Expert Discusses Emerging Treatments in Early Pancreatic Cancer

Afsaneh Barzi, MD

Studies in the neoadjuvant and adjuvant settings of pancreatic cancer have brought excitement to this treatment paradigm. According to Afsaneh Barzi, MD, some of the most eagerly anticipated data in the field are from a combination study of adjuvant gemcitabine and nab-paclitaxel (Abraxane).

The randomized phase III APACT trial is exploring adjuvant treatment with nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with resected pancreatic cancer (NCT01964430).

This combination also has activity in the neoadjuvant setting, as demonstrated in the LAPACT trial, which showed a 78% and 33% disease control rate amd objective response rate, respectively, during induction. The median time to treatment failure was 8.8 months and the median progression-free survival was 10.8 months.

Additionally, the widespread implementation of genetic testing for patients and their families affected by pancreatic cancer is something Barzi said needs more attention. This could be the first step to disease prevention, she noted.

OncLive: What are the available and emerging neoadjuvant strategies?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Gastrointestinal Cancers, Barzi, assistant professor of clinical medicine, medical director, Keck School of Medicine of University of Southern California (USC), USC Norris Comprehensive Cancer Center, discussed updates in the treatment of patients with pancreatic cancer, as well as the importance of genetic testing.Barzi: For a while, the standard practice has been to start these patients on gemcitabine, and then look for response and resectability. However, the response rate to gemcitabine is so poor that very few of these patients ever get to surgery.

The LAPACT trial looked at the combination of gemcitabine and nab-paclitaxel. In the initial trial, MPACT, gemcitabine plus nab-paclitaxel was only used in metastatic populations. Therefore, we did not have any data for the efficacy of this treatment in the locally advanced population. The LAPACT trial established that 36% of the patients responded to treatment, and about 15% of them actually went for surgery.

What are some of the important data from these pivotal trials?

There is also a meta-analysis of a few smaller FOLFIRINOX studies that have been done in the locally advanced population. Approximately 28% of those patients were able to go onto surgery. Those numbers are impressive, and what that tells us is that as our chemotherapies are getting better, we should be sure to reevaluate [our locally advanced patients] for resectability. As medical oncologists, we forget that when we give these patients stronger, more potent therapies, we are potentially rendering them resectable. Every single time there is a staging study, we should discuss points for resection with our surgeons. There may not be, but those few tumors that we can find and resect are worth the effort.ESPAC-4 established a combination of gemcitabine and capecitabine to be superior to gemcitabine alone. The study had 730 patients and showed an 18% improvement in overall survival (OS) with the combination. There are a few caveats to this study. It has a very high percentage of the R1 resection—about 60% of the study population had R1 resection, which is higher than any other adjuvant study that has been published. They looked at the R1 population, and there is absolutely no difference in survival when you look at gemcitabine alone versus gemcitabine plus capecitabine. That is an important that we should keep in mind.

FOLFIRINOX versus gemcitabine is another [neoadjuvant] study, but that paper is not published so the data are limited to the presentation. They looked at gemcitabine versus FOLFIRINOX in the adjuvant setting, and showed a much larger improvement in disease-free survival and OS compared with ESPAC-4. Therefore, in the very fit patient population, FOLFIRINOX is perhaps a better choice.

Are there any clinical trials of interest in this space?

There are some caveats to that. Everybody believes that FOLFIRINOX is extremely toxic. Toxicity is worth it, but it is a discussion we should have with our patients. Still, 33% of the patients will discontinue treatment due to toxicities. The reason I bring it up is because managing the toxicity with adequate supportive care is critical to maintaining the patients on treatment and hopefully have benefit.Results of the adjuvant gemcitabine and nab-paclitaxel study are anxiously awaited by pretty much everybody. There is another ongoing adjuvant study in Europe that is looking at the combination of gemcitabine plus cisplatin. Those results should come out sometime soon. We will have some additional data for the adjuvant setting, and perhaps more confusion.

Where is the field at currently regarding genetic testing?

In terms of personal interest, I am a strong believer of genetic evaluation—not just for the sake of patients, but it is our opportunity to prevent cancer in family members. This is something that we should think about not just for the sake of our patients, but for the sake of prevention.There is no standard practice for genetic testing in pancreatic cancer. Patients with pancreatic cancer should undergo genetic testing if they are diagnosed at a young age. We usually target those who are diagnosed under the age of 50, or if there is a serious and significant family history of the cancer that prompts the referral for genetic testing.

Have there been any updates in surgery to report?

For the population with metastatic disease, sometimes detection of molecular markers such as BRCA1/2 in their tissue prompts us to refer these patients for genetic testing to see if that the mutation is genomic versus somatic.As time passes, we get more and more aggressive with surgery. Some essential factors are that surgery for pancreatic cancer should absolutely only happen in high-volume centers. That is critical, and the expertise of the surgeon is important for outcomes of the disease in general.

In terms of the newer approaches, the pylorus-preserving Whipple procedure is relatively new compared with the old Whipple. More surgeons are doing the pylorus-preserving Whipple procedure in select patients, which has better outcomes when it comes to tolerability, eating, and less gastrointestinal symptoms after the procedure.

Our improvement with imaging techniques have actually changed how we choose our patients for surgery. Nowadays, surgeons are getting more aggressive with vascular repair, so that is kind of the trend. We do laparoscopic pancreatectomy, which is a little bit less invasive. And perhaps, we can get the patients out faster and get them on adjuvant therapy faster.

Hammel P, Lacy J, Portales F, Sobrero AF, Pazo Cid RA, Mozo JLM. Phase II LAPACT trial of nab-paclitaxel (nab-P) plus gemcitabine (G) for patients with locally advanced pancreatic cancer (LAPC). J Clin Oncol. 2018;36(4):204. doi: 10.1200/JCO.2018.36.4_suppl.204.