ASCO Highlights for Tuesday June 5, 2018

By Lynne Lederman, PhD

On this final day of the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting we look at two late breaking presentations. LBA 4008, presented late yesterday, showed proton pump inhibitors with low dose aspirin for at least 7 years offers modest benefits for people with Barrett’s esophagus, a risk factor for the development of adenocarcinoma of the esophagus. And, LBA 3505, presented today showed no benefit for using hyperthermic intraperitoneal chemotherapy (HIPEC) during surgery to treat most patients with colorectal cancer with colorectal peritoneal carcinomatosis, suggesting that those patients with CRC that has spread only to the peritoneum can avoid HIPEC treatment.

Chemoprevention of esophageal cancer with esomeprazole and aspirin therapy: efficacy and safety in the phase 3 randomized factorial ASPECT trial (LBA4008)

Janusz Jankowski, MD, Royal College of Surgeons, Ireland, presented an updated analysis of the ASPECT trial. The analysis showed that the risk of developing precancerous, high grade dysplasia or esophageal cancer could be reduced, and that the risk of death from any cause was delayed in individuals with Barrett’s esophagus (BE) with the use of the proton pump inhibitor (PPI) and low dose aspirin. This 7-year study is important because esophageal cancer, which is associated with BE is difficult to screen and treat, and the drugs used in the study, esomeprazole (a PPI) and aspirin, are dosed orally and available over the counter. Dr. Jankowski cautioned that people with heartburn should discuss their risk of BE with their health care provider and should not self-medicate with the study drugs.

Esophageal adenocarcinoma has a 5-year survival rate of less than 10%, and is increasing in incidence, probably due to an increase in gastro-esophageal reflux and BE, which are both associated with inflammation. PPIs reduce acid reflux, and aspirin reduces inflammation, so both agents can be preventative.

This study enrolled 2,563 patients with ≥1 cm BE and no high grade dysplasia or esophageal adenocarcinoma at baseline. Patients were randomly assigned 1:1:1:1 in a 2 x 2 factorial design to high or low dose esomeprazole alone or in combination with low dose aspirin. The primary composite endpoint was time to all-cause mortality, esophageal adenocarcinoma, or high grade dysplasia.

Median follow-up was 8.9 years. High dose esomeprazole had a statistically significant benefit on the combined endpoint compared with standard dose esomeprazole (P=.0459). Aspirin had no benefit in the no-aspirin arm in the primary analysis. Dr. Jankowski said it was stunning that the serious adverse event rate was low, about 1%.

In discussing this trial, Zev Wainberg, MD, David Geffen School of Medicine, UCLA, pointed out that despite the absolute benefits of high dose PPI and use of aspirin, there are many unanswered questions. Until there are more data, the question of whether all patients with BE should receive treatment with high dose PPI plus low dose aspirin can’t be answered.

A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7 (LBA3505)

This randomized, phase 3 trial (NCT00769405) showed that individuals with advanced colorectal cancer (CRC) may not require treatment with hyperthermic (heated) intraperitoneal chemotherapy (HIPEC) during surgery. HIPEC does not offer a survival advantage compared with surgery alone. The study results were presented by François Quenet, MD, Institut Régional du Cancer de Montpellier, Montpellier, France.

Patients with peritoneal CRC metastases are known to have a significantly worse prognosis than those with no peritoneal metastases.

Prodige 7 was a phase 3 trial in patients with peritoneal carcinomatosis of CRC origin who underwent complete surgical resection to ≤1 mm, then were randomly assigned to HIPEC (n=133) or no HIPEC (n=132), followed by systemic chemotherapy per physician choice for 6 months which could be administered pre-operatively, post-operatively, or both. Patients who had a peritoneal cancer index (PCI) of <25 were eligible for enrollment. PCI is prognostic for survival. Patents in the study had a median PCI of 10.

At a median follow-up of 64 months, the median overall survival (OS) was not statistically significantly different between groups at 41.2 months in the non-HIPEC group and 41.7 months in the HIPEC group. Median recurrence-free survival was also similar between the two groups at 11.1 months in the non-HIPEC group and 13.1 months in the HIPEC group. In a subgroup analysis, as expected, patients with lower PCI scores had longer OS. For patients with a PCI score of 11 to 15, there was a significant survival advantage for patients who received HIPEC versus none. However, there were only 18 (13.5%) such patients in the HIPEC group and 28 (21.2%) in the non-HIPEC group.

The overall mortality rate at 30 days after surgery was 1.5% in both groups, and adverse events were comparable between groups at this time point. At 60 days, the total mortality rate was 2.6%. At 60 days, the  rate of adverse events in the HIPEC group was significantly higher than that in the non-HIPEC group (24.1% versus 13.6%; P=.03). Hospital stays for the HIPEC group were also significantly longer.

Dr. Jankowski concluded that more research is needed to determine if there are patients with CRC metastases confined to the peritoneum who would still benefit from receiving HIPEC with surgery. Patients with a low PCI are not likely to benefit from HIPEC. The curative management of peritoneal carcinomatosis by cytoreductive surgery in this study yielded unexpectedly good OS results.

People with CRC metastases confined to the peritoneum with a low peritoneal cancer index can likely forgo HIPEC, whereas those with a high index may not benefit from either surgery or HIPEC. Meanwhile, other types of chemotherapy may be more effective than oxaliplatin, the type of chemotherapy used in HIPEC for this study.

In discussing this study, Larissa Temple MD Rochester Medical Center, said that it is too early to tell if this study will be practice changing, in part because of the relatively low median PCI score. A very high resection rate in this study likely contributed to a 30 and 60 day mortality lower than in retrospective data. Other ongoing randomized, controlled trials should provide more information as role of HIPEC treatment for CRC metastases confined to the peritoneum evolves.

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