Nick Mulcahy

March 30, 2017

ORLANDO — Pancreatic cancer is projected to become the most common cause of cancer death in the United States in the coming decades as lung cancer deaths continue to drop, said Margaret Tempero, MD, a medical oncologist from the University of California San Francisco.

Citing statistics from the American Cancer Society, Dr Tempero also observed that in 2016, there were more deaths from pancreatic cancer than breast cancer.

Speaking here at the annual meeting of the National Comprehensive Cancer Network (NCCN) 22nd Annual Conference, she recited more sobering statistics about this highly lethal cancer: Eighty percent of patients are diagnosed with advanced unresectable disease, and, of the minority who can be resected, 80% will relapse after adjuvant drug therapy.

"This is a very tough disease!" she exclaimed.

One of the efforts to improve outcomes in the treatment of pancreatic cancer is the relatively "new trend" of using neoadjuvant therapy in patients who have resectable disease, she said at the NCCN meeting.

Dr Tempero told Medscape Medical News that the traditional approach of waiting to administer chemotherapy until after surgery may allow the disease to advance metastatically.

"If you go straight into surgery, it takes time for you to recover. And if you are already harboring micrometastases, then all those cells are going nuts while you are waiting and recovering from surgery," she said.

Preoperative chemotherapy provides "earlier control of the disease" and may give the patient an "added edge" in terms of survival, she continued.

Alok Khorana, MD, a medical oncologist and pancreatic cancer expert at the Taussig Cancer Institute of the Cleveland Clinic in Ohio, agreed with Dr Tempero's assessment of the neoadjuvant trend.

"The use of preoperative treatment is increasing now that we have more effective regimens, such as FOLFIRINOX or gemcitabine/nab-paclitaxel, with decent response rates," he said. FOLFIRINOX consists of fluorouracil, irinotecan, and oxaliplatin.

These regimens have been shown to improve outcomes in metastatic disease in randomized clinical trials, he added. Using these combinations in the neoadjuvant setting has not yet been established in trials but is a logical next step, he suggested.

Which approach is best? "There is no current standard," said Dr Khorana, who was asked for comment. The full list of options includes gemcitabine/nab-paclitaxel (Abraxane, Celgene), FOLFIRINOX or chemoradiation with capecitabine (Xeloda, Genentech), and radiation therapy.

Both he and Dr Tempero agreed that the surgery-first approach in pancreatic cancer does not jibe with what is now understood about the disease — that it appears to spread early on and becomes a systemic (and not a strictly local) treatment issue. And both said a high percentage of patients with resectable disease who undergo "curative" surgery will die of the cancer.

In a 2014 essay, Dr Khorana and colleagues articulated the situation this way: "Analogous to breast cancer, we propose that the Halstedian approach of treating pancreatic cancer as a local, surgical problem should be replaced by Fisher's alternative hypothesis of cancer as a systemic disease."

In her NCCN presentation, Dr Tempero reviewed three clinical trials underway or in the pipeline that are looking at neoadjuvant chemotherapy.

The trials include the in-progress Southwest Oncology Group's S1505, which is comparing combination chemotherapy (FOLFIRINOX) with gemcitabine plus nab-paclitaxel before surgery in patients with resectable disease.

Neoadjuvant chemotherapy is also being used clinically in the United States in “borderline resectable” disease in the hope of downstaging the tumor and increasing the chance that the tumor be fully removed, said Dr Tempero. One of the two new clinical trials in the pipeline will look at this group of patients and neoadjuvant chemotherapy and chemoradiation.

Dr Tempero said that it remains to be seen whether patients with pancreatic cancer will benefit from neoadjuvant treatments — but both breast cancer and colorectal cancer provide examples of malignancies where outcomes have improved with the approach.

In the meantime, currently, patients with resectable disease who are treated with the traditional approach of adjuvant chemotherapy will wait about 8 weeks on average before starting the systemic therapy after surgery, she said.

Dr Tempero reports research funding from Celgene, which markets nab-paclitaxel, and financial ties to other pharmaceutical companies. Dr Khorana reports serving as a consultant or in an advisory role for Eli Lilly and has received research funding from Eli Lilly, ImClone Systems, Gilead Sciences, Merck, and Berg.

National Comprehensive Cancer Network (NCCN) 22nd Annual Conference. Presented March 25, 2017.

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