Desmoid tumors are among "the most confusing of tumors," says an expert in the field.
These rare, locally aggressive tumors arise from fibroblast cells and can occur anywhere in the body — and they have an unpredictable natural history. While they can occasionally become life-threatening when they press down on organs, they can also stop growing or even regress spontaneously, without any intervention.
"There is a 20% known remission rate in patients receiving placebo," commented Laurence H. Baker, DO, from the department of internal medicine, University of Michigan Medical School and the Michigan Medicine Sarcoma Program in Ann Arbor.
"It rarely kills patients, but makes life unpleasant," he told Medscape Medical News.
About one third of patients with desmoid tumors will have progressive or highly symptomatic disease, or both, and will need therapeutic intervention.
However, there is also no consensus on the best treatment plan: it ranges from doing nothing and observing through to surgery, with a range of drug treatments. Historically, patients with desmoid tumors may be treated with tamoxifen (hormonal therapy); anti-inflammatory drugs such as NSAIDs; chemotherapy with a methotrexate–vinblastine regimen; and more recently with tyrosine kinase inhibitors (TKIs) such as imatinib (Gleevec, Novartis) and sorafenib (Nexavar, Bayer).
Pazopanib (Votrient, Novartis) should now be added to the list of treatment options, say researchers reporting what they describe as the first randomized trial of this condition.
The study was published online July 19 in Lancet Oncology.
Not so fast, suggests Baker, who wrote the accompanying editorial. Speaking with Medscape Medical News, he said, "The conclusion that pazopanib could be considered a valid treatment option is premature."
This was an open-label, noncomparative, phase 2 study that randomly assigned 72 patients with progressive desmoid tumors to receive either daily pazopanib 800 mg (n = 48) or standard chemotherapy with methotrexate and vinblastine (n = 24) for 1 year.
After a median follow up of 23.4 months, 46 patients in the pazopanib group and 20 patients in the chemotherapy group were assessable for activity.
More than twice the number of patients receiving pazopanib completed the 1-year treatment schedule (52% vs 23% in the methotrexate–vinblastine group).
The median progression-free survival (PFS) was not reached for either group, but at 6 months, more patients on pazopanib had not progressed. The 6 month PFS was 83.7% for patients on pazopanib vs 45% for patients on methotrexate–vinblastine.
However, Baker noted that the 12-month PFS was similar in the two groups and was higher at 24 months for patients receiving methotrexate–vinblastine (79% vs 67.2% for patients on pazopanib).
"The study investigators fortuitously picked an endpoint that showed benefit for pazopanib," he said, but he also pointed out that this was decided upon before the study was initiated. "However, a more appropriate endpoint would have been to analyze PFS as a continuous variable, which turned out to be quite similar in effect to the survivorship curves" he said.
A partial response (PR) was reported for 37% of patients on pazopanib vs 25% on methotrexate–vinblastine, and stable disease (SD) for 58.7% on pazopanib and 50% on methotrexate–vinblastine.
Dose modifications due to adverse events were reported for 73% of patients on pazopanib and 77% of patients on methotrexate–vinblastine. The investigators noted that the toxicity with pazopanib was manageable and the toxicity profile of the methotrexate–vinblastine used was in line with previous studies.
However, Baker commented: "If three of four patients need dose reductions, how is pazopanib considered tolerable?"
Italiano and colleagues conclude that "pazopanib has clinical activity in patients with progressive desmoid tumors and might be considered a valid treatment option in this rare and disabling disease."
These rare, locally aggressive tumors arise from fibroblast cells and can occur anywhere in the body — and they have an unpredictable natural history. While they can occasionally become life-threatening when they press down on organs, they can also stop growing or even regress spontaneously, without any intervention.
"There is a 20% known remission rate in patients receiving placebo," commented Laurence H. Baker, DO, from the department of internal medicine, University of Michigan Medical School and the Michigan Medicine Sarcoma Program in Ann Arbor.
"It rarely kills patients, but makes life unpleasant," he told Medscape Medical News.
About one third of patients with desmoid tumors will have progressive or highly symptomatic disease, or both, and will need therapeutic intervention.
However, there is also no consensus on the best treatment plan: it ranges from doing nothing and observing through to surgery, with a range of drug treatments. Historically, patients with desmoid tumors may be treated with tamoxifen (hormonal therapy); anti-inflammatory drugs such as NSAIDs; chemotherapy with a methotrexate–vinblastine regimen; and more recently with tyrosine kinase inhibitors (TKIs) such as imatinib (Gleevec, Novartis) and sorafenib (Nexavar, Bayer).
Pazopanib (Votrient, Novartis) should now be added to the list of treatment options, say researchers reporting what they describe as the first randomized trial of this condition.
The study was published online July 19 in Lancet Oncology.
Not so fast, suggests Baker, who wrote the accompanying editorial. Speaking with Medscape Medical News, he said, "The conclusion that pazopanib could be considered a valid treatment option is premature."
DESMOPAZ Trial Results
The new trial, known as DESMOPAZ, was led by Antoine Italiano, MD, PhD, of the Institut Bergonié, Bordeaux, France, on behalf of the French Sarcoma Group.This was an open-label, noncomparative, phase 2 study that randomly assigned 72 patients with progressive desmoid tumors to receive either daily pazopanib 800 mg (n = 48) or standard chemotherapy with methotrexate and vinblastine (n = 24) for 1 year.
After a median follow up of 23.4 months, 46 patients in the pazopanib group and 20 patients in the chemotherapy group were assessable for activity.
More than twice the number of patients receiving pazopanib completed the 1-year treatment schedule (52% vs 23% in the methotrexate–vinblastine group).
The median progression-free survival (PFS) was not reached for either group, but at 6 months, more patients on pazopanib had not progressed. The 6 month PFS was 83.7% for patients on pazopanib vs 45% for patients on methotrexate–vinblastine.
However, Baker noted that the 12-month PFS was similar in the two groups and was higher at 24 months for patients receiving methotrexate–vinblastine (79% vs 67.2% for patients on pazopanib).
"The study investigators fortuitously picked an endpoint that showed benefit for pazopanib," he said, but he also pointed out that this was decided upon before the study was initiated. "However, a more appropriate endpoint would have been to analyze PFS as a continuous variable, which turned out to be quite similar in effect to the survivorship curves" he said.
A partial response (PR) was reported for 37% of patients on pazopanib vs 25% on methotrexate–vinblastine, and stable disease (SD) for 58.7% on pazopanib and 50% on methotrexate–vinblastine.
Dose modifications due to adverse events were reported for 73% of patients on pazopanib and 77% of patients on methotrexate–vinblastine. The investigators noted that the toxicity with pazopanib was manageable and the toxicity profile of the methotrexate–vinblastine used was in line with previous studies.
However, Baker commented: "If three of four patients need dose reductions, how is pazopanib considered tolerable?"
Italiano and colleagues conclude that "pazopanib has clinical activity in patients with progressive desmoid tumors and might be considered a valid treatment option in this rare and disabling disease."
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