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Eng Expands on Evolving GI Cancer Landscape

Brandon Scalea
Published: Thursday, Aug 09, 2018

Cathy Eng, MD
Cathy Eng, MD
Recent clinical findings across gastrointestinal (GI) cancers addressed unanswered questions in a number of patient populations, said Cathy Eng, MD.

For example, preliminary results of the PRODIGE 24/CCTG PA.6 trial, which were presented at the 2018 ASCO Annual Meeting, demonstrated a significant improvement in overall survival (OS) for patients with resected pancreatic cancer who received adjuvant therapy with a modified FOLFIRINOX regimen (mFOLFIRINOX) versus gemcitabine. Data showed that mFOLFIRINOX induced a 36% reduction in the risk of death versus gemcitabine (HR, 0.64; 95% CI, 0.48-0.86; P = .003). The median OS was 54.4 months with the 4-drug regimen versus 35.0 months with gemcitabine.

Moreover, the PRODIGE 7 trial gave the community insight on the role of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis. Data showed that HIPEC added to surgery did not result in a statistically significant improvement in OS. Eng added that this patient population, which generally has a bleak prognosis, needs to be further addressed.

Furthermore, the ADORE trial provided data in the locally advanced rectal cancer setting. The study tested the addition of adjuvant oxaliplatin to leucovorin and 5-fluorouracil (5-FU; FOLFOX) versus leucovorin/5-FU alone. The primary endpoint of disease-free survival suggested a clear benefit with the addition of oxaliplatin.

In an interview with OncLive, Eng, professor of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, highlighted recent data that could shape the treatment landscape for several GI cancers.

OncLive: Please discuss the impact of the PRODIGE 24 study.

Eng: It was a dramatic, dramatic increase in OS. It's important for the community to know this because gemcitabine has been the standard of care for years. The reality is if the patient can tolerate mFOLFIRINOX, and if you watch the patients closely, it really works. That's truly groundbreaking.

What are some unanswered questions that remain for this study?

This was a well-designed study from what I gathered. Honestly, there was a significant improvement in OS for this patient population that has very few options and usually does very poorly in general. This is a fantastic step forward. Importantly, it doesn't involve immunotherapy. It involves drugs that are currently being utilized, so it can be implemented very soon.

What are your thoughts on PRODIGE 7?

PRODIGE 7 is looking at HIPEC in patients with peritoneal carcinomatosis. They had a really good median follow-up with the less than 300 enrolled patients. This was [from] a terrific institution with great researchers. They did not notice any difference in OS with the use of HIPEC in this patient population. The small little nuances of this study are really important; there hasn't been a trial of this setting in over 15 years.

This is a huge problem for patients with this disease. These patients have very poor quality of life, especially if there's peritoneal disease and bowel obstruction. We need new advances. Although this trial was negative, it does highlight that there is the need to move forward in the sense we need to look more at Peritoneal Cancer Index scores. We also need to keep getting people interested; we don't need to wait another 15 years. Therefore, while the trial was negative, it provided valuable information.

Can you expand more on this patient population?

These patients have peritoneal carcinomatosis. Basically, these patients have small tumors throughout their abdominal cavity. It's not in one specific organ, which makes it very challenging. That is why when they're not treated properly or if they're refractory, they end up with bowel obstruction. We often give these patients chemotherapy; however, it is not addressing the issue well enough.

Can you share some insight on some of the rectal cancer studies presented at the 2018 ASCO Annual Meeting?

I was the discussant on 2 rectal studies that were updated¬—a German trial and a Chinese study. They were looking at the role of oxaliplatin as a radiation sensitizer. This was also addressing the adjuvant setting. Both of these phase III trials were negative, but it does emphasize that we shouldn't be using oxaliplatin for this purpose. What was unique about the Chinese study, though, was that the third arm gave chemotherapy only to patients with rectal carcinoma and omitted radiation therapy.

Are there any other trials you want to mention?

I do want to mention the ADORE trial. This was the study looking at the role of adjuvant chemotherapy based on your pathologic postoperative staging. Researchers noted and validated once again that there's an improvement in disease-free survival for a stage III patient utilizing FOLFOX. I wanted to mention this because it's a very controversial topic regarding the role of adjuvant chemotherapy in rectal cancer. Thus far, these are the best data we've seen.
Conroy T, Hammel P, Hebbar M, et al; CCTG and the UNICANCER-GI/PRODIDGE Group. Unicancer GI PRODIGE 24/CCTG PA.6 trial: a multicenter international randomized phase III trial of adjuvant mFOLFIRINOX versus gemcitabine (gem) in patients with resected pancreatic ductal adenocarcinomas. J Clin Oncol. 2018;36 (suppl; abstr LBA4001). meetinglibrary.asco.org/record/159164/abstract.




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