Gastrointestinal Cancers

Published: Tuesday, May 25, 2010
New Research and Emerging Trends from the World Congress on Gastrointestinal Cancer

The 10th Annual Meeting of the World Congress on Gastrointestinal Cancer was held in Barcelona, Spain, in June. The Congress has grown into a key scientific program that covers malignancies affecting every component of the gastrointestinal tract and all facets of patient care, including screening, diagnosis, and management options for common and uncommon tumors.

As was pointed out at the meeting, the number of deaths from colorectal cancer has been dropping in recent years. Polyps are being found by screening and removed before they can develop into cancers. Screening is also allowing more colorectal cancers to be found earlier, when the disease is easier to cure. In addition, treatment for colorectal cancer has improved over the past decade, allowing for more effective options for people with this diagnosis.

Presentation of cutting-edge research has become one of the highlights of the World Congress on Gastrointestinal Cancer, offering opportunities for researchers to interact with colleagues and share their research with the community. Some of the key sessions are summarized in this issue.

Colorectal Cancer

KRAS Gene Status Predicts Outcome of First-line Treatment in Patients with Metastatic Colorectal Cancer

Eric Van Cutsem, MD, PhD, University Hospital Gasthuisberg, Leuven, Belgium, presented results from a subanalysis of the CRYSTAL study. The data show that patients with metastatic colorectal cancer are more likely to respond to first-line therapy of cetuximab (Erbitux) in combination with standard chemotherapy if they have wild-type KRAS tumors.

In 2007, the randomized phase III CRYSTAL trial showed that some patients with metastatic disease had longer progression-free survival (PFS) from FOLFIRI chemotherapy plus cetuximab than from FOLFIRI alone. Not all patients benefited, however, prompting the researchers to conduct a subanalysis to determine the influence of KRAS status on the outcome of initial combination therapy. The researchers analyzed archived tumor material from 578 of the 1,198 randomized patients enrolled in the CRYSTAL study. Of these, 540 samples were found to be KRAS-evaluable— 348 with normal KRAS status and the others with KRAS mutations— and were evaluated using PFS as the primary endpoint.

Of the patients with wild-type KRAS, 59% responded to chemotherapy with cetuximab, while 43% responded to chemotherapy alone. The mean PFS duration was 9.9 months for patients receiving combination therapy and 8.7 months for those getting FOLFIRI treatment alone.

The type of therapy given to patients with mutated KRAS status did not make much difference in the overall response rate (ORR) and PFS. The ORR for patients receiving combination therapy was 36%, compared with 40% for standard therapy. Initial combination treatment resulted in a mean PFS of 7.6 months, while chemotherapy led to 8.1 months.

The results indicate that KRAS status could be an important predictor of the effectiveness of metastatic colorectal cancer treatment. “KRAS is the first molecular marker for targeted therapy in combination with standard chemotherapy as a first-line treatment for metastatic colorectal cancer,” said Dr. Van Cutsem. “If we know in advance that a patient has a KRAS mutation, then we know we don’t have to treat the patient [with these agents].”

Bevacizumab Shows Benefit in Metastatic Colorectal Cancer Independent of KRAS Mutation Status

A team of researchers from Genentech, Inc., San Francisco, California, and Duke University, Durham, North Carolina, conducted a placebo-controlled phase III trial examining the benefits of bevacizumab (Avastin) in patients with metastatic colorectal cancer. Their findings, presented by Herbert Hurwitz, MD, Duke University Medical Center, indicate that the clinical benefits of the drug are similar in patients with KRAS wild-type tumors and mutant KRAS tumors.

Studies have shown that KRAS mutations, present in an estimated 30% to 40% of colorectal tumors, make it unlikely for patients to benefit from drugs such as cetuximab (Erbitux) that inhibit the activity of the epidermal growth factor receptor protein, which is often overactive in colorectal cancer. Bevacizumab, in contrast, works by destroying blood vessels that the tumors need to grow.

Dr. Hurwitz and his team of researchers microdissected tumor samples from 230 patients who were enrolled in a large, placebo-controlled randomized phase III study of irinotecan/fluorouracil/leucovorin (IFL) given with or without bevacizumab. Of this population, 129 patients received combination treatment while 101 were given placebo. The tumor samples were subjected to DNA sequence analysis for KRAS mutation, and researchers retrospectively measured progression-free survival (PFS), overall survival (OS), and objective response rate.

Among the 152 patients with wild-type KRAS tumors, median PFS was 13.5 months in the group getting IFL bevacizumab, compared with 7.4 months for the group getting IFL plus placebo, corresponding to a hazard ratio (HR) of 0.44. For the 78 patients with mutant KRAS, the IFL bevacizumab group had median PFS of 9.3 months, while those in the placebo group had a median PFS of 5.5 months (HR = 0.41).

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