Among patients with inoperable, advanced, or metastatic ALK-positive inflammatory myofibroblastic tumour, 50 percent were confirmed to have partial or complete tumour shrinkage after treatment with the ALK-targeted anticancer therapeutic crizotinib, according to data from the phase IIEORTC 90101 clinical trial, presented at the AACR Annual Meeting 2018, April 14–18.

This study is being simultaneously published in The Lancet Respiratory Medicine.

Inflammatory myofibroblastic tumour is a very rare type of soft tissue sarcoma.

Soft tissue sarcomas themselves account for just 1 percent of all solid tumor diagnoses, and there are no reliable records of the incidence and mortality rates for inflammatory myofibroblastic tumour, 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 tumours 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 tumours to vital organs,” said Schöffski. “Inflammatory myofibroblastic tumours are usually resistant to conventional chemotherapy and radiotherapy, so patients with unresectable or locally recurring disease have few treatment options"

Since many inflammatory myofibroblastic tumours have ALK gene rearrangements, Schöffski set out to assess the efficacy of the ALK inhibitor crizotinib as a potential treatmentfor patients with this disease.

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 percent; two had a confirmed complete response and four had a confirmed partial response.

Among the seven evaluable patients with ALK-negative inflammatory myofibroblastic tumors, it was 14.3 percent.

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 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 percent among the 12 evaluable patients with ALK-positive inflammatory myofibroblastic tumours and 85.7 percent among the seven evaluable patients with ALK-negative disease.

At data cut-off, on November 9, 2017, the median duration of response among the patients with ALK-positive inflammatory myofibroblastic tumours was 9.0 months. Four of these patients are still responding and remain on treatment.

“The NCCN [National Comprehensive Cancer Network] began recommending the off-label use of crizotinib as a treatment for ALK-positive inflammatory myofibroblastic tumours a few years ago, after a single ALK-positive patient was reported to benefit,” said Schöffski. “Our data in predominantly adult patients with inflammatory myofibroblastic tumours, 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 tumour 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,”Schöffski added.“The inclusion in our trial of a group of patients with ALK-negative inflammatory myofibroblastic tumours 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.”

Schöffskia and colleagues at 13 sites in eight 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 78.

Among the patients with ALK-positive tumors, the median age was 35.5 years, the youngest was 21 years old, and the oldest 69.

According to 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, explained Schöffski.

This study was an investigator-initiated study with the European Organisation for Research and Treatmentof Cancer (EORTC) as the legal sponsor.

Pfizer Inc. supported the study and provided crizotinib.

Schöffski received an institutional travel grant from Pfizer Inc.

Source: AACR