2016 Gastrointestinal Cancers Symposium Provides Insight on Novel Mechanisms and Precision Care

Apr 28, 2016

Nearly 3,400 health care professionals gathered in San Francisco in January for the 2016 Gastrointestinal (GI) Cancers Symposium. Attendees, who included gastroenterologists, oncologists, surgeons, radiation oncologists, pathologists, patient advocates, and other members of the cancer care community, learned about state-of-the-art advances in the prevention and management of GI cancers and participated in interactive multidisciplinary sessions focused on a wide breadth of topics.

The research, carefully selected from 879 abstracts submitted by researchers from around the world, was presented in a variety of learning formats, including nine General Sessions, three Oral Abstract Sessions, three Keynote Sessions, and three Poster Sessions. As always, the Symposium offered numerous networking opportunities, including a Fellows, Residents, and Junior Faculty Networking Luncheon. New in 2016, five Breakout Sessions allowed for in-depth, targeted discussions on topics such as physician aid in dying and microsatellite instability tumors.

Cancers Of The Esophagus and Stomach

Results from a small randomized, phase II study conducted by the Chinese Western Cooperative Gastrointestinal Oncology Group in patients with locally advanced gastric adenocarcinoma suggest that a treatment sequence of mFOLFOX7 followed by mFOLFIRI in the first- and second-line settings, respectively, may prolong median overall survival (OS), compared with the reverse order (Abstract 1). Among the subgroup of 30 patients who completed both lines of therapy per protocol, median OS reached 20.2 months for the mFOLFOX7/mFOLFIRI group compared with 11.0 months for the mFOLFIRI/mFOLFOX7 group (p = 0.030). Total median progression-free survival (PFS) across both lines of therapy also favored mFOLFOX7/mFOLFIRI over mFOLFIRI/mFOLFOX7 (12.2 vs. 8.1 months, respectively; p = 0.008).

The GATSBY study, a multicenter, randomized, open-label, phase II/ III study conducted in 415 patients with previously treated HER2-positive locally advanced or metastatic gastric/ gastroesophageal junction adenocarcinoma, failed to show an efficacy benefit with trastuzumab emtansine (T-DM1) over taxane chemotherapy (Abstract 5). Median OS, the primary endpoint, reached 7.9 months with once-weekly T-DM1, compared with 8.6 months with taxane chemotherapy (HR 1.15, 95% CI [0.87, 1.51]; p = 0.8589). T-DM1 did show a numerical advantage compared with taxane chemotherapy, represented by a lower incidence of grade 3 or higher adverse events (59.8% vs. 70.3%).

Initial data from the phase I/II Check- Mate-032 study of nivolumab suggest that the anti-PD-1 antibody is both active and well tolerated when given as monotherapy to patients with advanced and metastatic gastric or gastroesophageal junction cancer (Abstract 6). The confirmed objective response rate (ORR) among 59 heavily pretreated patients with unselected PD-L1 tumors reached 14%. When broken down by PD-L1 status, ORRs were 27% and 12% for patients with PDL1- positive and PD-L1-negative tumors. Notably, 36% of patients remained alive at the 12-month mark, which compares favorably with typical 1-year OS rates of 20% for patients receiving chemotherapy in the second- and third-line settings.

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Impressive results from the large phase III NETTER-1 trial comparing 177Lu- DOTATATE with high-dose octreotide LAR in patients with advanced midgut neuroendocrine tumors that progressed following first-line somatostatin analog therapy position the investigational agent as a viable second-line treatment option if approved by regulatory agencies (Abstract 194). The study results demonstrated a clinically meaningful and statistically significant 79% reduction in the risk of PFS. 177Lu- DOTATATE also trumped octreotide LAR with regard to ORR (18% vs. 3%; p = 0.0008) and showed promise of an OS improvement at the interim analysis (13 vs. 22 deaths; threshold for statistical significance at interim analysis [p = 0.001] not met).

Noncolorectal GI cancers with mismatch repair (MMR) deficiency appear to be highly responsive to anti-PD-1 checkpoint blockade, according to results from a small phase II study (Abstract 195). Among 17 patients with previously treated, progressive, advanced noncolorectal GI cancers with MMR deficiency, treatment with pembrolizumab yielded an ORR of 47% and a disease control rate of 76%. Moreover, responses were seen across all types of tumors—pancreas, ampullary, biliary, gastric, and small bowel. Median PFS is not yet estimable; median OS is 21 months.

The international, randomized, doubleblind, placebo-controlled phase III MAESTRO trial of evofosfamide, a hypoxia-activated prodrug, failed to meet the primary OS endpoint when combined with gemcitabine, compared with gemcitabine alone, in unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma (Abstract 193). Median OS was statistically similar between the evofosfamide/gemcitabine and placebo/gemcitabine arms at 8.7 months and 7.6 months (HR 0.84, 95% CI [0.71, 1.01]; p = 0.0589), respectively, narrowly missing the mark for significance. Two potential factors that might explain the disappointing OS findings are better-than-expected survival in the control arm and a higher frequency of second-line therapy in the control arm.

Cancers of the Colon, Rectum, and Anus

A commercial blood-based immunoassay that assesses serum levels of four biomarkers—carcinoembryonic antigen, high-sensitivity C-reactive protein, ferritin, and cytokeratin fragment 21-1—offers potential for identifying colorectal neoplasia in early stages, thereby improving patients’ chances of avoiding or surviving malignant disease (Abstract 488). At 90% sensitivity, the four-biomarker model showed a 25% positive predictive value and a 93% negative predictive value for discriminating individuals known to have colorectal cancer or high-risk adenoma. Additional markers are being evaluated to enhance the accuracy of the tool.

A retrospective study (Abstract 491) of more than 29,000 individuals within the Netherlands Cancer Registry who were diagnosed with rectal cancer from 1989 to 2007 found that those who received radiotherapy had a marginally increased risk of developing another primary tumor later in life compared with the general population (23.3 of 10,000 excess cases per year). However, radiotherapy appeared to confer a protective effect against the development of secondary tumors compared with patients who did not receive radiotherapy (HR 0.70, 95% CI [0.61, 0.81]), predominantly for secondary prostate cancers (HR 0.51, 95% CI [0.43, 0.62]).

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