Personalized Therapy Becoming Reality in Pancreatic Cancer

Diana L. Hanna, MD

Multidrug regimens and precision-based therapies are creating a more optimistic future for patients with advanced pancreatic cancer; however, more data and improved clinical trial enrollment are needed to move the needle forward, said Diana L. Hanna, MD.

For example, an effective maintenance regimen is being explored for patients with metastatic disease, following data from the phase II PRODIGE-35/PANOPTIMOX trial that were presented at the 2018 ASCO Annual Meeting.

In the study, patients with metastatic pancreatic cancer were randomized to 3 treatment arms: arm A, FOLFIRINOX every 2 weeks for a maximum of 12 cycles; arm B, FOLFIRINOX during 4 months for 8 cycles, followed by LV5FU2 as maintenance therapy until progression; and arm C, alternating FOLFIRI.3 with gemcitabine every 2 months.

Data showed that arm B was comparable with arm A. The median OS in Arms A, B, and C were 10.1 months (95% CI, 8.5-12.2), 11.0 months (95% CI, 8.7-13.1), and 7.3 months (95% CI, 5.7-9.5), respectively.

Hanna, an assistant professor of clinical medicine at University of Southern California Keck School of Medicine, said there are multiple trials ongoing looking at combinations of immunotherapy, chemotherapy, and other agents in metastatic pancreatic cancer.

OncLive: How have therapies changed over the last several years for advanced pancreatic cancer?

What practice-changing studies have we learned about this year?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Gastrointestinal Cancers, Hanna discussed the past, present, and future of treatment for patients with metastatic pancreatic cancer.Hanna: About 20 years ago, we only had 1 drug: gemcitabine. Since then, we have evolved to multidrug regimens and precision-based therapies. We are even now talking about maintenance strategies, and all other things that seemed foreign and out of reach for us not too long ago. We are giving patients hope.There was a practice-changing trial related to how we sequence therapies. It looked at maintenance therapy, which has not been well-defined in this disease. It was a phase II study with 3 arms. It looked at traditional FOLFIRINOX until progression versus 4 months of treatment followed by maintenance compared with alternating gemcitabine and FOLFIRINOX. The maintenance arm was found to be comparable with regard to outcomes, and favorable in terms of the 18-month OS rate. These findings obviously need to be confirmed in a phase III trial, but they are promising when looking at the overall context.

Could you expand on the role of maintenance therapy?

Are there any studies ongoing with immunotherapy worth mentioning?

What are the biggest challenges remaining in metastatic disease?

Of course, there are going to be multiple trials looking at new drugs with chemotherapy backbones. We have learned that in order to really [attack] pancreatic cancer, we need agents that will engage the tumor for longer periods of time. Immunotherapy has also emerged. This is something we didn't think was possible in metastatic pancreatic cancer. Now, there's hope; we just need to find the right combination. We would love to dismantle the idea that pancreatic cancer is a so-called “cold” tumor.It wasn't something we ever thought would work in pancreatic cancer because we were always just worried about improving outcomes. To be honest, the differences have been quite modest so far at around 2 to 4 months. Patients weren't even living long enough to consider maintenance therapy. Now, we've reached a point with active agents, such as FOLFIRINOX, in fit patients. This question is coming up because we're utilizing dose intensification, and neuropathy is starting to become an issue. We certainly have a lot of work that needs to be done.There are multiple combinations out there. I spoke about the “Grand Slam” regimen, which combines gemcitabine, cisplatin, nab-paclitaxel, (Abraxane), nivolumab (Opdivo), and vitamin D. It was a small sample size, but it had interesting data. We also have a study with chemokine receptors, which are essentially proteins that regulate traffic between the immune system and tumor cells. There are studies looking at combining this in the first-line setting.Logistically, the biggest challenge is getting patients enrolled on clinical trials. The importance of this cannot be overemphasized. We can't change the landscape and define a new standard if only a small percentage of patients are enrolling. We obviously can't make it mandatory, but something needs to be done to bring this to light. Whether it's liquid-based biopsies, tumor testing, or germline testing, there are so many ways we can get the right patients enrolled. We could get more gain.

Dahan L, Phelip J, Malicot K, et al. FOLFIRINOX until progression, FOLFIRINOX with maintenance treatment, or sequential treatment with gemcitabine and FOLFIRI.3 for first-line treatment of metastatic pancreatic cancer: a randomized phase II trial (PRODIGE 35-PANOPTIMOX). J Clin Oncol. 2018;36(15 suppl; abstr 4000). doi: 10.1200/JCO.2018.36.15_suppl.4000.