Irinotecan liposome injection regimen ‘a new reference’ for metastatic pancreatic cancer
Irinotecan liposome injection combined with 5-FU/leucovorin and oxaliplatin prolonged OS compared with nab-paclitaxel and gemcitabine as initial treatment for patients with metastatic pancreatic ductal adenocarcinoma, study results showed.
The irinotecan liposome injection regimen, known as NALIRIFOX, also exhibited a manageable safety profile consistent with that of each treatment component, according to the findings, presented at ASCO Gastrointestinal Cancers Symposium.
“These results support the NALIRIFOX regimen as a new reference regimen for the first-line treatment of patients with metastatic pancreatic cancer, and hopefully something we can build off of in the future,” Zev A. Wainberg, MD, co-director of the GI oncology program at University of California, Los Angeles and researcher at UCLA Jonsson Comprehensive Cancer Center, said during a presentation.
Background, methodology
Irinotecan liposome injection (Onivyde, Ipsen) with 5-FU/leucovorin has been FDA approved for adults with metastatic pancreatic cancer who experience progression on gemcitabine-based therapy. The NALIRIFOX regimen, consisting of 50 mg/m2 irinotecan liposome injection, 2,400 mg/m2 5-FU, 400 mg/m2 leucovorin and 60 mg/m2 oxaliplatin, showed antitumor activity as first-line therapy in a previous phase 1/phase 2 study.
In the global, randomized phase 3 NAPOLI 3 trial, Wainberg and colleagues tested the safety and efficacy of NALIRIFOX vs. gemcitabine and nab-paclitaxel (Abraxane, Bristol Myers Squibb) among 770 patients with untreated metastatic pancreatic ductal adenocarcinoma.
The NALIRIFOX group (n = 383) and gemcitabine/nab-paclitaxel group (n = 387) had similar baseline characteristics, including median age (64 years vs. 65 years) and number of metastatic sites (three or greater, 38.9% vs. 36.4%).
OS served as the primary endpoint. Secondary endpoints included PFS and objective response rate per investigator assessment.
Median follow-up was 16.1 months (95% CI, 15.3-16.8). At data cutoff on July 23, 2022, 96.1% of patients on gemcitabine/nab-paclitaxel and 85.1% of patients on NALIRIFOX had discontinued treatment, mostly due to disease progression.
Results
Compared with the gemcitabine/nab-paclitaxel group, the NALIRIFOX group had significantly longer median OS (11.1 months vs. 9.2 months; HR = 0.83; 95% CI, 0.7-0.99), and median PFS (7.4 months vs. 5.6 months; HR = 0.69; 95% CI, 0.58-0.83), with an OS and PFS benefit observed across subgroups. The NALIRIFOX group also had a higher objective response rate (41.8%; 95% CI, 36.8-46.9) than the gemcitabine/nab-paclitaxel group (36.2%; 95% CI, 31.4-41.2), and a lower percentage of patients who received NALIRIFOX went on to receive subsequent anticancer therapy (50.5% vs. 54.4%).
Median duration of treatment was longer with NALIRIFOX (24.2 weeks vs. 17.5 weeks), but researchers observed no significant differences between the groups in all-grade (99.7% vs. 99.2%) or grade 3 or greater (87% vs. 86%) treatment-emergent adverse events.
“There were no significant differences between the arms with respect to serious treatment emergent-adverse events or treatment-adverse events attributed to death caused by any of the components of the regimen,” Wainberg said. “However, when one looks at the nuances in the patients and the toxicity profiles, we can see these two regimens have very different toxicity profiles.”
The most common grade 3/grade 4 treatment-emergent adverse events among patients who received NALIRIFOX vs. gemcitabine/nab-paclitaxel included diarrhea (20.3% vs. 4.5%), hypokalemia (15.1% vs. 4%), neutropenia (14.1% vs. 24.5%), nausea (11.9% vs. 2.6%) and anemia (10.5% vs. 17.4%).
Implications
The results indicate the more aggressive chemotherapy approach should be considered for patients who can tolerate it, Wainberg said in a UCLA Health press release.
“There have been several chemotherapy regimens used to treat newly diagnosed, metastatic pancreas cancer, but there have been few head-to-head comparisons to see which regimen would produce a longer overall survival,” Wainberg said in the release. “These trials help answer critically important treatment questions for all who treat pancreas cancer.”
References:
- A 4-drug chemotherapy regimen improves survival in stage 4 pancreas cancer (press release) Available at: www.uclahealth.org/news/4-drug-chemotherapy-regimen-improves-survival-stage-4. Published Jan. 20, 2023. Accessed Jan. 24, 2023.
- Wainberg ZA, et al. Abstract LBA661. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 19-21, 2023; San Francisco.
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Wainberg ZA, et al. Abstract LBA661. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 19-21, 2023; San Francisco.