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Fred Chen



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    MA23 - Preclinical Models and Genetics of Malignant Pleural Mesothelioma (ID 353)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
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      MA23.01 - Phase II Trial of an Oral FGFR Inhibitor AZD4547 as Second or Third Line Therapy in Malignant Pleural Mesothelioma: Final Results of FRAME Study (Now Available) (ID 2208)

      14:30 - 16:00  |  Author(s): Fred Chen

      • Abstract
      • Presentation
      • Slides

      Background

      Treatment options are limited after first line platinum-based therapy for malignant pleural mesothelioma (MPM). FGFR-9 is a mitogenic ligand that activates the FGF-receptor (FGFR) family and is overexpressed in pleural fluid and tumour samples from mesothelioma patients. In mesothelioma mouse models, FGF-receptor inhibitors reduce tumour burden. Hence, we examined the efficacy of the FGFR tyrosine kinase inhibitor, AZD4547 as second/third line therapy in MPM.

      Method

      From April 2016 to January 2019, we conducted a single-site, single arm, open-label study of AZD4547 in patients with MPM. Eligible patients had histologically or cytologically confirmed mesothelioma, measurable disease and had progressed after first or second line therapy. Patients received oral 80mg twice-daily AZD4547 with protocol dose reductions as required. The primary end point was 6-month progression free survival (PFS6); key secondary endpoints included PFS, response rate, overall survival, and safety and tolerability. Using a Simons' two-stage design, 26 patients would be recruited to the first stage and the study would be declared negative if fewer than 7 (27%) of 26 patients achieved PFS6.

      Result

      24 patients (21 (87%) male), median age 69.5 (range 53-84) were recruited. Histological subtype was epithelioid (83.3%), biphasic (8.3%), sarcomatoid (8.3%). Most patients had one prior regimen (14; 58%). Common toxicities included grade 1 and 2 hyperphosphataemia, nail changes, stomatitis, and ophthalmological changes, consistent with reported toxicities of this drug class. No adverse events required hospitalisation. There were two partial responses (8%); 17 patients (70%) had stable disease (SD) for at least 6 weeks, and 5 patients (21%) had progressive disease as their best response. Three of 24 patients (12%) were progression free at 6 months. Hence, the study fulfilled stopping criteria regardless of further recruitment and was discontinued once the criteria for progressing to stage 2 could not be met. Progression free survival was 3.9 months and overall survival was 9.3 months. One patient remained on study with SD for 16 months, experiencing ongoing grade 2 hyperphosphatemia, alopecia of body and facial hair and grade 2 onycholysis.

      Conclusion

      The FGFR inhibitor AZD4547 was ineffective for patients with MPM who had progressed on first or second line therapy. Continuous grade 2 cutaneous and ocular toxicities were observed with prolonged therapy

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