submit to the journals

Large-scale Genomic Testing Facilitates Precision Medicine in Routine Cancer Care

Oncology & Hematology Review, 2018;15(1):Epub ahead of print
Keywords: Precision medicine, next-generation genomic sequencing, cancer treatment, advanced cancer, gene abnormalities
Disclosure: Ricardo H Alvarez has nothing to disclose in relation to this article.
Acknowledgments: Medical writing assistance was provided by Katrina Mountfort of Touch Medical Media, and supported by Touch Medical Media.
Review Process: This is an expert interview and, as such, has not undergone the journal’s standard peer review process.
Authorship: The named author meets the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, takes responsibility for the integrity of the work as a whole, and has given final approval to the version to be published.
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. © The Authors 2018.
Received: November 01, 2018 Published Online: January 28, 2019
Correspondence: Ricardo H Alvarez, Cancer Treatment Centers of America – Atlanta, 600 Celebrate Life Parkway, Newnan, Georgia 30265, US. E: ricardo.alvarez@ctca-hope.com Twitter @rhalvarez1
Support: No funding was received in the publication of this article.

Over the last decade, genomics has become an increasingly important part of cancer care. In some tumor types, such as lung cancer and melanoma, genetic profiling for actionable mutations has become standard clinical practice.1,2 The development of novel targeted molecular therapies together with the increased availability of next-generation genomic sequencing has led to an interest in genomic profiling in routine cancer care.3–6 However, the complexity of next generation sequencing has prevented many laboratories from implementing it on a large scale. Recently, studies have shown that this approach is feasible in large study populations.7–9

In an expert interview, conducted at the European Society for Medical Oncology (ESMO) 2018 Congress, which was held in Munich, Germany, from October 19–23, 2018, Ricardo Alvarez discusses mutational landscape of metastatic cancers discovered from prospective clinical sequencing at a community practice cancer program, and the findings from the data he presented at ESMO 2018.9

Q. What proportion of cancer patients in your institution are receiving drugs matched to mutations in their tumors?

Approximately 39% of all of our patients undergo a next-generation genomic sequencing text. Of these, around one-quarter to one-third are treated with genetic biomarker-directed treatment. This is a substantial proportion considering that this is a new approach of precision medicine.

Q. Could you tell us a little about the data you are presenting from community practices?

These data were collected over 5 years and comprised a total of approximately 8,000 samples from 7,600 patients with advanced cancer.9 DNA alterations were identified in 94% of tumor samples, and of these, 47% were considered clinically relevant. The personalized medicine programs helped the physician to assign patients to individual targeted therapy. This is an important study; all patients assigned to molecular targeted therapy responded better and the personalized medicine program helped the physician to identify clinical trials.

Q. Which tumors are most amenable to this approach?

The majority of patients amenable to personalized therapy with next-generation genomic sequencing are those with breast cancer, lung cancer, colorectal cancer, gynecological cancers and non-primary cancers. For patients with these tumors, we have found actionable mutations in 28–30% of cases. These can be treated effectively with targeted therapies and represent some of the most common cancers.

Q. What are the limitations of this approach?

The first limitation is the cost: not all patients are able to participate in these studies and have access to genomic sequencing. In addition, access to clinical trials is not available for all these mutations therefore we often treat off-label. Obtaining drugs for off-label treatment is an important barrier.

Q. By how much do you expect the proportion of cancer patients receiving matched treatment to rise in the coming years?

It is hard to predict but most large institutes in the US have next-generation sequencing platforms, which they can offer to selected patients. The increasing frequency of matching treatment over time and the availability of immunotherapy and matching with programmed death ligand 1 (PD-L1) status and tumor mutational burden may further increase this population. It is important to remember that, a few years ago, precision medicine was only used in the research setting and now it is available in routine clinical care, and we are seeing increasing numbers of patients taking part. A lot of studies are showing that this approach is highly selective for increased response rates and progression-free survival.

References:
  1. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364:2507–16.
  2. Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Mol Diagn. 2013;15:415–53.
  3. Singh RR, Patel KP, Routbort MJ, et al. Clinical validation of a next-generation sequencing screen for mutational hotspots in 46 cancer-related genes. J Mol Diagn. 2013;15:607–22.
  4. Roychowdhury S, Iyer MK, Robinson DR, et al. Personalized oncology through integrative high-throughput sequencing: a pilot study. Sci Transl Med. 2011;3:111ra21.
  5. Frampton GM, Fichtenholtz A, Otto GA, et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013;31:1023–31.
  6. Simen BB, Yin L, Goswami CP, et al. Validation of a next-generation-sequencing cancer panel for use in the clinical laboratory. Arch Pathol Lab Med. 2015;139:508–17.
  7. Meric-Bernstam F, Brusco L, Shaw K, et al. Feasibility of large-scale genomic testing to facilitate enrollment onto genomically matched clinical trials. J Clin Oncol. 2015;33:2753–62.
  8. Zehir A, Benayed R, Shah RH, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017;23:703–13.
  9. Alvarez RH, Moran A, Meiri E, et al. Mutational landscape of metastatic cancers discovered from prospective clinical sequencing at community practice cancer program. Presented at: European Society for Medical Oncology (ESMO) 2018 Congress, Munich, Germany, October 19–23, 2018.
Keywords: Precision medicine, next-generation genomic sequencing, cancer treatment, advanced cancer, gene abnormalities