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In February, the US Food and Drug Administration (FDA) approved irinotecan liposome (Onivyde) as part of a new regimen for first-line metastatic pancreatic adenocarcinoma called NALIRIFOX.
The main difference between NALIRIFOX and a standard go-to regimen for the indication, modified FOLFIRINOX, is that liposomal irinotecan — irinotecan encased in a lipid nanoparticle — is used instead of free irinotecan.
Trial data suggested a better overall response rate, a slight progression-free survival advantage, and potentially fewer adverse events with the liposomal formulation.
The substitution, however, raises the cost of treatment substantially. According to one estimate, a single cycle of FOLFIRINOX costs about $500 at a body surface area of 2 m2, while the equivalent single cycle of NALIRIFOX costs $7800 — over 15-fold more expensive.
While some oncologists have called the NALIRIFOX regimen a potential new standard first-line treatment for metastatic pancreatic adenocarcinoma, others have expressed serious doubts about whether the potential benefits are worth the extra cost.
“I can’t really see a single scenario where I would recommend NALIRIFOX over FOLFIRINOX” Ignacio Garrido-Laguna, MD, PhD, a gastrointestinal oncologist and pancreatic cancer researcher at the University of Utah, Salt Lake City, told this news organization. “Most of us in the academic setting have the same take on this.”
No Head-to-Head Comparison
Instead, the 770-patient NAPOLI 3 trial compared NALIRIFOX — which also includes oxaliplatin, fluorouracil, and leucovorin — with a two-drug regimen, nab-paclitaxel and gemcitabine. In the trial, overall survival and other outcomes were moderately better with NALIRIFOX.
Oncologists have said that the true value of the trial is that it conclusively demonstrates that a four-drug regimen is superior to a two-drug regimen for patients who can tolerate the more intensive therapy.
Eileen M. O’Reilly, MD, the senior investigator on NAPOLI 3, made this point when she presented the phase 3 results at the 2023 ASCO annual meeting.
The trial “answers the question of four drugs versus two” for first-line metastatic pancreatic cancer but “does not address the question of NALIRIFOX versus FOLFIRINOX,” said Dr. O’Reilly, a pancreatic and hepatobiliary oncologist and researcher at Memorial Sloan Kettering Cancer Center in New York City.
Comparing them directly in the study “probably wouldn’t have been in the interest of the sponsor,” said Dr. O’Reilly.
With no head-to-head comparison, oncologists have been comparing NAPOLI 3 results with those from PRODIGE 4, the 2011 trial that won FOLFIRINOX its place as a first-line regimen.
When comparing the trials, median overall survival was exactly the same for the two regimens — 11.1 months. FOLFIRINOX was associated with a slightly higher 1-year survival rate — 48.4% with FOLFIRINOX vs 45.6% with NALIRIFOX.
However, Dr. O’Reilly and her colleagues also highlighted comparisons between the two trials that favored NAPOLI 3.
NAPOLI 3 had no age limit, while PRODIGE subjects were no older than 75 years. Median progression-free survival was 1 month longer among patients receiving NALIRIFOX — 7.4 months vs 6.4 months in PRODIGE — and overall response rates were higher as well — 41.8% in NAPOLI 3 vs 31.6%. Patients receiving NALIRIFOX also had lower rates of grade 3/4 neutropenia (23.8% vs 45.7%, respectively) and peripheral sensory neuropathy (3.5% vs 9.0%, respectively).
The authors explained that the lower rate of neuropathy could be because NALIRIFOX uses a lower dose of oxaliplatin (FOLFIRINOX), at 60 mg/m2 instead of 85 mg/m2.
Is It Worth It?
During a presentation of the phase 3 findings last year, study author Zev A. Wainberg, MD, of the University of California, Los Angeles, said the NALIRIFOX regimen can be considered the new reference regimen for first-line treatment of metastatic pancreatic adenocarcinoma.
The study discussant, Laura Goff, MD, MSCI, of Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, agreed that the results support the NALIRIFOX regimen as “the new standard for fit patients.”
However, other oncologists remain skeptical about the benefits of the new regimen over FOLFIRINOX for patients with metastatic pancreatic adenocarcinoma.
In a recent editorial, Dr. Garrido-Laguna and University of Utah gastrointestinal oncologist Christopher Nevala-Plagemann, MD, compared the evidence for both regimens.
The experts pointed out that overall response rates were assessed by investigators in NAPOLI 3 and not by an independent review committee, as in PRODIGE 4, and might have been overestimated.
Although the lack of an age limit was touted as a benefit of NAPOLI 3, Dr. Garrido-Laguna and Dr. Nevala-Plagemann doubt whether enough patients over 75 years old participated to draw any meaningful conclusions about using NALIRIFOX in older, frailer patients. If anything, patients in PRODIGE 4 might have been less fit because, among other things, the trial allowed patients with serum albumins < 3 g/dL.
On the adverse event front, the authors highlighted the higher incidences of grade 3 or worse diarrhea with NALIRIFOX (20% vs 12.7%) and questioned if there truly is less neutropenia with NALIRIFOX because high-risk patients in NAPOLI 3 were treated with granulocyte colony-stimulating factor to prevent it. The pair also questioned whether the differences in neuropathy rates between the two trials were big enough to be clinically meaningful.
Insights from a recent meta-analysis may further clarify some of the lingering questions about the efficacy of NALIRIFOX vs FOLFIRINOX.
In the analysis, the team found no meaningful difference in overall and progression-free survival between the two regimens. Differences in rates of peripheral neuropathy and diarrhea were not statistically significant, but NALIRIFOX did carry a statistically significant advantage in lower rates of febrile neutropenia, thrombocytopenia, and vomiting.
The team concluded that “NALIRIFOX and FOLFIRINOX may provide equal efficacy as first-line treatment of metastatic pancreatic cancer, but with different toxicity profiles,” and called for careful patient selection when choosing between the two regimens as well as consideration of financial toxicity.
Dr. Garrido-Laguna had a different take. With the current data, NALIRIFOX does not seem to “add anything substantially different to what we already” have with FOLFIRINOX, he told this news organization. Given that, “we can’t really justify NALIRIFOX over FOLFIRINOX without more of a head-to-head comparison.”
The higher cost of NALIRIFOX, in particular, remains a major drawback.
“We think it would be an economic disservice to our healthcare systems if we used NALIRIFOX instead of FOLFIRINOX for these patients on the basis of [NAPOLI 3] data,” Bishal Gyawali, MD, PhD, and Christopher Booth, MD, gastrointestinal oncologists at Queen’s University in Kingston, Ontario, Canada, said in a recent essay.
Dr. Garrido-Laguna and Dr. Nevala-Plagemann reiterated this concern.
Overall, “NALIRIFOX does not seem to raise the bar but rather exposes patients and healthcare systems to financial toxicities,” Dr. Garrido-Laguna and Dr. Nevala-Plagemann wrote in their review.
NAPOLI 3 was funded by Ipsen and PRODIGE 4 was funded by the government of France. No funding source was reported for the meta-analysis. NAPOLI 3 investigators included Ipsen employees. Dr. O’Reilly disclosed grants or contracts from Ipsen and many other companies. Dr. Garrido-Laguna reported institutional research funding from Bristol Myers Squibb, Novartis, Pfizer, and other companies, but not Ipsen. Dr. Nevala-Plagemann is an advisor for Seagen and reported institutional research funding from Theriva. Dr. Gyawali is a consultant for Vivio Health; Dr. Booth had no disclosures. Two meta-analysis authors reported grants or personal fees from Ipsen as well as ties to other companies.
A version of this article appeared on Medscape.com.
In February, the US Food and Drug Administration (FDA) approved irinotecan liposome (Onivyde) as part of a new regimen for first-line metastatic pancreatic adenocarcinoma called NALIRIFOX.
The main difference between NALIRIFOX and a standard go-to regimen for the indication, modified FOLFIRINOX, is that liposomal irinotecan — irinotecan encased in a lipid nanoparticle — is used instead of free irinotecan.
Trial data suggested a better overall response rate, a slight progression-free survival advantage, and potentially fewer adverse events with the liposomal formulation.
The substitution, however, raises the cost of treatment substantially. According to one estimate, a single cycle of FOLFIRINOX costs about $500 at a body surface area of 2 m2, while the equivalent single cycle of NALIRIFOX costs $7800 — over 15-fold more expensive.
While some oncologists have called the NALIRIFOX regimen a potential new standard first-line treatment for metastatic pancreatic adenocarcinoma, others have expressed serious doubts about whether the potential benefits are worth the extra cost.
“I can’t really see a single scenario where I would recommend NALIRIFOX over FOLFIRINOX” Ignacio Garrido-Laguna, MD, PhD, a gastrointestinal oncologist and pancreatic cancer researcher at the University of Utah, Salt Lake City, told this news organization. “Most of us in the academic setting have the same take on this.”
No Head-to-Head Comparison
Instead, the 770-patient NAPOLI 3 trial compared NALIRIFOX — which also includes oxaliplatin, fluorouracil, and leucovorin — with a two-drug regimen, nab-paclitaxel and gemcitabine. In the trial, overall survival and other outcomes were moderately better with NALIRIFOX.
Oncologists have said that the true value of the trial is that it conclusively demonstrates that a four-drug regimen is superior to a two-drug regimen for patients who can tolerate the more intensive therapy.
Eileen M. O’Reilly, MD, the senior investigator on NAPOLI 3, made this point when she presented the phase 3 results at the 2023 ASCO annual meeting.
The trial “answers the question of four drugs versus two” for first-line metastatic pancreatic cancer but “does not address the question of NALIRIFOX versus FOLFIRINOX,” said Dr. O’Reilly, a pancreatic and hepatobiliary oncologist and researcher at Memorial Sloan Kettering Cancer Center in New York City.
Comparing them directly in the study “probably wouldn’t have been in the interest of the sponsor,” said Dr. O’Reilly.
With no head-to-head comparison, oncologists have been comparing NAPOLI 3 results with those from PRODIGE 4, the 2011 trial that won FOLFIRINOX its place as a first-line regimen.
When comparing the trials, median overall survival was exactly the same for the two regimens — 11.1 months. FOLFIRINOX was associated with a slightly higher 1-year survival rate — 48.4% with FOLFIRINOX vs 45.6% with NALIRIFOX.
However, Dr. O’Reilly and her colleagues also highlighted comparisons between the two trials that favored NAPOLI 3.
NAPOLI 3 had no age limit, while PRODIGE subjects were no older than 75 years. Median progression-free survival was 1 month longer among patients receiving NALIRIFOX — 7.4 months vs 6.4 months in PRODIGE — and overall response rates were higher as well — 41.8% in NAPOLI 3 vs 31.6%. Patients receiving NALIRIFOX also had lower rates of grade 3/4 neutropenia (23.8% vs 45.7%, respectively) and peripheral sensory neuropathy (3.5% vs 9.0%, respectively).
The authors explained that the lower rate of neuropathy could be because NALIRIFOX uses a lower dose of oxaliplatin (FOLFIRINOX), at 60 mg/m2 instead of 85 mg/m2.
Is It Worth It?
During a presentation of the phase 3 findings last year, study author Zev A. Wainberg, MD, of the University of California, Los Angeles, said the NALIRIFOX regimen can be considered the new reference regimen for first-line treatment of metastatic pancreatic adenocarcinoma.
The study discussant, Laura Goff, MD, MSCI, of Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, agreed that the results support the NALIRIFOX regimen as “the new standard for fit patients.”
However, other oncologists remain skeptical about the benefits of the new regimen over FOLFIRINOX for patients with metastatic pancreatic adenocarcinoma.
In a recent editorial, Dr. Garrido-Laguna and University of Utah gastrointestinal oncologist Christopher Nevala-Plagemann, MD, compared the evidence for both regimens.
The experts pointed out that overall response rates were assessed by investigators in NAPOLI 3 and not by an independent review committee, as in PRODIGE 4, and might have been overestimated.
Although the lack of an age limit was touted as a benefit of NAPOLI 3, Dr. Garrido-Laguna and Dr. Nevala-Plagemann doubt whether enough patients over 75 years old participated to draw any meaningful conclusions about using NALIRIFOX in older, frailer patients. If anything, patients in PRODIGE 4 might have been less fit because, among other things, the trial allowed patients with serum albumins < 3 g/dL.
On the adverse event front, the authors highlighted the higher incidences of grade 3 or worse diarrhea with NALIRIFOX (20% vs 12.7%) and questioned if there truly is less neutropenia with NALIRIFOX because high-risk patients in NAPOLI 3 were treated with granulocyte colony-stimulating factor to prevent it. The pair also questioned whether the differences in neuropathy rates between the two trials were big enough to be clinically meaningful.
Insights from a recent meta-analysis may further clarify some of the lingering questions about the efficacy of NALIRIFOX vs FOLFIRINOX.
In the analysis, the team found no meaningful difference in overall and progression-free survival between the two regimens. Differences in rates of peripheral neuropathy and diarrhea were not statistically significant, but NALIRIFOX did carry a statistically significant advantage in lower rates of febrile neutropenia, thrombocytopenia, and vomiting.
The team concluded that “NALIRIFOX and FOLFIRINOX may provide equal efficacy as first-line treatment of metastatic pancreatic cancer, but with different toxicity profiles,” and called for careful patient selection when choosing between the two regimens as well as consideration of financial toxicity.
Dr. Garrido-Laguna had a different take. With the current data, NALIRIFOX does not seem to “add anything substantially different to what we already” have with FOLFIRINOX, he told this news organization. Given that, “we can’t really justify NALIRIFOX over FOLFIRINOX without more of a head-to-head comparison.”
The higher cost of NALIRIFOX, in particular, remains a major drawback.
“We think it would be an economic disservice to our healthcare systems if we used NALIRIFOX instead of FOLFIRINOX for these patients on the basis of [NAPOLI 3] data,” Bishal Gyawali, MD, PhD, and Christopher Booth, MD, gastrointestinal oncologists at Queen’s University in Kingston, Ontario, Canada, said in a recent essay.
Dr. Garrido-Laguna and Dr. Nevala-Plagemann reiterated this concern.
Overall, “NALIRIFOX does not seem to raise the bar but rather exposes patients and healthcare systems to financial toxicities,” Dr. Garrido-Laguna and Dr. Nevala-Plagemann wrote in their review.
NAPOLI 3 was funded by Ipsen and PRODIGE 4 was funded by the government of France. No funding source was reported for the meta-analysis. NAPOLI 3 investigators included Ipsen employees. Dr. O’Reilly disclosed grants or contracts from Ipsen and many other companies. Dr. Garrido-Laguna reported institutional research funding from Bristol Myers Squibb, Novartis, Pfizer, and other companies, but not Ipsen. Dr. Nevala-Plagemann is an advisor for Seagen and reported institutional research funding from Theriva. Dr. Gyawali is a consultant for Vivio Health; Dr. Booth had no disclosures. Two meta-analysis authors reported grants or personal fees from Ipsen as well as ties to other companies.
A version of this article appeared on Medscape.com.
In February, the US Food and Drug Administration (FDA) approved irinotecan liposome (Onivyde) as part of a new regimen for first-line metastatic pancreatic adenocarcinoma called NALIRIFOX.
The main difference between NALIRIFOX and a standard go-to regimen for the indication, modified FOLFIRINOX, is that liposomal irinotecan — irinotecan encased in a lipid nanoparticle — is used instead of free irinotecan.
Trial data suggested a better overall response rate, a slight progression-free survival advantage, and potentially fewer adverse events with the liposomal formulation.
The substitution, however, raises the cost of treatment substantially. According to one estimate, a single cycle of FOLFIRINOX costs about $500 at a body surface area of 2 m2, while the equivalent single cycle of NALIRIFOX costs $7800 — over 15-fold more expensive.
While some oncologists have called the NALIRIFOX regimen a potential new standard first-line treatment for metastatic pancreatic adenocarcinoma, others have expressed serious doubts about whether the potential benefits are worth the extra cost.
“I can’t really see a single scenario where I would recommend NALIRIFOX over FOLFIRINOX” Ignacio Garrido-Laguna, MD, PhD, a gastrointestinal oncologist and pancreatic cancer researcher at the University of Utah, Salt Lake City, told this news organization. “Most of us in the academic setting have the same take on this.”
No Head-to-Head Comparison
Instead, the 770-patient NAPOLI 3 trial compared NALIRIFOX — which also includes oxaliplatin, fluorouracil, and leucovorin — with a two-drug regimen, nab-paclitaxel and gemcitabine. In the trial, overall survival and other outcomes were moderately better with NALIRIFOX.
Oncologists have said that the true value of the trial is that it conclusively demonstrates that a four-drug regimen is superior to a two-drug regimen for patients who can tolerate the more intensive therapy.
Eileen M. O’Reilly, MD, the senior investigator on NAPOLI 3, made this point when she presented the phase 3 results at the 2023 ASCO annual meeting.
The trial “answers the question of four drugs versus two” for first-line metastatic pancreatic cancer but “does not address the question of NALIRIFOX versus FOLFIRINOX,” said Dr. O’Reilly, a pancreatic and hepatobiliary oncologist and researcher at Memorial Sloan Kettering Cancer Center in New York City.
Comparing them directly in the study “probably wouldn’t have been in the interest of the sponsor,” said Dr. O’Reilly.
With no head-to-head comparison, oncologists have been comparing NAPOLI 3 results with those from PRODIGE 4, the 2011 trial that won FOLFIRINOX its place as a first-line regimen.
When comparing the trials, median overall survival was exactly the same for the two regimens — 11.1 months. FOLFIRINOX was associated with a slightly higher 1-year survival rate — 48.4% with FOLFIRINOX vs 45.6% with NALIRIFOX.
However, Dr. O’Reilly and her colleagues also highlighted comparisons between the two trials that favored NAPOLI 3.
NAPOLI 3 had no age limit, while PRODIGE subjects were no older than 75 years. Median progression-free survival was 1 month longer among patients receiving NALIRIFOX — 7.4 months vs 6.4 months in PRODIGE — and overall response rates were higher as well — 41.8% in NAPOLI 3 vs 31.6%. Patients receiving NALIRIFOX also had lower rates of grade 3/4 neutropenia (23.8% vs 45.7%, respectively) and peripheral sensory neuropathy (3.5% vs 9.0%, respectively).
The authors explained that the lower rate of neuropathy could be because NALIRIFOX uses a lower dose of oxaliplatin (FOLFIRINOX), at 60 mg/m2 instead of 85 mg/m2.
Is It Worth It?
During a presentation of the phase 3 findings last year, study author Zev A. Wainberg, MD, of the University of California, Los Angeles, said the NALIRIFOX regimen can be considered the new reference regimen for first-line treatment of metastatic pancreatic adenocarcinoma.
The study discussant, Laura Goff, MD, MSCI, of Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, agreed that the results support the NALIRIFOX regimen as “the new standard for fit patients.”
However, other oncologists remain skeptical about the benefits of the new regimen over FOLFIRINOX for patients with metastatic pancreatic adenocarcinoma.
In a recent editorial, Dr. Garrido-Laguna and University of Utah gastrointestinal oncologist Christopher Nevala-Plagemann, MD, compared the evidence for both regimens.
The experts pointed out that overall response rates were assessed by investigators in NAPOLI 3 and not by an independent review committee, as in PRODIGE 4, and might have been overestimated.
Although the lack of an age limit was touted as a benefit of NAPOLI 3, Dr. Garrido-Laguna and Dr. Nevala-Plagemann doubt whether enough patients over 75 years old participated to draw any meaningful conclusions about using NALIRIFOX in older, frailer patients. If anything, patients in PRODIGE 4 might have been less fit because, among other things, the trial allowed patients with serum albumins < 3 g/dL.
On the adverse event front, the authors highlighted the higher incidences of grade 3 or worse diarrhea with NALIRIFOX (20% vs 12.7%) and questioned if there truly is less neutropenia with NALIRIFOX because high-risk patients in NAPOLI 3 were treated with granulocyte colony-stimulating factor to prevent it. The pair also questioned whether the differences in neuropathy rates between the two trials were big enough to be clinically meaningful.
Insights from a recent meta-analysis may further clarify some of the lingering questions about the efficacy of NALIRIFOX vs FOLFIRINOX.
In the analysis, the team found no meaningful difference in overall and progression-free survival between the two regimens. Differences in rates of peripheral neuropathy and diarrhea were not statistically significant, but NALIRIFOX did carry a statistically significant advantage in lower rates of febrile neutropenia, thrombocytopenia, and vomiting.
The team concluded that “NALIRIFOX and FOLFIRINOX may provide equal efficacy as first-line treatment of metastatic pancreatic cancer, but with different toxicity profiles,” and called for careful patient selection when choosing between the two regimens as well as consideration of financial toxicity.
Dr. Garrido-Laguna had a different take. With the current data, NALIRIFOX does not seem to “add anything substantially different to what we already” have with FOLFIRINOX, he told this news organization. Given that, “we can’t really justify NALIRIFOX over FOLFIRINOX without more of a head-to-head comparison.”
The higher cost of NALIRIFOX, in particular, remains a major drawback.
“We think it would be an economic disservice to our healthcare systems if we used NALIRIFOX instead of FOLFIRINOX for these patients on the basis of [NAPOLI 3] data,” Bishal Gyawali, MD, PhD, and Christopher Booth, MD, gastrointestinal oncologists at Queen’s University in Kingston, Ontario, Canada, said in a recent essay.
Dr. Garrido-Laguna and Dr. Nevala-Plagemann reiterated this concern.
Overall, “NALIRIFOX does not seem to raise the bar but rather exposes patients and healthcare systems to financial toxicities,” Dr. Garrido-Laguna and Dr. Nevala-Plagemann wrote in their review.
NAPOLI 3 was funded by Ipsen and PRODIGE 4 was funded by the government of France. No funding source was reported for the meta-analysis. NAPOLI 3 investigators included Ipsen employees. Dr. O’Reilly disclosed grants or contracts from Ipsen and many other companies. Dr. Garrido-Laguna reported institutional research funding from Bristol Myers Squibb, Novartis, Pfizer, and other companies, but not Ipsen. Dr. Nevala-Plagemann is an advisor for Seagen and reported institutional research funding from Theriva. Dr. Gyawali is a consultant for Vivio Health; Dr. Booth had no disclosures. Two meta-analysis authors reported grants or personal fees from Ipsen as well as ties to other companies.
A version of this article appeared on Medscape.com.