Location of Primary Tumor Predicts Survival and Choice of Treatment in Metastatic Colorectal Cancer

SUMMARY: ColoRectal Cancer (CRC) is the third most common cancer diagnosed in both men and women in the United States. The American Cancer Society estimates that approximately 135,000 new cases of ColoRectal Cancer will be diagnosed in the United States in 2016 and over 49,000 patients are expected to die of the disease. Even though prognosis for patients with Colon Cancer has improved over the past two to three decades, it has remained unclear if improvement in survival was greater for left sided Colon Cancer versus cancer originating in the Right hemicolon.

Venook and colleagues had previously presented data from the primary analysis of a phase III CALGB/SWOG 80405 study which compared AVASTIN®: (Bevacizumab) or ERBITUX® (Cetuximab), given in conjunction with FOLFOX (Leucovorin, 5-Fluorouracil, Oxaliplatin) or FOLFIRI (Leucovorin, 5-FU, Irinotecan), as first line treatment of metastatic colorectal cancer. This study showed that chemotherapy plus ERBITUX® resulted in similar Overall Survival (29.9 months) as chemotherapy plus AVASTIN® (29 months) as well as Progression Free Survival (PFS). The present publication is a retrospective evaluation from the phase III 80405 clinical trial which included data from 1,025 patients with KRAS wild-type disease. The researchers assessed the impact of tumor location on Overall and PFS in this group of patients. The median age was 59 yrs and 293 patients had a right-sided primary tumor (location in the cecum to hepatic flexure) and 732 patients had a left-sided primary tumor (location in the splenic flexure to rectum).

It was noted that patients with tumors originating in the right side of the colon had much shorter median Overall Survival (19.4 months) compared to patients with left-sided tumors (33.3 months), (HR=1.60; P<0.001), with a 14 month survival improvement in the left versus right-sided primary tumors, for patients with metastatic disease. Tumor location in the colon also had a bearing on response to ERBITUX® and AVASTIN®. For the patient group who received ERBITUX®, the median Overall Survival (OS) was 36 months for patients with left-sided tumors but 16.7 months for patients with right-sided tumors. For those who received AVASTIN®, the median OS was 31.4 months for patients with left-sided tumors and 24.2 months for those with right-sided tumors. The median PFS was also influenced by the site of the primary tumor and was 8.9 months for right-sided tumors versus 11.5 months for left-sided tumors in the overall cohort of patients (HR = 1.26; P = 0.002). In a separate analysis, the authors also evaluated data from an additional 213 patients in CALGB/SWOG 80405 study who harbored KRAS mutations. These patients were originally included in this study prior to knowledge that ERBITUX® only benefited KRAS wild-type tumors. In this group of patients, those with left-sided primary tumors again achieved a longer median OS (30.3 months) compared to 23.1 months, among patients with right-sided tumors.

It was concluded that the biology of tumors originating in the right colon may be different from those originating in the left colon with ERBITUX® showing superiority over AVASTIN® when combined with chemotherapy in KRAS wild-type patients with left-sided colon cancer, whereas patients with right-sided colon cancer appear to benefit more from AVASTIN® based chemotherapy regimen. Regardless of KRAS mutational status, AVASTIN® based, first line chemotherapy regimen should be considered, for all patients with metastatic colorectal cancer, with a right-sided primary tumor. Impact of primary (1º) tumor location on overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405 (Alliance). Venook AP, Niedzwiecki D, Innocenti F, et al. J Clin Oncol 34, 2016 (suppl; abstr 3504)