Neoadjuvant Chemo Leads to Encouraging Resection Rates in Pancreatic Adenocarcinoma

Davendra Sohal, MD, MPH, associate professor of oncology and urology at Johns Hopkins Medicine

Davendra Sohal, MD, MPH

Aggressively treating pancreatic cancer in the neoadjuvant setting with chemotherapy could improve disease control and increase resection rates, explained Davendra Sohal, MD, MPH, citing results of a recent National Clinical Trials Network phase II trial.

The phase II SWOG S1505 study examined early control of systemic pancreatic disease with neoadjuvant treatment with either modified (mFOLFIRINOX) or gemcitabine/nab-paclitaxel (Abraxane) in patients with resectable pancreatic ductal adenocarcinoma. Of the 147 patients who were initially enrolled, 29% were ineligible due to venous involvement, arterial involvement, and distant disease. Results showed that following neoadjuvant chemotherapy, 77% of patients went to surgery and 73% of them underwent resection.

“This is the first cooperative group study through SWOG in the United States of using chemotherapy upfront for pancreatic cancer,” said Sohal, a medical oncologist at the Cleveland Clinic. “Traditionally, the standard of care for resectable pancreatic cancer is to take [patients] to surgery and then give chemotherapy. In this study, we are testing the novel approach of giving chemotherapy upfront with the hopes that it will control systemic disease more aggressively with better outcomes.”

In an interview with OncLive, Sohal discussed the SWOG S1505 data and other emerging areas of research in pancreatic cancer.

OncLive: Could you provide an overview of the findings of the SWOG S1505 study?

Sohal: Upon central radiology review, which was retrospective based on all of the baseline scans that were uploaded to a central server and reviewed by a blinded radiologist, we found that 29% of patients in the study—approximately 150 patients—had tumors or disease that was more than resectable for protocol criteria.

The findings were related to a number of issues: venous involvement in one-third of cases, more than the allowed arterial involvement in half those cases, and, most surprisingly, suspicion of metastatic disease in almost two-thirds of cases of those were found ineligible. These were indeterminate level lesions—lung lesions or lymph nodes—outside the surgical basin that were never adjudicated as metastatic disease or nonmetastatic disease, but patients were still put on study. That highlights the need for more multidisciplinary care and more objective evaluation of scans before we enroll patients on clinical trials.

What are the next steps following this research?

We have to wait for the final survival results. Two-year overall survival is the primary endpoint of the study. The study finished accrual around April 2018 and, hopefully, by mid-2020, we will get to the primary outcome and see what we find. Hopefully, we will find that patients can derive sustained benefit from the preoperative chemotherapy that they received.

What challenges do we have with this regimen?

It's an aggressive regimen. The good news is that in the adjuvant setting, the clinical trial presented at the 2018 ASCO Annual Meeting showed a very remarkable benefit. Patients had a median survival of almost 4.5 years, which is unheard of. Typically, the median survival for this setting used to be around 2 years. That is a significant improvement. We have, over the last 5 to 8 years, become quite well versed with using this regimen of mFOLFIRINOX.

Is there any rationale for adding FOLFIRNOX to existing regimens?

This is slowly evolving the backbone. Most of the clinical trials, especially in stage IV disease, used to be gemcitabine/nab-paclitaxel based, but with very encouraging data in the adjuvant and metastatic setting, the field is now evolving toward using FOLFIRINOX as a backbone. Studies with agents such as CPI-613 and PEGPH20 are now testing that regimen certainly.

What have been the challenges with trying to explore different regimens?

The number one challenge is acceptability. The field is now evolving toward this. To move a standard of care is quite difficult, especially in a disease such as pancreatic cancer, and to have doctors not take the patient to surgery [upfront] is quite a big ask. However, accrual was very rapid in this national clinical trial on the academic side, as well as community centers, so there is good uptake of the idea.

What other research are you involved in that you're excited about?

We also do clinical trials in metastatic stage IV pancreatic cancer, novel drugs, targeted therapies, immunotherapy combinations, precision oncology, and genomic space research. It is hard to find good targets in pancreatic cancer because it is quite a resistant disease. We are taking baby steps.

Sohal D, McDonough S, Ahmad SA, et al. SWOG S1505: Initial findings on eligibility and neoadjuvant chemotherapy experience with mFOLFIRINOX versus gemcitabine/nab-paclitaxel for resectable pancreatic adenocarcinoma. J Clin Oncol. 2019;37(suppl; abstr 4137). doi: 10.1200/JCO.2019.37.4_suppl.414.