Eileen M. O’Reilly, MD, discusses the randomized phase II trial of gemcitabine and cisplatin versus gemcitabine and cisplatin and veliparib (ABT-888) in patients with pancreas adenocarcinoma (PDAC) harboring a known germline 

 mutation, which was presented at the 2020 Gastrointestinal Cancers Symposium. 

Both study arms were initially considered to be experimental arms, says O'Reilly. The investigators observed a very high response in both groups. The response rates in the triplet arm were higher than in the doublet arm, but the difference was not statistically significant. The progression-free survival was 10 months in both arms and there was also a signal of an overall survival benefit across arms, which was 15 months and 16 months, respectively.

In a pooled analysis that included all patients in the study, one-third lived 2 years following treatment and 20% lived 3 years. These data suggest that there is a tail on the curve for this subset of patient with pancreatic cancer. 

 View more from 2020 Gastrointestinal Cancers Symposium

Videos

Eileen M. O’Reilly, MD, discusses the randomized phase II trial of gemcitabine and cisplatin versus gemcitabine and cisplatin and veliparib in patients with pancreas adenocarcinoma harboring a known germline BRCA or PALB2 mutation, which was presented at the 2020 Gastrointestinal Cancers Symposium. 

Dr. O'Reilly on Veliparib/Chemotherapy Triplet in Germline BRCA/PALB2+ Pancreatic Cancer

Eileen M. O’Reilly, MD, associate director for Clinical Research, David M. Rubenstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center, discusses resistance to immunotherapy in patients with pancreatic cancer.

According to O’Reilly, many in the field consider pancreatic cancer to be an “immune-privileged” tumor. The effector T cells are typically either absent or present in very low levels in the tumor microenvironment. The immune cells that are present are, instead, regulatory or suppressive.

The goal, says O’Reilly, is to try and alter the tumor microenvironment to allow effector T cells in and to allow immunotherapy drugs in, in order to overcome some of the inherent resistance that has been regularly observed. There are some strategies out there that combine single-agent checkpoints, though they have limited impact. Some research has also looked at combining checkpoint drugs with antibodies that alter the microenvironment.

There are still several ongoing trials looking at the efficacy of various immunotherapy agents to treat patients with pancreatic cancer. A phase I/II open-label study is currently investigating the safety and efficacy of nivolumab (Opdivo) as a single agent and in combination with ipilimumab (Yervoy) in several different tumor types, one of which is pancreatic adenocarcinoma. Another trial is studying the side effects and best dose of ipilimumab when given together with gemcitabine hydrochloride in treating patients with stage III/IV or recurrent pancreatic cancer that cannot be removed by surgery. Both ipilimumab and gemcitabine hydrochloride can work in their own respective ways to either block or kill tumor cells. Thus, the idea of combining the 2 is to see if, together, they can kill more tumor cells more effectively.

Dr. O'Reilly on Resistance to Immunotherapy in Pancreatic Cancer

Eileen M. O’Reilly, MD, associate director for Clinical Research, David M. Rubenstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center, discusses factors that patients and oncologists should consider when developing a treatment plan for pancreatic cancer.

Oncologists will often take into consideration patients’ preference with factors such ability to come in often for infusions, fear of alopecia, and costs of care, which is becoming increasingly prevalent in the conversation regarding treatment planning, O’Reilly says.

Comorbidities and performance status are also considered, and as more therapies for pancreatic become available, more oncologists are questioning whether second-line therapies should be considered when choosing the initial treatment.

View more from the 2016 World Congress on GI Cancer

Dr. Eileen O'Reilly on Factors to Consider in Pancreatic Cancer Treatment

Eileen M. O’Reilly, MD, associate director, David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, discusses nab-paclitaxel plus gemcitabine versus FOLFIRINOX as frontline treatment for patients with metastatic pancreatic cancer.

O’Reilly says the decision to use one treatment over the other is a topic of hot debate. It is important to keep in mind that clinical trials evaluating nab-paclitaxel plus gemcitabine and FOLFIRINOX were done on different patient populations. Examining the bottom line of the two studies, it appears that FOLFIRINOX has the edge, in terms of efficacy. However, performance status and age have a big impact on outcomes, making cross comparison biased, notes O'Reilly.

Even though this issue is an important question to answer, O’Reilly feels that it might not warrant the resources required for a clinical trial, since both treatments are beneficial and provide further options for patients with pancreatic cancer.

View more from the 2014 World GI Congress

Eileen M. O'Reilly, MD, associate director, David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, discusses using nab-paclitaxel plus gemcitabine versus FOLFIRINOX as treatment for patients with untreated metastatic pancreatic cancer.

Eileen M. O'Reilly, MD

Articles

Dr. O'Reilly on Veliparib/Chemotherapy Triplet in Germline BRCA/PALB2+ Pancreatic Cancer

Dr. O'Reilly on Resistance to Immunotherapy in Pancreatic Cancer

Dr. Eileen O'Reilly on Factors to Consider in Pancreatic Cancer Treatment

Dr. O'Reilly on Nab-Paclitaxel Plus Gemcitabine Versus FOLFIRINOX in Pancreatic Cancer