Left-Side Primary Tumors Predict Longer Survival in Metastatic CRC

The physical location of the primary tumor predicts survival in patients with metastatic colorectal cancer (mCRC), according to a retrospective analysis of a large study. Patients with left-side tumors-those originating in the descending colon, the sigmoid colon, or the rectum-survive significantly longer than those with tumors originating on the right side, in the ascending colon or the cecum.

“While previous studies had suggested that tumor location may impact clinical colorectal cancer outcomes, the effect we observed in this analysis appears to be far greater than we expected,” said lead author Alan P. Venook, MD, of the University of California, San Francisco, in a press release.

The study included patients from the phase III Cancer and Leukemia Group B (CALGB)/Southwest Oncology Group (SWOG) 80405 clinical trial that compared bevacizumab and cetuximab in combination with chemotherapy as first-line treatment of mCRC, and found no difference between the drugs; there were 293 patients with right-side primary tumors and 732 patients with left-side primary tumors. The results (abstract 3504) will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, on June 5 in Chicago, and were discussed on Wednesday in a press call with reporters.

Patients with left-side tumors had a median overall survival (OS) of 33.3 months, compared with only 19.4 months in those with right-side tumors, yielding a hazard ratio (HR) of 1.60 (95% CI, 1.37–1.86; P < .001).

Among only those patients treated with cetuximab, the difference was most pronounced. Those with left-side tumors had a median OS of 36.0 months, compared with 16.7 months for patients with right-side tumors, for an HR of 1.987 (95% CI, 1.60–2.46; P < .001). In contrast, bevacizumab-treated patients had an OS of 31.4 months with a left-side tumor and 24.2 months with right-side tumors. These results suggest that patients with right-side tumors will get little benefit from cetuximab.

Progression-free survival (PFS) was similar, with a median PFS of 11.5 months in those with left-side tumors and 8.9 months in those with right-side tumors, for an HR of 1.26 (95% CI, 1.096–1.453; P = .002).

The investigators also conducted a separate analysis of 213 patients from the FIRE-3 study with KRAS mutations, which is now known to be an important factor in the use of cetuximab. In that group, patients with left-side tumors survived longer (30.3 months) than those with right-side tumors (23.1 months).

“These findings will likely change the way we approach colorectal cancer treatment and research, even as we seek to more deeply understand the biology driving the difference in outcomes between right- and left-sided cancers,” said Venook. He noted during the press call that the side of the tumor is likely a surrogate marker for some difference in underlying biology, and that an ongoing molecular analysis of tissues from this trial could help explain that difference.

ASCO president Julie M. Vose, MD, noted that this is the largest study to date of tumor location in CRC. “It strongly suggests that this unexpected factor could answer some long-standing questions about why certain patients do better than others,” she said in the press release. “It is also an important reminder, in this exciting era of precision medicine, that genomics is not the only source of insight into how cancers should be studied and treated.”