Targeted Therapy Recommendations for Therapy Refractory Solid Tumors-Data from the Real-World Precision Medicine Platform MONDTI

Our plain-English summary of Targeted Therapy Recommendations for Therapy Refractory Solid Tumors-Data from the Real-World Precision Medicine Platform MONDTI, by H. Taghizadeh, M. Unseld, M. Spalt, et al (Journal of Personalized Medicine, 2020).

The study

• Authors: H. Taghizadeh, M. Unseld, M. Spalt, R.M. Mader, L. Müllauer, T. Fuereder, M. Raderer, M. Sibilia, M.A. Hoda, S. Aust, S. Polterauer, W. Lamm, R. Bartsch, M. Preusser, K.W. A, G.W. Prager
• Journal: Journal of Personalized Medicine
• Published: 2020;10(4)
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This was a single-center, retrospective analysis of the MONDTI precision medicine platform in Vienna. It covered 554 adults with 17 types of advanced solid tumors that had stopped responding to all standard treatments, profiled from June 2013 to January 2020. Tumor samples underwent gene sequencing and protein staining, and a multidisciplinary team decided whether to recommend a targeted drug. The article does not discuss asbestos. A targeted therapy was recommended for 304 patients (54.9%). Among the 14 patients with mesothelioma, 11 (78.6%) received a recommendation. Among patients with malignant mesothelioma, PDGFRα expression was found in 6 of 9 men and 0 of 6 women (p = 0.017), although these 15 patients outnumber the 14 the article lists elsewhere. Only 97 patients (17.5%) received the targeted treatment. Across the whole cohort, disease was controlled in 34 of 554 (6.1%) and tumors responded in 11 of 554 (2.0%). The authors concluded that precision medicine was feasible, but they described the outcome as relatively poor. They noted the analysis was retrospective and included only patients with tissue samples and good performance status.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-center, real-world, retrospective cohort analysis of a precision medicine platform. The authors state the platform is not a clinical trial.
• Who was studied: 554 patients (279 men, 275 women), all at least 18 years old, with 17 types of advanced, therapy-refractory solid tumors (at least 10 patients per type), profiled at the Medical University of Vienna from June 2013 to January 2020. The group included 14 patients with mesothelioma; the article does not say whether these were pleural or peritoneal.
• Exposure: The article does not study or mention asbestos or any other environmental or occupational exposure. It concerns molecular profiling of tumor tissue (next-generation sequencing, immunohistochemistry, FISH) and the resulting targeted therapy recommendations.
• Main results:
  • Whole cohort: a targeted therapy was recommended for 304 of 554 patients (54.9%).
  • Mesothelioma: 11 of 14 patients (78.6%) received a recommendation, the second-highest rate among the tumor types. Five recommendations were rated intermediate evidence and six low evidence.
  • Mesothelioma patients who received the targeted therapy: stable disease in 1, progressive disease in 3, and 1 died before assessment.
  • After cancers specific to one sex were excluded, recommendations were significantly more frequent for men in the total cohort (p = 0.015).
  • A significant sex difference in recommendation rate was found in squamous cell carcinoma of the head and neck (p = 0.0027) and in malignant mesothelioma (p = 0.008).
  • Malignant mesothelioma: PDGFRα expression was seen in 6 of 9 men versus 0 of 6 women (p = 0.017). These denominators total 15, one more than the 14 mesothelioma patients in Table 2, and the article does not explain the difference.
  • When head and neck cancer and mesothelioma were excluded, the sex differences were no longer significant (p = 0.24).
  • In logistic regression, expression of p-mTOR (p = 0.011), EGFR (p = 0.046) and PD-L1 (p = 0.023) was associated with receiving a recommendation. The authors also list tumor type as significant, but print p = 0.46 for it. Age (p = 0.855) and number of mutations (p = 0.850) were not significantly associated.
  • Of the 304 recommendations, 262 (86.2%) were based mainly on immunohistochemistry.
  • The level of evidence for recommendations was high in 25 (8.2%), intermediate in 99 (32.6%) and low in 171 (56.3%).
  • Only 97 of 554 patients (17.5%) actually received the molecularly guided treatment.
  • Among the 97 treated patients, the disease control rate was 35.1% and the overall response rate was 11.3%. Across the whole cohort, the disease control rate was 6.1% (34/554) and the overall response rate was 2.0% (11/554).
  • The median time from failure of the last standard treatment to the start of targeted therapy was 63 days.
• The authors' conclusion: The authors concluded that precision medicine was feasible and provided the basis for molecular-driven therapy recommendations in these patients. They described the clinical outcome as relatively poor and linked it partly to the long turnaround time, tumor heterogeneity and the low level of evidence behind the recommendations.
• Limitations the authors state:
  • The analysis was retrospective.
  • Selection bias: only patients with available tumor specimens and an ECOG performance status of 0 to 1 were included.
  • Changes within tumors over space and time were not considered. Recommendations were based on one biopsy from one timepoint.
  • The distribution of mutations may be confounded by the use of two different gene panels.

Topics

Medical terms in this study, explained in our Lexicon: Targeted Therapy, Prognosis, Mesothelioma, EGFR, PD-L1.

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