Many oncologists and patients believe that precision medicine holds the promise of bypassing the traditional one-size-fits-all approach in oncology, its real-world use is not yet meeting up to its high hopes. On August 24, 2020, the European Society for Medical Oncology (ESMO) released the first recommendations from a scientific society about the use of multigene next-generation sequencing (NGS).1
“These are the first recommendations from a scientific society about the use of NGS. Our intent is that they will unify decision-making about how NGS should be used for patients with metastatic cancer,”2 said Fernanda Mosele, MD, Medical Oncologist, Gustave Roussy, Villejuif, France, in an ESMO press release.
ESMO proposed 3 recommendations for the use of NGS, including (1) routine use of tumor multigene NGS in non–small-cell lung cancer, prostate cancer, ovarian cancer, and cholangiocarcinoma; (2) testing of tumor mutational burden in moderately and well-differentiated neuroendocrine tumors, and cervical, salivary, thyroid, and vulvar cancers; and (3) encouragement of clinical research centers to develop multigene sequencing as a tool to screen patients who are eligible for clinical trials and to accelerate new drug development.
“Our ability to provide precision medicine to patients has greatly improved over the last couple of years, and the pace of change is increasing. We have more targeted drugs and more amenable regulatory pathways. We have now also advanced our knowledge of tissue agnostic biomarkers, which may help clinicians select targeted treatments irrespective of the tumor type,” stated Rodrigo Dienstmann, MD, Principal Investigator, Oncology Data Science Group, Vall d’Hebron Institute of Oncology, Barcelona, Spain, at the 2020 virtual meeting of ESMO.
Before the development of NGS, scientists used the Sanger sequencing method to read DNA sequences. Frederick Sanger developed the first sequencing technique in the 1970s, and it is still widely used today; however, this approach does have limitations. Sanger’s method can only sequence 1 fragment of a gene region at a time, and it has less sensitivity to detect low-frequency genetic variants compared with NGS.
By contrast, NGS technologies allow for sequencing of an entire genome’s DNA and RNA more rapidly and at a lower cost than the Sanger sequencing method.
“The delivery of precision medicine remains restricted by our capability to interpret the genomic alterations and match them with the most appropriate targeted agents or immunotherapies. Currently, access to the most promising anticancer medicines is not often guaranteed to all patients,” Dr Dienstmann said.
The cost of genomic analyses, and the affordability of treatments, are 2 key factors that limit the successful integration of precision medicine into daily routine. The use of NGS or comprehensive molecular analysis of tumors is still very expensive, and, in some countries, is restricted to academic settings or insured patients.
“Clinicians may know that assessing single-gene alterations in a consecutive manner will provide an incomplete answer, but high costs prevent comprehensive analyses from being ordered,” Dr Dienstmann pointed out. He added that “multigene NGS tests have already passed the tipping point for broad utility in some tumor types, such as lung adenocarcinomas, based on efficiency in cost and tissue use.”
“Precision medicine requires a paradigm change in the management of cancer care. Much progress is being made, but we have to think carefully before using this technology in daily practice,” concluded Dr Dienstmann.
To sign up for our newsletter or print publications, please enter your contact information below.
