Nationwide evaluation of mutation-tailored treatment of gastrointestinal stromal tumors in daily clinical practice

Background Molecular analysis of KIT and PDGFRA is critical for tyrosine kinase inhibitor treatment selection of gastrointestinal stromal tumors (GISTs) and hence recommended by international guidelines. We performed a nationwide study into the application of predictive mutation testing in GIST patients and its impact on targeted treatment decisions in clinical practice. Methods Real-world clinical and pathology information was obtained from GIST patients with initial diagnosis in 2017-2018 through database linkage between the Netherlands Cancer Registry and the nationwide Dutch Pathology Registry. Results Predictive mutation analysis was performed in 89% of the patients with high risk or metastatic disease. Molecular testing rates were higher for patients treated in expertise centers (96%) compared to non-expertise centers (75%, P < 0.01). Imatinib therapy was applied in 81% of the patients with high risk or metastatic disease without patient's refusal or adverse characteristics, e.g., comorbidities or resistance mutations. Mutation analysis that was performed in 97% of these imatinib-treated cases, did not guarantee mutation-tailored treatment: 2% of these patients had the PDGFRA p.D842V resistance mutation and 7% initiated imatinib therapy at the normal instead of high dose despite of having a KIT exon 9 mutation. Conclusion In conclusion, nationwide real-world data show that over 81% of the eligible high risk or metastatic disease patients receive targeted therapy, which was tailored to the mutation status as recommended in guidelines in 88% of cases. Therefore, still 27% of these GIST patients misses out on mutation-tailored treatment. The reasons for suboptimal uptake of testing and treatment require further study

Micro-costing diagnostics in oncology:from single-gene testing to whole- genome sequencing

Purpose: Predictive diagnostics play an increasingly important role in personalized medicine for cancer treatment. Whole-genome sequencing (WGS)-based treatment selection is expected to rapidly increase worldwide. This study aimed to calculate and compare the total cost of currently used diagnostic techniques and of WGS in treatment of non-small cell lung carcinoma (NSCLC), melanoma, colorectal cancer (CRC), and gastrointestinal stromal tumor (GIST) in the Netherlands. Methods: The activity-based costing (ABC) method was conducted to calculate total cost of included diagnostic techniques based on data provided by Dutch pathology laboratories and the Dutch-centralized cancer WGS facility. Costs were allocated to four categories: capital costs, maintenance costs, software costs, and operational costs. Results: The total cost per cancer patient per technique varied from € 58 (Sanger sequencing, three amplicons) to € 2925 (paired tumor-normal WGS). The operational costs accounted for the vast majority (over 90%) of the total per cancer patient technique costs. Conclusion: This study outlined in detail all costing aspects and cost prices of current and new diagnostic modalities used in treatment of NSCLC, melanoma, CRC, and GIST in the Netherlands. Detailed cost differences and value comparisons between these diagnostic techniques enable future economic evaluations to support decision-making

Rationale and Study Design of the IRENE-Trial (NVALT-16):A Phase II Trial to Evaluate Iressa Rechallenge in Advanced NSCLC Patients With an Activating EGFR Mutation Who Responded to an EGFR-TKI Used As First-Line or Previous Treatment

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown improved progression-free survival (PFS) and overall survival (OS) over chemotherapy in a molecularly defined subgroup of advanced non-small-cell lung cancer (NSCLC) patients (ie, patients with an activating mutation in the EGFR gene). Nevertheless, all EGFR-mutated NSCLC patients develop TKI resistance eventually and there is no registered treatment or therapeutic strategy available for these patients. Several retrospective or small cohort studies have described patients who re-responded to EGFR-TKI treatment after a TKI-free interval ('drug holiday'). To date, no large prospective evaluation of the clinical effects of EGFR-TKI rechallenge in EGFR-mutated NSCLC patients has been performed. PATIENTS AND METHODS: The IRENE (Iressa RE-challenge in advanced, EGFR-mutated NSCLC patients who responded to an EGFR-TKI used as first-line or previous treatment) (Dutch association for pulmonologists [NVALT]-16) trial is a multicenter, open-label, single-arm, single-stage, phase II study to evaluate gefitinib rechallenge in EGFR-mutated NSCLC patients who were previously treated with a TKI followed by a subsequent line of treatment (excluding EGFR-TKIs). The primary objective is disease control rate according to Response Evaluation Criteria in Solid Tumors criteria. Secondary objectives are objective response rate, PFS, OS, mutation characterization of sequential biopsies, VeriStrat correlation to PFS and OS, analysis of tumor-derived RNA in blood platelets and analysis of cell-free DNA in blood plasma. RESULTS: The IRENE (NVALT-16) trial will evaluate the safety, efficacy, and feasibility of readministration of gefitinib after an EGFR-TKI-free interval in EGFR-mutated NSCLC patients. CONCLUSION: The study will evaluate gefitinib re-challenge in EGFR-mutated NSCLC patients. The study will also provide more insight into the dynamic development of molecular characteristics of EGFR-mutated NSCLC along the course of the disease

Molecular tumour boards and molecular diagnostics for patients with cancer in the Netherlands: experiences, challenges, and aspirations

Advances in molecular tumour diagnostics and the number of targeted therapies increase rapidly. Molecular tumour boards (MTBs) are designated to interpret these data and provide clinical recommendations. Not all patients with cancer have access to advice of an MTB. We aimed to determine the current status, opportunities, and challenges of the organisation of MTBs in the Netherlands. We interviewed several stakeholders about their experiences with an MTB, using template analysis. Most clinicians and patient representatives underscore the significance of an MTB, because it can stimulate rational treatment options, enrolment in clinical trials, and interdisciplinary knowledge transfer. Health insurance companies and financial managers are concerned about increasing costs. Registries to assess the clinical benefit of MTBs, guidelines on quality control, financial agreements, and logistical resources are lacking. The national organisation of MTBs and a registry of molecular and clinical data are important issues to address