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Interim analysis of a real-world precision medicine platform for molecular profiling of metastatic or advanced
Markus Kieler1, Matthias Unseld1, Daniela Bianconi1
1Department of Medicine I, Division of Oncology, Medical University of Vienna, Wien, Austria.
Background:
High-throughput genomic profiling of tumour specimens facilitates the identification of individual actionable mutations which could be used for individualised targeted therapy. This approach is becoming increasingly more common in the clinic; however, the interpretation of results from molecular profiling tests and efficient guiding of molecular therapies to patients with advanced cancer offer a significant challenge to the oncology community.
Experimental Design:
MONDTI is a precision medicine platform for molecular characterisation of metastatic solid tumours to identify actionable genomic alterations. From 2013 to 2016, comprehensive molecular profiles derived from real-time biopsy specimens and archived tumour tissue samples of 295 patients were performed. Results and treatment suggestions were discussed within multidisciplinary tumour board meetings.
Results:
The mutational profile was obtained from 293 (99%) patients and a complete immunohistochemical (IHC) and cytogenetic profile was obtained in 181 (61%) and 188 (64%) patients. The most frequent cancer types were colorectal cancer (12%), non-Hodgkin's lymphomas (9.8%) and head and neck cancers (7.8%). The most commonly detected mutations were TP53 (39%), KRAS (19%) and PIK3CA (9.5%), whereas ≥1 mutation were identified in 217 (74%) samples. Regarding the results for IHC testing, samples were positive for phospho-mammalian target of rapamycin (phospho-mTOR) (71%), epidermal growth factor receptor (EGFR) (68%), mesenchymal epithelial transition (MET) (56%) and/or platelet-derived growth factor alpha (PDGFRα)-expression (48%). Of the 288 tumour samples with one or more genetic alteration detected, 160 (55.6%) targeted therapy recommendations through 67 multidisciplinary tumour board meetings were made; in 69 (24%) cases, an individual treatment concept was initiated.
Conclusions:
The results reveal that the open concept for all solid tumours characterised for molecular profile and immunotherapy could not only match individualised treatment concepts at a high rate but also underscores the challenges encountered when offering molecularly matched therapies to a patient population with an advanced stage cancer.
Insights
Precision medicine identifies actionable mutations for targeted cancer therapy. While effective, integrating molecular profiling into advanced cancer treatment presents significant challenges for oncologists.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- High-throughput genomic profiling aids in identifying actionable mutations for personalized cancer therapy.
- The clinical application of molecular profiling is increasing, but challenges remain in interpreting results and guiding targeted treatments for advanced cancers.
Purpose of the Study:
- To evaluate the utility of a precision medicine platform (MONDTI) for molecular characterization of metastatic solid tumors.
- To identify actionable genomic alterations and guide individualized targeted therapy.
Main Methods:
- Comprehensive molecular profiling of tumor specimens from 295 patients with metastatic solid tumors (2013-2016).
- Analysis included mutational profiling, immunohistochemistry (IHC), and cytogenetics.
- Results and treatment suggestions were discussed in multidisciplinary tumor board meetings.
Main Results:
- Mutational profiles were obtained for 99% of patients. Common mutations included TP53 (39%), KRAS (19%), and PIK3CA (9.5%).
- IHC revealed frequent positivity for phospho-mTOR (71%), EGFR (68%), MET (56%), and PDGFRα (48%).
- Targeted therapy recommendations were made for 55.6% of samples with detected alterations, leading to individualized treatment concepts in 24% of cases.
Conclusions:
- An open approach to molecular profiling and immunotherapy for solid tumors can facilitate individualized treatment strategies.
- Implementing molecularly matched therapies for patients with advanced cancer remains a complex challenge.
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