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SAN DIEGO -- A preoperative combination of chemotherapy and immunotherapy (IO) appeared safe and effective for borderline resectable pancreatic cancer in a small pilot study, a researcher reported here.

In the phase I/II trial, neoadjuvant treatment with modified FOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) plus nivolumab (Opdivo) was associated with favorable rates of R0 resection, along with a median progression-free survival of 21.9 months and median overall survival (OS) of 34.6 months, with longer survival for those who successfully went on to surgery, according to Zev Wainberg, MD, of the University of California Los Angeles School of Medicine.

Prior studies of chemotherapy/IO in the have largely failed, he noted, but the current results support ongoing investigations in less-advanced disease.

"Instead of exclusively studying it in metastatic disease, we need to be studying these drugs earlier on in both borderline and locally advanced disease to understand the impact of these drugs on tumor biology," said Wainberg at the annual meeting of the American Association for Cancer Research (AACR).

The 28 patients in this study received modified FOLFIRINOX plus the PD-1 checkpoint inhibitor nivolumab for 3 to 6 months. If, after 3 months, patients were downstaged to resectable disease, they were eligible for an attempt at R0 resection. If not, they continued treatment for another 3 months.

Of the 28 patients, 22 underwent surgery (79%) -- 21 achieving R0 resections and one achieving an R1. Surgery resulted in two pathologic complete responses, two near complete responses, and 15 partial responses.

Patients with borderline resectable cancer account for about 20% of pancreatic cancer patients. These are patients with tumors that are considered to be resectable -- with or without vascular reconstruction -- but are at high risk for positive margins. Achieving an R0 (negative margin) resection, rather than an R1 resection (where microscopically margins still demonstrate the presence of tumor), is critical as that is associated with longer survival, Wainberg noted.

"The quick time for an R0 resection is very important for this disease because that has been associated with prognosis, but part of the challenge is how to introduce these drugs in the neoadjuvant space, because adjuvant chemo and adjuvant treatment -- generally speaking -- for pancreatic cancer is very difficult," he said. "Trying to move drugs up front is what we are getting at, and in that respect we were very pleased with the progression-free and overall survival outcomes."

AACR session moderator Alice Ho, MD, of Duke University Medical Center in Durham, North Carolina, said the 79% resection rate "sounds pretty stunning."

Wainberg noted that the Alliance A021501 study suggested R0 resection rates of about 70-75% with chemotherapy, but added that what he and his team were trying to accomplish in the current study was to use neoadjuvant therapy to reduce recurrences as well.

Study participants in the phase I/II trial had a median age of 67.5 years, and 57% were male. Baseline ECOG Performance Status score was 0 in 61% of people (indicating full activity) and 1 in the remaining 39% (restricted in physically strenuous activity but otherwise ambulatory). Patients completed a median 5.5 cycles of treatment, and median follow-up for survival outcomes was 25.6 months.

The primary endpoint was safety and secondary endpoints included resection rates and survival endpoints.

Survival was longer for those who had surgery, with Kaplan-Meier estimates of 27.3 months for progression-free survival and 44 months for OS. Overall, the 12- and 18-month OS rates were 82% and 77%, respectively, "higher than historical controls," Wainberg observed.

The Alliance trial, which established preoperative modified FOLFIRINOX (without radiation) as the reference regimen for the current study, had an 18-month OS rate of 66.7% and a median OS of 29.8 months.

Regarding safety, half of the patients in the study had grade ≥3 adverse events, all which were exclusively attributed to chemotherapy. Importantly, he added that there were no grade 2 postoperative fistulas -- a concern after pancreatic cancer resection -- and no postoperative complications.

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