Apr 26, 2015
The 12th annual Gastrointestinal (GI) Cancers Symposium was held January 15-17, 2015, in San Francisco. More than 3,400 gastroenterologists, oncologists, surgeons, radiation oncologists, pathologists, and other members of the cancer care community gathered to exchange ideas, best practices, and scientific research. More than 50% of attendees at the Symposium hailed from outside of the United States, with representation from 70 different countries.
Reflecting the meeting’s theme of “Bridging Cancer Biology to Clinical GI Oncology,” this year’s sessions featured several timely studies pulled from the more than 830 abstracts submitted by researchers from around the globe.
Social media at the Symposium continued to play a large role in allowing attendees to share useful information with the public and to connect with one another and the larger cancer community. Using the hashtag #GI15, attendees at this year’s meeting sent out 1,889 tweets. The Symposium also offered multiple opportunities for in person networking through programs such as Poster Walks and eQ&A, which for the first time was featured at all general sessions.
The promise of immunotherapy
In a keynote lecture, Ronald Levy, MD, of the Division of Oncology at Stanford University, described recent breakthroughs in immunotherapy and how these might be applied to GI malignancies. As Dr. Levy explained, to fully harness the power of the body’s immune system to attack tumors and prevent tumors from evading such immune responses, research is being focused on regulating activation of the PD-1 immune checkpoint pathway. Anti–PD-1 and anti–PD-L1 monoclonal antibodies emerging from these efforts represent the newest frontier in immune-based cancer treatments.
“Probably the most important observation that came out of this meeting is that the companies and groups doing research with the new immune therapies— the checkpoint inhibitors—seem to have decided that, in fact, it may be reasonable to explore these agents in GI malignancies, which will give us some tools to work with in the upcoming months and years,” said Alan P. Venook, MD, of the University of California, San Francisco, a member of the GI Symposium faculty and Chair of the 2015 ASCO Annual Meeting Scientific Program Committee.
Following Dr. Levy’s lecture, Kei Muro, MD, of the Aichi Cancer Center Hospital in Japan, presented data on pembrolizumab activity and safety in patients with gastric cancer based on findings from the phase Ib KEYNOTE-012 trial (Abstract 3). Pembrolizumab is a humanized anti–PD-1 monoclonal antibody that was recently approved for use in metastatic melanoma but has been quickly gaining ground in other tumor types as well. Among 39 individuals with gastric cancer included in KEYNOTE-012, two-thirds of whom had received at least two prior therapies for advanced disease, 22.2% (95% CI [10, 39]) achieved an objective response (OR) (all partial responses [PR]) to pembrolizumab according to central review; according to investigator review, 33.3% achieved an OR (95% CI [19, 50]). Moreover, 53.1% of patients with measurable disease displayed some degree of tumor shrinkage from baseline.
Promising targeted therapies
A phase Ib study focused on PF-04136309—arguably an immunotherapy, given its mechanism of action as a chemokine receptor type 2 (CCR2) antagonist that functions by depleting inflammatory monocytes and tumorassociated macrophages that contribute to an immunosuppressive tumor microenvironment. Results of the study showed that nearly one-half of patients (48%) with borderline resectable or locally advanced pancreatic cancer achieved an OR with the addition of PF-04136309 to fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) chemotherapy, allowing the majority of these individuals to achieve R0 resection (Abstract 338). Among 29 patients, 14 had PRs, 14 had stable disease, and just one patient had progressive disease. The CCR2 agonist was also able to deplete inflammatory monocytes and repolarize the tumor microenvironment through upregulation of anti-tumor cytokines.
A phase I analysis of single-agent AMG 337, an investigational oral MET tyrosine- kinase inhibitor, found that among 13 individuals with MET-amplified gastroesophageal junction, gastric, or esophageal adenocarcinomas, eight patients—62%—achieved an OR in response to the drug (Abstract 1). One patient achieved a complete response with a duration currently extending to almost three years (155+ weeks), and the other seven patients attained a PR, with durations currently lasting from nine weeks to almost two years (96+ weeks).
Minimally invasive surgery for gastric and esophageal cancers
The MIRO trial, which enrolled 207 patients with resectable cancers of the middle or lower third of the esophagus, revealed a 69% decrease in the risk of 30-day, grade II to IV postoperative morbidity with laparoscopicassisted esophagectomy compared with the conventional approach (OR 0.31; 95% CI [0.18, 0.55]; p < 0.0001) (Abstract 5). In addition, at 30 days postsurgery, the incidence of major pulmonary complications—which typically account for 50% of all postoperative deaths—reached 30.1% in the control arm but only 17.7% in the laparoscopic arm (p = 0.37).
Christophe Mariette, MD, PhD, of the Claude Huriez University Hospital in Lille, France, first author of the study and presenter, said, “These findings provide strong evidence for the use of [hybrid minimally invasive esophagectomy] for patients with resectable esophageal cancer. We think that [hybrid minimally invasive esophagectomy] should be considered as a new standard for esophageal cancer surgery.”
Vitamin D in metastatic colorectal cancer
A study presented by Kimmie Ng, MD, MPH, of the Dana-Farber Cancer Institute, found that patients with metastatic colorectal cancer (mCRC) who had high levels of plasma vitamin D prior to first-line systemic therapy lived a median of 8.1 months longer than those with low vitamin D levels, according to a preplanned analysis of the phase III CALGB/SWOG 80405 trial (Abstract 507). After accounting for multiple variables, patients with the highest levels of vitamin D still showed a 35% improvement in the risk of mortality, as compared with individuals with the lowest levels (hazard ratio [HR] 0.65; 95% CI [0.51, 0.83]; p = 0.001).
Elevated baseline alpha-fetoprotein heralds ramucirumab OS benefit
Previous analysis of the randomized, double-blind, phase III REACH trial failed to demonstrate a significant survival benefit with second-line ramucirumab in patients with advanced hepatocellular carcinoma (HCC) following first-line treatment with sorafenib. However, more recent analyses of the REACH data, presented by Andrew X. Zhu, MD, PhD, of the Massachusetts General Hospital, indicate that elevated baseline levels of alpha-fetoprotein (AFP)—a factor long known to correlate with a poor HCC prognosis—may predict for extended survival with ramucirumab treatment (Abstract 232). Specifically, patients with an AFP level of 400 ng/mL or greater at baseline had a median OS of 7.8 months for those treated with ramucirumab, compared with 4.2 months among those who received placebo—a risk reduction of 33% (HR 0.674; 95% CI [0.508, 0.895]; p = 0.0059).
To access complete Gastrointestinal Cancers Symposium Daily News coverage, vist gicasym.asco.org/dn.