Expert Point of View: Philip Agop Philip, MD and Alan P. Venook, MD


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Philip Agop Philip, MD, Head of the Multidisciplinary Team for Gastrointestinal and Neuroendocrine Oncology and Neuroendocrine at Karmanos Cancer Institute at Wayne State University, Detroit, was the formal discussant of the paper at the Gastrointestinal Cancers Symposium. He said the positive findings earn nab-paclitaxel/gemcitabine a place in the list of treatment options for metastatic pancreatic cancer, along with gemcitabine with or without erlotinib (Tarceva), and FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) in modified form. “It offers an incremental benefit in this patient population,” he said.

Immediate Question

“The immediate question would be the relative role of nab-paclitaxel/gemcitabine vs FOLFIRINOX in our day-to-day practice, and in our future clinical research activities,” he said, “as well as how to sequence these regimens in a given patient.”

The general consensus among experts at this meeting was that nab-paclitaxel may be better tolerated, and therefore a better fit for elderly or frail patients, but Dr. Philip argued, “This comparison may not be as simple as we would like.” He pointed out that fatigue and diarrhea are more common with FOLFIRINOX, but neuropathy is more common with nab-paclitaxel/gemcitabine.* “The nature of the neuropathy is different, however, especially with regard to its reversibility,” he added.

In terms of efficacy, Dr. Philip judged FOLFIRINOX to be the clear winner, as overall survival in the pivotal French trial was 11.1 months, vs 6.8 months with gemcitabine alone.1 “This begs the question as to whether the study populations may have been dissimilar,” he suggested, noting that MPACT recruited patients “from different corners of the world,” whereas the FOLFIRINOX study was from multiple centers (in one country, France) with expertise in treating this disease.

‘Too Many Variables’

The same question struck Alan P. Venook, MD, the Madden Family Distinguished Professor of Medical Oncology and Translational Research and Chief of Gastrointestinal Oncology at the University of California, San Francisco. In an interview with The ASCO Post, Dr. Venook said the results appear to be “far superior” with FOLFIRINOX but the patients in the FOLFIROINOX study may have been healthier or had less advanced disease.

“But you can’t tell, even by looking at the baseline characteristics. There are too many variables,” he said. Given the worldwide study population, the patients in the MPACT trial may also have received less consistently good care than the FOLFIRINOX study population, who were all treated at Centers of Excellence with expertise in pancreas cancer, such that the benefits of the new regimen would be “diluted,” he said.

“I do think this will be a standard treatment, but wonder if FOLFIRINOX is just more effective than nab-paclitaxel/gemcitabine, and I would like to know if it can match up against FOLFIRINOX,” he concluded, suggesting that a head-to-head comparison could be a worthy research pursuit by the cooperative groups. The analysis of biomarker data in the study will also be important, to see if there is a way to select patients likelier to benefit from the new combination. “The biomarker SPARC has been discussed in this context, and there will be an analysis, but I am disappointed the information presented did not include SPARC.”

While the novel regimen may be more tolerable, he observed, “it was no bargain, either, as 4% of each arm in the study died of complications related to treatment. This also may reflect care received at some of the study sites,” he suggested. He further noted that an alert went out to the investigators early in the trial because of an excess of deaths in the experimental arm. While the study protocol was not amended, a number of recommendations for the management of toxicities were emphasized.

“I do believe this is better tolerated than FOLFIRINOX was in the studies, although we are exploring less intense versions of the regimen [FOLFIRINOX],” he said. “The critical question is, when you see a patient with metastatic pancreatic cancer, how will you treat him now? With nab-paclitaxel/gemcitabine, or with FOLFIRINOX? Until proven otherwise, in the patient with a good performance status, I will still use FOLFIRINOX.” ■

Disclosure: Drs. Philip and Venook reported no potential conflicts of interest.

Reference

1. Conroy T, Desseigne F, Ychou M, et al: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817-1825, 2011.


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