Short-Term S1505 Results Point to Prospective Radiological Review

The standard of care for resectable pancreatic cancer is surgery followed by chemotherapy, but outcomes with this treatment remain suboptimal. Clinical series show 70 to 85 percent of patients die of systemic, as opposed to locoregional, recurrence.

And while new multiagent adjuvant chemotherapy regimens are showing some promise, a significant portion of resectable patients may be too frail to withstand aggressive regimens after surgery.

With this in mind, in 2017, a group of researchers began enrolling patients in S1505, a phase 2 trial run by SWOG through the National Clinical Trials Network of the National Cancer Institute. During the trial, physicians administered multiagent chemotherapy — either mFOLFIRINOX or gemcitabine/nab-paclitaxel — prior to surgery. Both of these regimens are used most often for metastatic (stage 4) pancreatic cancer.

“The idea is to give more aggressive chemotherapy up front, when it’s better tolerated, and then patients who do well on this chemotherapy regimen can go on to surgery, and hopefully that will improve outcomes,” says Davendra P.S. Sohal, MD, MPH, Director of the Clinical Genomics Program at Cleveland Clinic Cancer Center.

Dr. Sohal, who led the national team that was involved in the trial, recently presented the initial results at the Gastrointestinal Cancer Symposium 2019. “We don’t have final outcomes yet; these initial results focused on eligibility and the preoperative chemotherapy experience,” he says.

Radiological review

The researchers enrolled 147 patients from both large academic centers and small community practices, says Dr. Sohal. “They came from real world settings with no cherry-picking from, say, multidisciplinary tertiary care centers.” The median age was 64, 60 were male (59 percent) and 91 (89 percent) were Caucasian.

A radiologist with expertise in abdominal pancreatic imaging blind reviewed scans of each patient’s tumor. This review rendered 29 percent of the patients ineligible because their scans showed that their tumors interfaced with an artery (celiac, common hepatic or superior mesenteric), or because they showed ≥ 180 degree interface between the tumor and a vein wall (portal or superior mesenteric), or because they showed suspicion of metastatic disease.

The fact that 29 percent of the enrolled patients did not, upon further review, meet the study’s protocol illustrated an important point, says Dr. Sohal. “We need to select these patients very carefully. If we want to do these studies, we have to build prospective radiologic review so that there’s a gatekeeper who can say, ‘Okay, this is eligible and this is not.’”

Laying the foundation

Of the remaining patients, 99 started chemotherapy, 86 completed it and 74 underwent surgical resection. The loss of additional patients, Dr. Sohal says, was due to a variety of factors such as chemotherapy toxicity and disease progression. “We do see some drop off and that’s expected,” he says. “These are probably the cases who have bad biology or sicker physiology and so they are not candidates for resection.”

Dr. Sohal says it will be another 18 months or so before his team can assess how many patients met the study’s benchmark of two-year overall survival. So far the initial results are encouraging, he says. “They lay the foundation of this chemotherapy approach so it can be studied more systematically in future prospective trials.”