A caller four-drug chemotherapy regimen improved endurance outcomes compared with modular therapy successful patients with metastatic metastatic pancreatic ductal adenocarcinoma (mPDAC) successful a planetary signifier 3 proceedings dubbed NAPOLI-3.
Liposomal irinotecan (Onivyde) positive 5-fluorouracil/leucovorin and oxaliplatin (together known arsenic NALIRIFOX) extended some wide and progression-free endurance compared with gemcitabine positive nab-paclitaxel erstwhile utilized arsenic first-line therapy successful treatment-naive patients with mPDAC.
"These results enactment the NALIRIFOX regimen arsenic a caller regimen for the first-line attraction of patients with metastatic PDAC," said pb survey writer Zev A. Wainberg, MD, a prof of medicine astatine University of California, Los Angeles (UCLA) and co-director of the UCLA GI Oncology Program. "This survey indicates that the much assertive chemotherapy attack should beryllium considered for those patients who are capable to tolerate it."
The findings were presented astatine the 2023 ASCO GI Cancers Symposium.
Liposomal irinotecan administered with 5-fluorouracil/leucovorin has been approved successful some the United States and Europe for patients with mPDAC who acquisition illness progression aft attraction with gemcitabine-based therapy. This caller proceedings investigated the attack arsenic a first-line option.
It progressive 770 patients who were randomly assigned to 1 of 2 attraction arms: NALIRIFOX (liposomal irinotecan 50 mg/m2, 5-fluorouracil 2400 mg/m2, leucovorin 400 mg/m2, and oxaliplatin 60 mg/m2; days 1 and 15 of 28-day cycle) oregon gemcitabine 1000 mg/m2 positive nab-paclitaxel 125 mg/m2 (days 1, 8, and 15 of 28-day cycle).
Most patients successful some survey arms were antheral (53.3% and 59.4% for liposomal irinotecan/NALIRIFOX recipient vs the power group, respectively), had astatine slightest 3 metastatic sites (38.9% and 36.4%), had liver metastases (80.2% and 80.4%), and had their main tumor located extracurricular the caput of the pancreas (61.6% and 59.7%).
Most patients (65% successful some arms) were treated extracurricular of North America and East Asia.
"This is genuinely a planetary study, enrolling successful implicit 20 countries, with a premix of some world and assemblage centers," said Wainberg.
At a median follow-up of 16.1 months, 544 events had occurred.
"The survey met its superior endpoint of wide endurance by improving the median from 9.2 months with gemcitabine positive nab-paclitaxel to 11.1 months with NALIFIROX-treated group," said Wainberg. "The hazard ratio was 0.84, with a P worth of .04."
Significant betterment was besides observed successful progression-free survival: 7.4 months for NALIFIROX vs 5.6 months for gemcitabine positive nab-paclitaxel (hazard ratio, 0.69; P < .0001).
The wide effect complaint for liposomal irinotecan/NALIRIFOX vs nab-paclitaxel/gemcitabine was 41.8% vs 36.2%, and the implicit effect complaint was 0.3% successful some arms.
Wainberg noted that astir fractional of the patients successful some groups underwent consequent anticancer therapy (50.5% vs 54.4%); this included systemic treatments, surgery, and radiation therapy.
Grade 3/4 treatment-emergent adverse events reported successful ≥ 10% of patients successful some groups included diarrhea (20.3% vs 4.5%), nausea (11.9% vs 2.6%), hypokalemia (15.1% vs 4.0%), anemia (10.5% vs 17.4%), and neutropenia (14.1% vs 24.5%).
"When 1 looks astatine the nuances successful the patients and the toxicity profiles, we tin spot these 2 regimens person precise antithetic toxicity profiles," Wainberg said. "There was besides little peripheral neuropathy seen successful the NALIRIFOX limb comparative to the nab-paclitaxel/gemcitabine arm."
The differences successful the toxicity profiles were related to the mechanisms of action, Wainberg explained. "No caller information concerns with the NALIRIFOX regimen were identified."
New Reference Regimen
Wainberg concluded that the NALIRIFOX regimen tin beryllium considered the caller notation regimen for first-line attraction of metastatic pancreatic adenocarcinoma. "Hopefully it's thing we tin physique disconnected of successful the future."
Discussant for this paper, Laura Goff, MD, MSCI, an subordinate prof of medicine and the enforcement aesculapian manager for the Cancer Patient Care Center astatine Vanderbilt Ingram Cancer Center, Nashville, Tennessee, agreed.
For "fit patients, these results enactment the NALIRIFOX regimen arsenic the caller notation regimen for first-line attraction of metastatic pancreatic adenocarcinoma," she said.
"It is the caller modular for acceptable patients," she added.
She besides agreed with the authors' decision that NALIRIFOX demonstrated clinically meaningful and statistically important improvements successful wide and progression-free endurance compared with nab-paclitaxel/gemcitabine.
"The information illustration of NALIRFOX was manageable and accordant with the attraction components," she said. "Both regimens had precocious toxicity rates, but their toxicity profiles were different."
Goff pointed retired that precocious rates of toxicity were seen successful some arms, "despite the estimation that gemcitabine/nab-paclitaxel is simply a importantly easier regimen to tolerate. I would reason that these information bash not needfully enactment that."
The survey was funded by Ipsen. Wainberg reported relationships with Amgen, Arcus Bioscience, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, Daiichi Sankyo/Astra Zeneca, Ipsen, Lilly, Merck, Novartis, Pfizer, Plexxikon, PureTech, QED Therapeutics, Seattle Genetics. Goff reported relationships with Agios, ASLAN Pharmaceuticals, AstraZeneca, Basilea, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Exelixis, Genentech, Merck, and QED Therapeutics. Most of the different authors connected the survey had disclosures.
Presented January 20 astatine the 2023 ASCO GI Cancers Symposium. Abstract LBA661
Roxanne Nelson is simply a registered caregiver and an award-winning aesculapian writer who has written for galore large quality outlets and is simply a regular contributor to Medscape.
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