Primary tumor site matters in metastatic colorectal cancer

Last Updated: 2017-09-27

By Marilynn Larkin

NEW YORK (Reuters Health) - Location of the primary tumor is associated with both response to biologic therapy and survival in patients with metastatic colorectal cancer (mCRC), researchers in California say.

Recent studies suggest that whether the primary tumor is on the right or left side of the colon affects survival and response to therapies such as bevacizumab or cetuximab, according to Dr. Maheswari Senthil of Loma Linda University and colleagues.

To investigate this possibility in a diverse mCRC population, the team reviewed data from the California Cancer Registry of mCRC patients who were treated with systemic chemotherapy (SC) alone, or with SC and biologic therapy, from 2004 through 2014. Patients were stratified by primary tumor location.

As reported online September 20 in JAMA Surgery, of the 11,905 patients (mean age, 60; 56% men) eligible for the study, 4,632 received SC and biologic therapy.

Compared with SC alone, SC plus bevacizumab reduced mortality among people with right- and left-sided mCRC. SC plus cetuximab, in contrast, reduced mortality relative to SC alone only in patients with left-sided tumors, and the SC/cetuximab combination was associated with significantly higher mortality in people with right-sided tumors.

Among patients treated with SC plus biologic therapy, right-sided tumor origin was associated with significantly higher mortality for those receiving bevacizumab (HR, 1.31) or cetuximab (HR, 1.88), compared with left-sided tumor origin.

Among the 668 patients with wild-type KRAS tumors, cetuximab was associated with significantly reduced mortality compared with bevacizumab only among people with left-sided mCRC (HR, 0.75). Further, compared to patients with left-sided mCRC, those with right-sided disease had more than twice the mortality risk (HR, 2.44).

Summing up, the authors observe, "Right-sided primary tumor location is associated with higher mortality regardless of biologic therapy type. In patients with wild-type KRAS tumors, treatment with cetuximab benefited only those with left-sided mCRC and was associated with significantly poorer survival among those with right-sided mCRC."

"It is of paramount importance for oncologists to recognize the biologic differences between right and left colon cancer to avoid utilizing costly and ineffective treatment in the management of patients with stage IV colon cancer," Dr. Senthil stressed in an email to Reuters Health.

"Ongoing research will help elucidate the differences between right and left colon cancer and (inform) the development of a customized and an effective treatment strategy based on the primary tumor location," he concluded.

Dr. Eric Nakakura of the University of California, San Francisco, author of a related editorial, told Reuters Health, "Today, there is much talk about the promise of precision cancer medicine to bring the most personalized care to patients."

"This and other recent studies that have analyzed large data (sets) provide compelling evidence that where a colon cancer arises - right versus left - directly impacts patient prognosis and predicts response to therapy," he said by email.

"Recent advances in collecting and analyzing large data (sets) in other cancers will also likely lead to increasingly personalized treatments for patients in the near future," he concluded.

SOURCES: http://bit.ly/2wWh8Lz and http://bit.ly/2hybTvK

JAMA Surg 2017.