Apr 17, 2013
The 2013 Gastrointestinal Cancers Symposium was held January 24-26, in San Francisco, California. The following highlights are courtesy of the Gastrointestinal Cancers Symposium Daily News team.
The 2013 Gastrointestinal (GI) Cancers Symposium marked the 10-year anniversary of this annual meeting. In the last 10 years, nearly 24,000 people from 109 countries have attended the Symposium, and 2013 saw an additional estimated 2,775 clinicians added to that number. In addition, much progress has been made in research for GI cancers, as evidenced in the three Decade in Review sessions each addressing colorectal, esophagus and stomach, and pancreatic and hepatobiliary cancers.
Daniel D. Von Hoff, MD, discusses the report of the randomized phase III MPACT trial during the 2013 Gastrointestinal Cancers Symposium.
Cancers of the esophagus and stomach
The randomized, open-label, controlled, phase III COUGAR-02 trial conducted in the United Kingdom provided definitive evidence that administering docetaxel in tandem with best supportive care(BSC) prolongs overall survival, improves pain scores, and maintains global quality of life in a Western population of patients with relapsed esophagogastric adenocarcinoma (Abstract LBA4). Overall survival increased from 3.6 months with BSC alone to 5.2 months with the addition of docetaxel, translating into a 33% reduction in the risk of death (hazard ratio [HR]: 0.67; p = 0.01). Importantly, treatment with docetaxel not only helped patients live longer, but it also helped them feel better and did not adversely affect patient functioning.
The very large, global, randomized, double-blind, placebo-controlled REGARD trial supported treatment of relapsed esophagogastric cancer with ramucirumab (Abstract LBA5). The addition of this novel monoclonal antibody targeting vascular endothelial grown factor receptor-2 (VEGFR-2) to BSC in the second-line setting significantly prolonged median overall survival—the primary endpoint—from 3.8 to 5.2 months, translating into a 22% reduction in the risk of death (HR: 0.78; p = 0.0473). Ramucirumab also significantly prolonged median progression-free survival from 1.3 months to 2.1 months when added to BSC (HR: 0.483; p < 0.0001) and more than doubled the disease control rate compared with BSC alone (48.7% vs. 23.1%; p < 0.0001).
Other noteworthy research:
- TyTAN (phase III): indicated that HER2-targeted therapy has the potential to prolong patient survival when used in the second-line setting in HER2-positive advanced gastric cancer, but only in individuals who test HER2 positive by immunohistochemistry (IHC 3+; Abstract 11). The findings of a preplanned subgroup analysis revealed that median overall survival in the HER2 IHC 3+ subgroup improved from 7.6 months to 14.0 months with the addition of lapatinib to paclitaxel—a striking and significant 6.4-month difference (HR: 0.59; p = 0.0176).
- SCOPE 1 (phase II/III): showed that cetuximab plus chemoradiotherapy failed to improve survival in an unselected population of patients with esophageal cancer (Abstract LBA3). In fact, all survival outcomes were consistently better when cetuximab was omitted rather than included with chemoradiotherapy.
- The largest study conducted to date comparing HER2 testing methods in esophageal adenocarcinoma indicates that IHC is the preferred initial screening method, with fluorescent in situ hybridization (FISH) referral needed only when the IHC results are indeterminate (i.e., IHC 2+) (Abstract 2).
- A controlled study of patients with metastatic or recurrent gastrointestinal stromal tumors (GIST) identified improved survival outcomes with surgical resection of residual lesions after disease control with imatinib (Abstract 62).
Cancers of the pancreas, small bowel, and hepatobiliary tract
The most exciting findings of the meeting came from the report of the randomized phase III MPACT trial presented by lead investigator Daniel D. Von Hoff, MD, of the Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen (Abstract LBA148). This large, global study performed at 151 community and academic centers demonstrated that the addition of nab-paclitaxel to gemcitabine in patients with metastatic pancreatic cancer yielded statistically significant and clinically meaningful improvements in all endpoints across all subgroups compared with gemcitabine alone.
The improvement in overall survival—the primary endpoint—was the real triumph of the trial:
- Median overall survival was 8.5 months nab-paclitaxel plus gemcitabine versus 6.7 months with gemcitabine alone (HR: 0.72; p = 0.000015).
- At 12 months, the survival rate was 35% with the combination versus 22% with gemcitabine alone, translating into a 59% increase in survival (p = 0.00020).
- Moreover, survival at two years doubled with the addition of nab-paclitaxel to gemcitabine, increasing from 4% to 9% (p = 0.02123).
The overall survival benefit associated with the two-drug combination persisted across all prespecified patient subgroups.
JASPAC-01 found that adjuvant chemotherapy with the oral fluoropyrimidine S-1 clearly beat out gemcitabine for several efficacy and safety endpoints at the time of the interim data analysis (Abstract 145). Although the trial was originally designed as a noninferiority study, two-year overall survival was 70% with S-1 compared with 53% with gemcitabine (HR: 0.56; 99.8% confidence interval: 0.36-0.87), thus not only establishing S-1 noninferiority (p < 0.0001) but also its superiority (p < 0.0001, log-rank test) in comparisonwith gemcitabine—heretofore considered the standard treatment for resected pancreatic cancer in Japan.
Additional key findings included research on the SCALOP (phase II) study (Abstract 146); gene expression profiling of circulating pancreatic cancer cells (Abstract 142); and therapeutic targeting of the IL-17A signaling axis for early pancreatic cancer (Abstract 144).
Cancers of the colon and rectum
Italian investigators led by Fotios Loupakis, MD, PhD, of the Istituto Toscano Tumori in Livorno, Italy, have now confirmed through the randomized phase III TRIBE trial that the FOLFOXFIRI triplet remains superior to the FOLFIRI doublet for first-line treatment of metastatic colorectal cancer (mCRC), even when bevacizumab is added to both arms (Abstract 336). The primary endpoint of median progression-free survival topped out at 9.7 months with FOLFIRI and bevacizumab compared with 12.2 months with FOLFOXFIRI and bevacizumab (HR: 0.73; p = 0.0012). Likewise, the doublet yielded an overall response rate of 53% whereas the triplet boosted the rate to 65% when each was paired with bevacizumab (p = 0.006).
FOLFOXFIRI and FOLFIRI matched up well regarding overall safety, although the incidence of diarrhea (19% vs. 11%), stomatitis (9% vs. 4%), and neutropenia (50% vs. 20%) did increase with the triplet as compared with the doublet. Data are still being collected to determine longer-term outcomes such as overall survival.
Additional key findings included research on the addition of bevacizumab to capecitabine in patients 70 years and older (Abstract 337); CONTRE (phase II), suggesting that complete neoadjuvant treatment can be safely administered to patients with CRC (Abstract 335); and analysis of data from a population-based cohort that revealed that adjuvant chemotherapy does confer a survival advantage in high-risk patients with stage II CRC (Abstract 338).
Access complete Gastrointestinal Cancers Symposium Daily News coverage online.