American Association for Cancer Research Annual Meeting
American Association for Cancer Research Annual Meeting
April 15, 2018
3 min read

Crizotinib induces disease control in ALK-positive inflammatory myofibroblastic tumor

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact

CHICAGO — Crizotinib induced partial or complete tumor shrinkage among half of patients with inoperable, advanced or metastatic ALK-positive inflammatory myofibroblastic tumor, according to results of the phase 2 EORTC 90101 CREATE trial presented at American Association for Cancer Research Annual Meeting.

Investigators reported a 50% objective response rate and a 100% disease control rate among patients with ALK-positive disease. Investigators also observed sporadic activity of crizotinib (Xalkori, Pfizer) in ALK-negative cases.

“In the absence of validated treatment alternatives ... and considering the limitations of nonrandomized drug testing, we propose to redefine crizotinib as the standard of care for patients with locally advanced or metastatic ALK-positive inflammatory myofibroblastic tumor,” Patrick Schöffski, MD, MPH, head of the department of general medical oncology at Leuven Cancer Institute at University Hospitals Leuven in Belgium, said during his presentation.

Inflammatory myofibroblastic tumors — a rare type of soft tissue sarcoma associated with ALK rearrangement or copy number changes — can cause considerable functional disabilities and organ dysfunction. They also can be fatal.

Surgery — including amputations — is standard; however, resection often is not feasible because tumors are close to vital organs. These tumors typically are resistant to radiotherapy and conventional chemotherapy, leaving few options for patients with unresectable or locally recurring disease, according to study background.

“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,” Schöffski said in a press release.

“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,” Schöffski added.

In the EORTC 90101 CREATE trial, Schöffski and colleagues assessed the activity and safety of crizotinib — an inhibitor of ALK, MET and ROS1 — for inflammatory myofibroblastic tumors.

Investigators recruited 35 patients from 13 sites in eight European countries between October 2012 and April 2017. Twenty patients who had centrally confirmed inflammatory myofibroblastic tumors received 250 mg oral crizotinib daily until disease progression.

Twelve eligible patients had ALK-positive disease, defined as at least 15% of tumor cells with rearrangement on fluorescence in situ hybridization or immunohistochemical positivity. Of these, six achieved a confirmed partial response or complete response (overall response rate = 50%; 95% CI, 21.1-78.9). One patient achieved nonconfirmed partial response and five demonstrated stable disease as best response.


One patient with ALK-negative disease was not evaluable due to no measurable disease at baseline.

Among the seven evaluable patients with ALK-negative disease, one (14.3%) achieved partial response, five had stable disease and one had progressive disease.

Researchers reported a higher disease control rate (100% vs. 85.7%) and 1-year PFS rate (73.3% vs. 53.6%) among patients with ALK-positive disease. One-year OS rates were 81.8% (95% CI, 44.7-95.1) in the ALK-positive group and 83.3% (27.3-97.5) in the ALK-negative group.

The ORR and disease control rate results in the ALK-positive group met prespecified criteria for the trial.

Overall, the most common adverse events included nausea (55%), fatigue (45%), blurred vision (45%), vomiting (35%) and diarrhea (35%).

“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 said. “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.” – by Mark Leiser



Schöffski P, et al. Abstract CT045. Presented at: American Association for Cancer Research Annual Meeting; April 14-18, 2018; Chicago.


Disclosures: Pfizer supported the study and provided crizotinib. Schöffski reports an institutional travel grant from Pfizer. Please see the abstract for all other authors’ relevant financial disclosures.