Davendra Sohal, MD, MPH, Discusses Major Takeaways From Key Research in Pancreatic Cancer

Davendra Sohal, MD, MPH

CancerNetwork® spoke with Davendra Sohal, MD, MPH, an associate professor of medicine at the University of Cincinnati, regarding his work presented at the 2021 ASCO Gastrointestinal Cancers Symposium titled “Immunologic predictors of therapeutic response to neoadjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDA) in SWOG S1505."¹

He also detailed recent data published in JAMA Oncology from a first-of-its-kind randomized clinical trial investigating treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) compared with gemcitabine/nab-paclitaxel (Abraxane).²

CancerNetwork®: I was hoping to start with the presentation from the Gastrointestinal Cancers Symposium on immunologic predictors of therapeutic response to neoadjuvant chemotherapy. Could you discuss the differences in tumor cells and immune modulation that were observed between the 2 chemotherapy regimens used in the experimental arm?

Davendra Sohal, MD, MPH: Yes, certainly. This was obviously a translational study of the surgical specimens from SWOG 1505 [NCT02562716]. These patients had received 3 months of chemotherapy, either with the FOLFIRINOX regimen or gemcitabine/nab-paclitaxel, and they then underwent surgery. We took the surgical specimens, [and] the work was performed by Gregory Beatty, [MD, PhD,] at the University of Pennsylvania. He’s a very well-known expert in basic science research in pancreatic cancer. The differences were not very significant between the 2 treatment arms. There was perhaps an increased infiltration of myeloid cells…and a decreased tumor cell population with the FOLFIRINOX arm. It is hard to say what was the cause and what was the effect. Is this just an association or is it really that increased myeloid cells led to decreased tumor cells in the FOLFIRINOX arm compared with gemcitabine/nab-paclitaxel?

CN: Looking at the data, what clinical questions do the findings present? Are there any plans for further investigation of these?

DS: Certainly, the clinical question these findings present is, ‘what is the role of the tumor microenvironment and the tumor immune cell infiltrate in terms of controlling pancreatic cancer?’ We still don’t fully understand it. It does indicate at least from this work that—if you look at all the samples from the SWOG trial compared with historical controls, which were patients who had not received any chemotherapy—with chemotherapy, there were fewer tumor cells within the specimens and there were reduced numbers of immune cells, as well. It is not entirely clear if the reduced number of cells are simply because chemotherapy kills everything, whether tumor cells or immune cells, or that it alters the immune environment within the tumor, which then leads to decreased tumor cells. It at least gives us some clues as to how to design future trials and what to look for.

CN: Shifting gears to the recent data that were published in JAMA Oncology, while the findings didn’t show a direct patient benefit to administering chemotherapy prior to pancreatic surgery, they do suggest it’s possible and safe. What’s the significance of this development? How will it impact treatment of the disease going forward?

DS: Two things. One is that this was the first study to test preoperative chemotherapy in a national clinical trials network in the United States, [and] this was a SWOG trial with 150 patients, approximately. It established safety of this approach, it established feasibility of this approach, it established that neoadjuvant therapy does not lead to harm, and [that] patients can be safely given neoadjuvant therapy and they can undergo surgery. Seventy-three percent of patients had surgery and [went] on to postoperative chemotherapy as well. We established this platform number one. Number two is that [with] the 2 main chemotherapy regimens used in pancreatic cancer, FOLFIRINOX and gemcitabine/nab-paclitaxel, there has never been a head-to-head study. We’ve always debated which one’s better. This study showed that they are essentially equivalent. That answers an important question that, at least in this setting, it doesn’t really matter a whole lot which chemotherapy is given as long as the patient can get it safely. If a patient does not tolerate one, perhaps it is OK to switch to the other one without decreasing the efficacy.

CN: Were there any other findings that were significant in your mind? And how do you anticipate you’ll be able to build upon some of these in future research?

DS: We have established that this can be done, and we have also established that whether we give the chemotherapy pre-surgery or post-surgery, it does not really seem to make a whole lot of difference. We have probably maximized the benefit from chemotherapy. The goal now is to develop some predictors of response…find some predictors where ‘chemo A’ might be better than ‘chemo B’ in a given patient [or define] some early response markers. Maybe [you] give ‘chemo A’ for 2 months and if the response looks good, carry on, otherwise move on to ‘chemo B.’ And then the third component is, as I said, we have maximized the benefit from chemotherapy. The goal now is to try novel therapies and do something more than just these chemotherapy regimens to improve cures.

References:

1. Sohal D, Duong MT, Chang R, et al. Immunologic predictors of therapeutic response to neoadjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDA) in SWOG S1505. Journal of Clinical Oncology. DOI: 10.1200/JCO.2021.39.3_suppl.419

2. Sohal D, Duong MT, Ahmad SA, et al. Efficacy of Perioperative Chemotherapy for Resectable Pancreatic Adenocarcinoma. JAMA Oncology. doi:10.1001/jamaoncol.2020.7328