild‐type tumor in these 3 studies limits the ability to conclusively explore the impact of anti‐EGFR therapy in this population in refractory settings. Nonetheless, retrospective analyses from these randomized phase III studies and from other cases series and databases suggest minimal to no clinical benefit from integrating anti‐EGFR in this right‐sided RAS wild‐type population …”