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D. Grapsa
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MTE19 - Monitoring of Treatment Outcome in Clinical Trials and in Routine Practice (Ticketed Session) (ID 313)
- Event: WCLC 2016
- Type: Meet the Expert Session (Ticketed Session)
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 07:30 - 08:30, Stolz 1
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MTE19.02 - Monitoring of Treatment Outcome in Clinical Trials and in Routine Practice (ID 6575)
08:00 - 08:30 | Author(s): D. Grapsa
- Abstract
- Presentation
Abstract:
Monitoring of treatment efficacy and treatment-related toxicity –both in the real-world and the clinical trial setting- is a crucial, complex and constantly evolving aspect in the field of modern personalized oncology. The expansion of our lung cancer armamentarium, due to continuous implementation of novel (and costly) targeted and immunotherapeutic agents, along with their companion diagnostics, has inevitably led not only to substantial improvements in clinical outcomes, but also to increasing demands for a more accurate prediction and prevention of toxicities and more robust evaluation of cost-effectiveness. Furthermore, transition to targeted therapies displaying modes of action and biologic behavior vastly distinct to those of traditional cytotoxic agents, has necessitated the need to revisit our concept of what constitutes “tumor response” in lung cancer treatment (and solid tumors in general). Vital issues that need to be urgently -albeit concertedly- addressed include –but are not limited to- the need to adapt response evaluation criteria, monitoring tools and techniques to this rapidly changing landscape of lung cancer treatment and to increase our focus towards a patient-centered standard of care. Monitoring of treatment efficacy using imaging modalities Monitoring of tumor size changes -as evidenced on quantitative imaging modalities such as CT and MRI scans and typically assessed by the unidimensional RECIST criteria- remains the cornerstone of treatment response evaluation and decision-making in oncology practice and a strong surrogate endpoint for overall survival in clinical trials. Limitations of this approach are, nevertheless, significant and increasingly recognized. First, measurement inaccuracies and considerable inter-observer variability should be pointed out. Second, considerable time and cycles of cytotoxic drugs are needed prior to the appearance of any clinically meaningful tumor size changes on standard imaging studies, meaning that a reduction of tumor volume alone may not represent an early indicator of treatment response. Third, antitumor activity of targeted agents, which may not necessarily result in significant tumor size modification, cannot be accurately assessed or predicted with the use of these conventional strategies; multiparametric imaging –evaluating both anatomical and functional parameters of tumors-is thus required for optimal assessment of tumor behavior (stability, progression or regression). Within this context, functional imaging modalities (i.e. dynamic contrast-enhanced MRI, diffusion weighted imaging or FDG-PET and FLT-PET ) with the potential to visualize physiologic changes in the molecular level, have been investigated for their ability to influence decision-making by predicting or monitoring response to molecularly targeted agents or their value as surrogate outcome measures in the trial setting. Notably, FDG-PET is increasingly used for the evaluation of treatment response (mainly with PET response criteria /PERCIST) in lung cancer, while it is generally acknowledged that combined use of both RESIST and PERSIST criteria might lead to increased accuracy of prediction of treatment response in the earlier treatment stages. Evidently, earlier recognition of tolerance to treatment is vital for reduction of unnecessary toxicity and increase of cost-effectiveness. The barriers of complexity, high cost and limited availability, with regard to the above functional imaging techniques, should nevertheless also be emphasized. Evaluation of response to immune checkpoint inhibitors represents an emerging challenge in the field of immuno-oncology; since the specific patterns of tumor response to these agents cannot be accurately described using conventional imaging criteria, immune-related response criteria (irRC) were first defined in 2009, so as to provide a “common language”, enabling the application of a unified assessment of response to immunotherapy. Controversy with regard to the use of bidimensional measurements (according to the WHO criteria) in the irRC nevertheless ensued; immune-related RECIST 1.1 criteria are now increasingly used in clinical studies. Immune-related response evaluation remains to be implemented in routine practice and seems to represent an emerging endpoint in clinical trials. Monitoring of treatment efficacy using non-imaging modalities Monitoring of response to biomarker-driven therapies targeting specific molecular alterations in the lung cancer genome remains a major challenge in the field of personalized oncology, mainly due to shortage of tissue for the performance of genetic profiling of tumors. Liquid biopsies –detecting circulating tumor cells/CTCs and fragments of cell-free circulating tumor DNA/ctDNA- carry much promise for becoming an excellent and non-invasive alternative to tissue-based testing for the identification of genetic mutations with prognostic or therapeutic relevance. As a blood-based biomarker, ctDNA analysis offers the potential of serial investigations at any time point during the course of treatment, and thus of real-time dynamic monitoring of treatment response and early identification of acquired resistance to treatment or even early detection of recurrence (ideally prior to visible tumor size changes on imaging). The first liquid biopsy test approved by the FDA as a companion diagnostic, cobas[®] EGFR Mutation Test v2, is now increasingly used in routine practice for EGFR mutation testing in patients with advanced non-small cell lung cancer, expanding the access of this population to potential disease-modifying treatments. Comprehensive molecular profiling of tumors using next-generation sequencing (NGS) analysis of ctDNA is another major advancement in personalized lung cancer oncology, with tremendous potential for monitoring of dynamic tumor behavior in response to targeted therapy. Other simple and innovative tools for monitoring of treatment response are also being explored. For example, recent data showed that breath analysis using nanoarray technology may represent a quick and patient-friendly monitoring tool for earlier recognition of treatment failure and thus potentially serve as a surrogate marker for response to lung cancer therapy. Monitoring of treatment-related toxicity Subjective toxicity -which cannot be assessed by current toxicity scales- is frequently under-reported in clinical trials, with important negative implications on drug safety evaluations and patient care in general. Recent data highlight the need to improve the current system of toxicity assessment in the trial setting, mainly via implementation of patient-reported outcomes (PROs). Self-reported (and, ideally, real-time) monitoring of toxicity is increasingly investigated in the setting of routine oncology practice as well. As of yet it remains to be firmly established whether this system may significantly contribute to earlier identification and better management of adverse events, improved patient-physician communication and higher quality of life. Suggested reading 1.Nishino M, Hatabu H, Johnson BE, McLoud TC. State of the art: response assessment in lung cancer in the era of genomic medicine. Radiology 2014; 271: 6-27. 2.Bennett CW, Berchem G, Kim YJ, El-Khoury V. Cell-free DNA and next-generation sequencing in the service of personalized medicine for lung cancer. Oncotarget 2016; doi: 10.18632/oncotarget.11717. 3.Nishino M, Giobbie-Hurder A, Gargano M, Suda M, Ramaiya NH, Hodi FS. Developing a common language for tumor response to immunotherapy: immune-related response criteria using unidimensional measurements. Clin Cancer Res 2013; 19: 3936-43. 4.Di Maio M, Basch E, Bryce J, Perrone F. Patient-reported outcomes in the evaluation of toxicity of anticancer treatments. Nat Rev Clin Oncol 2016; 13: 319-25.
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