Among patients with inoperable, advanced, or metastatic ALK-positive inflammatory myofibroblastic tumor, 50% were confirmed to have partial or complete tumor shrinkage after treatment with the ALK-targeted anticancer therapeutic agent crizotinib (Xalkori), according to data from the phase II EORTC 90101 clinical trial, presented at the 2018 American Association for Cancer Research (AACR) Annual Meeting, April 14–18 (Abstract CT045). This study was simultaneously published by Schöffski et al in The Lancet Respiratory Medicine.
Inflammatory myofibroblastic tumor is a very rare type of soft-tissue sarcoma. Soft-tissue sarcomas in general account for just 1% of all solid tumor diagnoses, and there are no reliable records of the incidence and mortality rates for inflammatory myofibroblastic tumor, explained Patrick Schöffski, MD, MPH, Head of the Department of General Medical Oncology at the Leuven Cancer Institute, University Hospitals Leuven, Belgium, and principal investigator in the Laboratory of Experimental Oncology at the Catholic University of Leuven (KU Leuven).
“Inflammatory myofibroblastic tumors can cause significant functional disabilities, organ dysfunction, and death. Surgery, including amputations and other debilitating interventions, is the mainstay of treatment, but complete resection is often not possible because of the proximity of the tumors to vital organs,” said Dr. Schöffski. “Inflammatory myofibroblastic tumors are usually resistant to conventional chemotherapy and radiotherapy, so patients with unresectable or locally recurring disease have few treatment options.”
Since many inflammatory myofibroblastic tumors have ALK gene rearrangements, Dr. Schöffski set out to assess the efficacy of the ALK inhibitor crizotinib as a potential treatment for patients with this disease.
Dr. Schöffski and colleagues at 13 sites in 8 European countries recruited 35 patients with a local diagnosis of inflammatory myofibroblastic tumor to the EORTC 90101 trial. Twenty of these patients were confirmed centrally to have the disease and received crizotinib. The median age of the patients was 45.5 years, the youngest was 15 years old, and the oldest was 78. Among patients with ALK-positive tumors, the median age was 35.5 years, the youngest was 21 years old, and the oldest was 69.
Findings of EORTC 90101
In the EORTC 90101 clinical trial, the objective response rate among the 12 evaluable patients with ALK-positive inflammatory myofibroblastic tumors who received crizotinib was 50%; 2 had a confirmed complete response, and 4 had a confirmed partial response. Among the 7 evaluable patients with ALK-negative inflammatory myofibroblastic tumors, the objective response rate was 14.3%. Objective response rate was the primary endpoint for the trial because of a lack of reliable reference data on progression-free survival for patients with this rare cancer at the time the trial was designed, explained Dr. Schöffski.
Disease control rate, defined as the percentage of patients who had a complete response, partial response, or stable disease, was one of the secondary endpoints. The disease control rate was 100% among the 12 evaluable patients with ALK-positive inflammatory myofibroblastic tumors and 85.7% among the 7 evaluable patients with ALK-negative disease.
At data cutoff, on November 9, 2017, the median duration of response among patients with ALK-positive inflammatory myofibroblastic tumors was 9.0 months. Four of these patients are still responding and remain on treatment.
“The [National Comprehensive Cancer Network] began recommending the off-label use of crizotinib as a treatment for ALK-positive inflammatory myofibroblastic tumors a few years ago, after a single ALK-positive patient was reported to benefit,” said Dr. Schöffski. “Our data in predominantly adult patients with inflammatory myofibroblastic tumors, combined with recently published data for children with this disease, support this recommendation and suggest that crizotinib should be considered the standard of care for patients with ALK-positive inflammatory myofibroblastic tumor who cannot be treated with surgery.”
“Our study highlights how identifying the genetic drivers of a rare type of cancer can be used to find a new precision medicine for patients who otherwise have few treatment options,” Dr. Schöffski added. “The inclusion in our trial of a group of patients with ALK-negative inflammatory myofibroblastic tumors provides valuable insight into the selectivity of crizotinib and our understanding of this rare disease, even if we cannot formally compare the outcomes for the ALK-positive and -negative groups.”
According to Dr. Schöffski, limitations of the trial include that it is a noncomparative, single-arm study with a relatively small number of patients. However, given the disease prevalence a more definitive, randomized, comparative trial would not be possible, he explained.
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