Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group

Abstract

Next-generation sequencing (NGS) allows sequencing of a high number of nucleotides in a short time frame at an affordable cost. While this technology has been widely implemented, there are no recommendations from scientific societies about its use in oncology practice. The European Society for Medical Oncology (ESMO) is proposing three levels of recommendations for the use of NGS. Based on the current evidence, ESMO recommends routine use of NGS on tumour samples in advanced non-squamous non-small-cell lung cancer (NSCLC), prostate cancers, ovarian cancers and cholangiocarcinoma. In these tumours, large multigene panels could be used if they add acceptable extra cost compared with small panels. In colon cancers, NGS could be an alternative to PCR. In addition, based on the KN158 trial and considering that patients with endometrial and small-cell lung cancers should have broad access to anti-programmed cell death 1 (anti-PD1) antibodies, it is recommended to test tumour mutational burden (TMB) in cervical cancers, well-and moderately-differentiated neuroendocrine tumours, salivary cancers, thyroid cancers and vulvar cancers, as TMB-high predicted response to pembrolizumab in these cancers. Outside the indications of multigene panels, and considering that the use of large panels of genes could lead to few clinically meaningful responders, ESMO acknowledges that a patient and a doctor could decide together to order a large panel of genes, pending no extra cost for the public health care system and if the patient is informed about the low likelihood of benefit. ESMO recommends that the use of off-label drugs matched to genomics is done only if an access programme and a procedure of decision has been developed at the national or regional level. Finally, ESMO recommends that clinical research centres develop multigene sequencing as a tool to screen patients eligible for clinical trials and to accelerate drug development, and prospectively capture the data that could further inform how to optimise the use of this technology.

Targeted Therapy in Advanced and Metastatic Non-Small Cell Lung Cancer. An Update on Treatment of the Most Important Actionable Oncogenic Driver Alterations

“…To detect the increasing number of treatment relevant molecular targets, frontline simultaneous targeted DNA-and RNA-based next generation sequencing (NGS) is most straightforward as a large panel of relevant genes can be tested for mutations, fusions and amplifications in a timely manner [17]. Total nucleic acid isolation in a single procedure from the same tumor starting material is most tissue sparing.…”

Interstitial lung disease associated with capmatinib therapy in a patient with non‐small cell lung cancer harboring a skipping mutation of MET exon 14

“…Indeed, increasing evidence supports the use of MET‐TKIs in patients with NSCLC harboring such mutations 1 . The increasing application of next‐generation sequencing (NGS) to tumor and blood samples has resulted in the relatively frequent identification of MET ex14 mutations in individuals with NSCLC 10–12 . These mutations appear to be more frequent in older adults, with age also being a risk factor for ILD 9,13 .…”

Tumour-Agnostic Therapy for Pancreatic Cancer and Biliary Tract Cancer

“…The cancer panel test introduced in clinical practice has led to the identification of druggable mutations in approximately 10% of the pancreatic cancers and 40% of the biliary tract cancers [15]. Therefore, utilisation of tumour multigene NGS is recommended for the detection of actionable alterations in cholangiocarcinoma [16].…”