Highlights from the 2014 Gastrointestinal Cancers Symposium

Feb 25, 2014


Andrew X. Zhu, MD, PhD, discusses Abstract 172 “EVOLVE-1: Phase 3 study of everolimus for advanced HCC that progressed during or after sorafenib.”

The 2014 Gastrointestinal Cancers Symposium was held January 16-18, in San Francisco, California. The following highlights are courtesy of the Gastrointestinal Cancers Symposium Daily News team (gicasym.asco.org/dn).

This year marked the 11th anniversary of the annual Gastrointestinal (GI) Cancers Symposium, which had a record attendance of 3,400 clinicians and researchers from across the oncology field. Since the meeting's founding in 2003, thousands of people from around the world have attended the Symposium to learn about state-of-the art advances in the management of GI cancers. This year's Symposium was marked by exciting new research and advances in colorectal, esophagus and stomach, and pancreatic and hepatobiliary cancers.

Cancers of the esophagus and stomach

The global, randomized, double-blind, placebo-controlled RAINBOW trial provided evidence that adding ramucirumab to paclitaxel significantly improves overall survival (OS) for patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma who progressed on first-line platinum/ fluoropyrimidine-based combination therapy (Abstract LBA7). In the treatment group, OS improved from a median of 7.36 to 9.63 months (HR: 0.807; 95% CI [0.678-0.962]; p = 0.0169). RAINBOW now represents the second phase III trial of ramucirumab-based therapy for advanced gastric or GEJ cancer supporting use of the VEGFR-2 antagonist in the second-line setting.

In a presentation delivered during the General Session on Gastric Cancer— Etiology, Development, and Implications for Therapy, expert gastroenterologist David Y. Graham, MD, of Baylor College of Medicine, predicted that gastric cancer can be eliminated—within his lifetime—if the world works together to eradicate Helicobacter pylori. Several countries with high endemic rates of H. pylori, such as Japan, have already begun implementing a widespread twopronged plan of action, which includes primary prevention (H. pylori eradication) and secondary prevention (endoscopic surveillance of high-risk individuals)to eliminate gastric cancer.

Long-term follow-up of patients who underwent endoscopic resection of early gastric cancer indicate that posttreatment surveillance with CT scanning in combination with endoscopy is required for at least five years after lesion removal to detect recurrence (Abstract 2). These recommendations hold true regardless of whether patients meet the conventional criteria for endoscopic mucosal resection or expanded criteria for endoscopic submucosal dissection.

A prospective-retrospective study of superficial esophageal cancer showed that for patients undergoing endoscopic mucosal resection of esophageal intramucosal adenocarcinomas, the piecemeal and the en-bloc approach have similar results (Abstract 1). A comparison of the piecemeal and en-bloc techniques in 138 patients with 197 T1a lesions showed nearly identical complete remission rates (93.6% vs. 92.1%; p = 0.8), comparable local recurrence rates (6.4% vs. 7.9%; p = 0.7), equivalent OS (HR: 1.0; 95% CI [0.43-2.26]; p = 0.08), equivalent cancer-free survival (HR: 1.0; 95% CI [0.35-2.99]; p = 0.60), and similar incidences of complications (strictures: 2.4% vs. 1.5%, respectively; bleeding: 2.4% vs. 0%, respectively).

Cancers of the pancreas, small bowel, and hepatobiliary tract

The randomized, placebo-controlled, phase III EVOLVE-1 trial looked at 546 adult patients with advanced hepatocellular carcinoma who had progressive disease following sorafenib treatment. The study found that the mTOR inhibitor everolimus confers no survival benefit compared with placebo in the salvage setting (Abstract 172). The median OS was comparable for the two arms of the experiment, with 7.6 months for everolimus and 7.3 months for the placebo (HR: 1.05; 95% CI [0.86-1.27]; p = 0.675). The median time to progression also proved similar between arms, at 3.0 months with everolimus and 2.6 months with placebo (HR: 0.93; 95% CI [0.75-1.15]).

A phase II trial found a benefit to adding irinotecan drug-eluting beads (DEBIRI) to first-line treatment with FOLFOX in unresectable colorectal liver- limited metastatic cancer. The addition of DEBIRI enabled downstaging and subsequent resection in more than one-third of patients (Abstract 174). Findings showed that significantly more patients receiving DEBIRI attained a response to treatment compared with the control arm at two months (79% vs. 54%, respectively; p = 0.01), four months (91% vs. 59%, respectively; p = 0.03), and six months (83% vs. 64%, respectively; p = 0.05). Thereafter, 14 of the patients treated with DEBIRI went on to resection, as compared with five patients in the control arm (35% vs. 16%; p = 0.05). Importantly, placement of the beads in the hepatic artery did not increase chemotherapy toxicity or compromise overall treatment delivery.

Cancers of the colon and rectum

For patients with metastatic colorectal cancer (mCRC), extensive genetic testing for RAS gene mutations beyond routine analysis of KRAS exon 2 may soon become a new standard of care to pinpoint which patients stand to benefit from anti-EGFR therapy. That's according to a retrospective study that found that although activating mutations in KRAS exon 2—present in approximately 40% to 50% of mCRC tumors—are known to blunt the response to EGFR-targeted agents in mCRC, new data point to a longer list of problematic mutations within the RAS gene family. Activating mutations in exons 2, 3, and 4 of both KRAS and NRAS all predict a lack of response to panitumumab in the second-line setting based on a reanalysis of the randomized phase III 20050181 trial (Abstract LBA387). This finding corroborates results from the PRIME and PEAK trials regarding panitumumab efficacy in the first-line setting. Similar results for cetuximab in the first-line setting were also reported at other sessions at theSymposium.

Researchers from the National Surgical Adjuvant Breast and Bowel Project Biostatistical Center have developed the neoadjuvant rectal cancer score (NAR) that they believe could serve as a potential surrogate endpoint for early-phase clinical trials of neoadjuvant therapy (Abstract 384). In an analysis of data from the phase III neoadjuvant R-04 trial, the NAR score proved better at predicting OS than pathologic complete response, which is a surrogate endpoint in phase II neoadjuvant clinical trials of rectal cancer.

Final results from the phase III CAIRO3 trial provide guidance to clinicians uncertain about just how long a treatment holiday to give to their patients with mCRC following bevacizumab- containing induction therapy. The study compared maintenance therapy with capecitabine/bevacizumab versus observation after six cycles of first-line capecitabine/oxaliplatin plus bevacizumab. The maintenance approach markedly improved progression- free survival (Abstract LBA388). Moreover, multivariate analysis found that maintenance therapy independently improved OS in two groups of patients: those with synchronous disease who underwent resection of the primary tumor (median OS: 25.0 vs. 18.0 months; log-rank p value < 0.0001) and those who attained a complete or partial response to induction therapy prior to randomization (median OS: 24.1 vs. 18.8 months; log-rank pvalue < 0.0001).


To access complete Gastrointestinal Cancers Symposium Daily News coverage, visit gicasym.asco.org/dn.


Back to Top