This year’s ASCO saw a number of significant trials that were either practice-changing or had major effects on the field of treatment of non-colorectal gastrointestinal cancers. The ToGA trial found that for patients with HER2-positive gastric or gastroesophageal (GE) junction adenocarcinomas the addition of trastuzumab to chemotherapy resulted in a significant improvement in overall survival from 11.1 months to 13.8 months. Response rate and progression-free survival were likewise improved (47% vs. 35% and 6.7 mo vs. 5.5 mo, respectively). Approximately 22% of patients have tumors that are HER2 positive. It is recommended that patients with gastric or GE junction adenocarcinomas have their tumors tested by IHC or FISH for HER2 status; for those who are HER2 positive, trastuzumab should be considered. The LOGiC trial, which is looking at chemotherapy for HER2 patients with and without lapatinib, continues to accrue and we eagerly await the results of this trial. Other targeted agents currently undergoing trial in gastroesophageal cancers include bevacizumab and cetuximab. Both targeted agents have shown promising phase II data with improvements in overall survival compared to historical figures. We await data from a randomized phase III trial (AVAGAST) looking at chemotherapy with and without bevacizumab for patients with metastatic gastric cancer, and a randomized phase II trial of multiple chemotherapy regimens with cetuximab (CALGB 80403) for patients with metastatic esophageal cancer. Disappointing results of the promising drug S-1 were seen. S-1, an oral fluoropyrimidine with data suggesting possible superiority over 5-FU, was tested in a worldwide randomized controlled trial of S-1 plus cisplatin versus 5-FU plus cisplatin. Unfortunately, there was no survival difference seen between the two arms. It is still unclear if the negative results of this trial may have been due to a difference in dosing of cisplatin between the two arms or an issue with S-1 metabolism, which seems to differ between Eastern and Western patients.

For patients with localized esophageal cancers, data were shown using oxaliplatin as a component of the chemotherapy given with radiation therapy preoperatively. The SWOG S0356 trial was a phase II trial and showed a pathologic complete response rate for this treatment of 33%, compared to historical figures of other multicenter trials in the 15-20% range. This regimen will likely be taken forward into development as a chemotherapy backbone in future chemoradiation trials for patients with esophageal cancers. Preliminary toxicity data were also presented from the ARTIST trial, a phase III trial comparing adjuvant chemoradiation versus chemotherapy after D2 resection of gastric cancer. We await the efficacy results of this trial in helping direct the adjuvant treatment of gastric cancer, as we have now seen both studies that show benefit to chemoradiation therapy and perioperative chemotherapy alone.

The results of the first randomized phase III trial for patients with metastatic cholangiocarcinoma were also presented at ASCO this year. The ABC trial compared first-line chemotherapy with gemcitabine plus cisplatin versus gemcitabine alone, finding a statistically significant improvement in overall survival (11.7 mo vs. 8.2 mo) and progression-free survival (8.5 mo vs. 6.5 mo) with the combination therapy. The results of this trial contrast with negative phase III results that have been seen in pancreatic cancer trials testing gemcitabine plus platinum regimens, also showing that though we have treated cholangiocarcinomas like pancreatic cancers, they are two separate diseases. Gemcitabine plus platinum combinations should be seen as a standard of care chemotherapy treatment for cholangiocarcinomas and are being used as chemotherapy backbones in upcoming trials. The BINGO trial is randomizing patients with cholangiocarcinoma to gemcitabine and oxaliplatin plus or minus cetuximab. Preliminary results from this randomized phase II trial show a superior 4 month progression-free survival with the addition of cetuximab.

Data were shown looking at individualizing therapy for patients with pancreatic cancer. Nab-paclitaxel is an albumin-bound nanoparticle paclitaxel. It is thought that nab-paclitaxel will have increased accumulation in pancreatic cancer cells which overexpress SPARC via albumin binding to SPARC. A phase I trial of gemcitabine plus nab-paclitaxel showed an overall response rate of 26%. Twenty-nine percent of the tumors overexpressed SPARC, and showed a response rate of 75%. Progression-free survival was also improved in SPARC + patients (6.2 mo vs. 4.8 mo). These data are from small numbers of patients, but a phase III trial is planned. A phase II study of liposomal paclitaxel plus gemcitabine showed a median overall survival of 8.4-9.4 months, depending on the paclitaxel dose, compared with 7.2 months for gemcitabine alone. Though interesting phase II data, it is unclear if this survival improvement would hold true in a randomized phase III setting.

New results from a randomized study of octreotide LAR for patients with well-differentiated midgut neuroendocrine cancers showed an improvement in time to tumor progression (15.6 mo vs. 5.9 mo) with the use of octreotide LAR compared to best supportive care. There was some imbalance between the treatment arms on this study and no survival benefit was seen, though the study was not powered to look at survival.
Octreotide LAR has previously been indicated for control of side effects of secretory neuroendocrine cancers, but this trial suggests an antitumor benefit for well-differentiated neuroendocrine tumors in general.

We have made some progress from the results at this year’s ASCO towards improving survival for patients with non-colorectal gastrointestinal tumors, as well as advances in tailoring therapy to the patients and their specific tumors. Specifically, the major results include the use of trastuzumab for HER2-expressing gastric cancers, the now-proven standard of gemcitabine plus platinum for the treatment of cholangiocarcinomas, and the use of octreotide LAR to prolong time to tumor progression for neuroendocrine cancers. We await future data on the use of SPARC to guide the use of nab-paclitaxel for pancreatic cancers, and results on combinations of targeted agents with chemotherapy in esophagogastric and cholangiocarcinomas.