NALIRIFOX extends OS, PFS for certain patients with pancreatic cancer
CHICAGO — First-line NALIRIFOX significantly extended in OS and PFS vs. gemcitabine and nab-paclitaxel among patients with treatment-naive metastatic pancreatic ductal adenocarcinoma, according to a study presented at ASCO Annual Meeting.
“This study is the first head-to-head comparison of a quadruplet drug combination vs. a doublet combination in untreated metastatic pancreas cancer, as the last positive study in a maintenance setting was a decade ago,” Eileen M. O’Reilly, MD, gastrointestinal oncologist at Memorial Sloan Kettering Cancer Center, told Healio. “This will potentially become a comparator for new studies in development that have the potential to change practice.”
Background and methodology
Researchers conducted the randomized, open-label phase 3 NAPOLI 3 study to investigate the efficacy and safety of 50 mg/m2 liposomal irinotecan, 2,400 mg/m2 5-FU, 400 mg/m2 leucovorin and 60 mg/m2 oxaliplatin (NALIRIFOX) compared with 125 mg/m2 nab-paclitaxel and 1,000 mg/m2 gemcitabine (Gem+NabP) as first-line therapy in patients with treatment-naive metastatic pancreatic ductal adenocarcinoma.
Patients in the investigative group received NALIRIFOX (n = 383) on days 1 and 15 of a 28-day cycle. Patients in the Gem+NabP group (n = 387) received treatment on days 1, 8 and 15 of a 28-day cycle.
OS served as the primary endpoint, with PFS, overall response rate and safety as secondary endpoints.
Median follow-up was 16.1 months.
Results
Researchers reported median OS of 11.1 months in the NALIRIFOX group vs. 9.2 months in the Gem+NabP group (HR = 0.83; 95% CI, 0.7-0.99) and median PFS of 7.4 months vs. 5.6 months (HR = 0.69; 95% CI, 0.58-0.83). The NALIRIFOX group also a longer median duration of response than the Gem+NabP group (7.3 months vs. 5 months).
Grade 3/grade 4 treatment-emergent adverse events that occurred in 10% or more of patients receiving NALIRIFOX vs. Gem+NabP included diarrhea (20.3% vs. 4.5%), nausea (11.9% vs. 2.6%), hypokalemia (15.1% vs. 4%), anemia (10.5% vs. 17.4%) and neutropenia (14.1% vs. 24.5%).
Next steps
Moving forward, an important step will be to get patients familiar with the treatment combination as she hopes it can become a safer option for this patient population, according to O’Reilly.
“Right now, this will be a new quadruplet combination for people to be able to use,” O’Reilly told Healio. “It uses a lower dose of oxaliplatin and I would say is, overall, a somewhat more favorable and tolerable combination. Having it become part of guidelines will be an important step in getting the oncology community more comfortable and familiar with it.”
Perspective
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This is the question we all wanted answered in the field: is the quadruplet regimen in front-line treatment of metastatic or advanced pancreas cancer superior to the doublet of gemcitabine and nab/paclitaxel? We now have level one evidence that the quadruplet is superior.
That being said it doesn’t answer the question of whether NALIRIFOX is superior to what most of us have been using in front-line treatment for those patients who are fit enough with good functional status, which is FOLFIRINOX. So, it’s still unclear whether replacing irinotecan and FOLFIRNOX with nanoliposomal irinotecan is superior. There had been some equipoise regarding what to use in the front line, and I think this takes that away.
The thing we’re going to have to grapple with — and this stems from the fact that there’s no head-to-head comparison of FOLFIRINOX and NALIRIFOX — is the cost. Certainly, this is a lot more expensive in terms of the nanoliposomal irinotecan compared with irinotecan. Without evidence that one is necessarily better than the other, I think it is a challenge.
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O’Reilly E, et al. Abstract 4006. Presented at: ASCO Annual Meeting; June 2-6, 2023: Chicago.