Abstract
Advanced therapy-refractory solid tumors bear a dismal prognosis and constitute a major challenge in offering effective treatment strategies. In this real-world retrospective analysis of our precision medicine platform MONDTI, we describe the molecular profile of 554 patients diagnosed with 17 different types of advanced solid tumors after failure of all standard treatment options. In 304 cases (54.9% of all patients), a molecular-driven targeted therapy approach could be recommended, with a recommendation rate above 50% in 12 tumor entities. The three highest rates for therapy recommendation per tumor classification were observed in urologic malignancies (90.0%), mesothelioma (78.6%), and male reproductive cancers (71.4%). Tumor type (p = 0.46), expression of p-mTOR (p = 0.011), expression of EGFR (p = 0.046), and expression of PD-L1 (p = 0.023) had a significant impact on the targeted therapy recommendation rate. Therapy recommendations were significantly more often issued for men (p = 0.015) due to gender-specific differences in the molecular profiles of patients with head and neck cancer and malignant mesothelioma. This analysis demonstrates that precision medicine was feasible and provided the basis for molecular-driven therapy recommendations in patients with advanced therapy refractory solid tumors.
Highlights
Many efforts were undertaken for a thorough and more profound understanding of cancer diseases to develop potent strategies in prevention, diagnosis, and therapy
We investigated the effects of age, tumor type, and molecular profile on therapy recommendation using a binary logistic regression analysis, which showed that several of these factors had a significant impact on the recommendation rate: tumor type (p = 0.46), expression of p-mTOR (p = 0.011), expression of epidermal growth factor receptor (EGFR) (p = 0.046), and expression of PD-L1 (p = 0.023)
The MONDTI platform for precision medicine is an open, tissue-agnostic and molecular-driven platform that seeks to provide targeted therapy strategies to patients based on the respective molecular profile
Summary
Many efforts were undertaken for a thorough and more profound understanding of cancer diseases to develop potent strategies in prevention, diagnosis, and therapy. There has been an effort to develop targeted agents and to individualize and personalize therapy concepts in many cancer entities. This approach is known as precision medicine. The main rationale of precision medicine is to match a therapeutic agent to its corresponding molecular target, to allow a precise treatment tailored to a specific patient It aims to achieve a better and more sustained response than more generic treatments, without damaging healthy cells and tissues. Several trials already demonstrated the clinical benefit of precision medicine by translating the concept of targeted therapies based on the molecular information of the cancer patients into longer overall survival (OS), higher overall response rate (ORR), and lower treatment-related adverse effects (TRAE) [11,12,13]. We sought to describe the potential, the likelihood, and the gender aspects of targeted therapy recommendations in patients with different types of advanced solid tumors without further standard treatment option
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