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Expert Point of View: Philip A. Philip, MD, PhD, FRCP


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The study’s invited discussant, Philip A. Philip, MD, PhD, FRCP, Professor of Oncology, Pharmacology, and Medicine and the Kathryn Cramer Endowed Chair in Cancer Research at Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, asked whether another triplet regimen was needed for pancreatic cancer. However, he added, “although the efficacy of NALIRIFOX [liposomal irinotecan, leucovorin, fluorouracil, oxaliplatin] appears similar to, or only slightly better than, current standards, its tolerability may be better. Objective responses are within what we expect with combinations, and progression-free and overall survival may be slightly better, but what really attracted my attention is the tolerability profile.”

Philip A. Philip, MD, PhD, FRCP

Philip A. Philip, MD, PhD, FRCP

Dr. Philip illustrated this by showing a comparison of findings with those from the control arms of the RESOLVE study of gemcitabine/nab-paclitaxel1 and the SWOG S1313 trial of modified FOLFIRINOX [leucovorin, fluorouracil, irinotecan, oxaliplatin]2 (Table 1). In particular, fatigue and neuropathy were less common with NALIRIFOX than wither either regimen, and gastrointestinal toxicity was less common than with modified FOLFIRINOX. Neutropenia was still significant, he acknowledged, “but remember, the protocol did not specify the use of growth factors.”

Dr. Philip also noted that the NALIRIFOX population was “on the better side,” with a median age younger than 60, an inclusion of patients with stage III disease (9.4%), and a female predominance over males.

In Comparison With Two Standards

Placing the novel front-line regimen in a pro-and-con context with the two standards, Dr. Philip concluded that its efficacy is “similar to or better than” that of gemcitabine/nab-paclitaxel. In addition, fatigue and neuropathy occur less often with the novel regimen; however, all patients require placement of ports and may need growth factor support.

“Compared with modified FOLFIRINOX,” he added, its efficacy is “probably similar,” but it has the advantage of less gastrointestinal toxicity, less neurotoxicity, and less fatigue. Compared with either of the standard regimens, NALIRIFOX also would be associated with issues of “accessibility and cost,” he noted.

Such concerns aside, Dr. Philip commented: “This preliminary phase I/II study supports a favorable therapeutic index for NALIRIFOX as a front-line treatment of advanced pancreatic cancer…. It may become a future option, but we await the results of the phase III NAPOLI-3 trial, which is randomizing NALIRIFOX vs gemcitabine/nab-paclitaxel.” 

DISCLOSURE: Dr. Philip has received honoraria from Array BioPharma, AstraZeneca, Bayer, Blueprint, Bristol-Myers Squibb, Celgene, Ipsen, Merck, Syncore, and TriSalus; has served as a consultant or advisor to Celgene, Ipsen, Merck, Sobi, and TriSalus; has participated in a speakers bureau for Bayer, Celgene, Advanced Accelarator Applications, Incyte, and Ipsen; has received institutional research funding from Advanced Accelerator Applications, Aslan Pharmaceuticals, Bayer, Beigene, Boston Biomedical, Daiichi Sankyo, Forty Seven, Geistlich, Genentech, Halozyme, Immunomedics, Incyte, Karyopharm Therapeutics, Lilly, Merck, Merus, Natera, Novartis, Novocure, Plexxikon, QED, Rafael, Regeneron, Seattle Genetics, Syncore, Taiho Pharmaceutical, and TYME; has been reimbursed for travel, accommodations, or other expenses by AbbVie, Celgene, Syncore, and Rafael; and has held uncompensated relationships with Caris, Merus, and Rafael.

REFERENCES

1. Tempero M, Oh D, Macarulla T, et al: Ibrutinib in combination with nab-paclitaxel and gemcitabine as first-line treatment for patients with metastatic pancreatic adenocarcinoma: Results from the phase 3 RESOLVE study. ESMO World Congress on Gastrointestinal Cancer 2019. Abstract O-002.

2. Ramanathan RK, McDonough SL, Philip PA, et al: Phase IB/II randomized study of FOLFIRINOX plus pegylated recombinant human hyaluronidase vs FOLFIRINOX alone in patients with metastatic pancreatic adenocarcinoma: SWOG S1313. J Clin Oncol 37:1062-1069, 2019.


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