Usefulness and real-world outcomes of next generation sequencing testing in patients with cancer: an observational study on the impact of selection based on clinical judgement

BACKGROUND: Next Generation Sequencing (NGS) panels are increasingly used in advanced patients with cancer to guide therapy. There is, however, controversy about when should these panels be used, and about their impact on the clinical course. METHODS: In an observational study of 139 patients with cancer having an NGS test [from January 1st, 2017 to December 30th, 2020, in two hospitals (Hospital Universitario de La Princesa and Hospital Universitario Quironsalud Madrid) from Spain], we evaluated whether the clinical course (progression-free survival, PFS) was influenced by drug-based criteria [druggable alterations, receiving a recommended drug, having a favourable ESCAT category (ESMO Scale for Clinical Actionability of molecular Targets)] or clinical judgement criteria. FINDINGS: In 111 of 139 cases that were successfully profiled, PFS was not significantly influenced by either having druggable alterations [median PFS for patients with druggable alterations was 170 (95% C.I.: 139–200) days compared to 299 (95% C.I.: 114–483) for those without; p = 0.37], receiving a proposed matching agent [median PFS for patients receiving a genomics-informed drug was 195 days (95% C.I.: 144–245), compared with 156 days for those that did not (95% C.I.: 85–226); p = 0.50], or having favourable ESCAT categories [median PFS for patients with ESCAT I-III was 183 days (95% C.I.: 104–261), compared with 180 (95% C.I.:144–215) for patients with ESCAT IV-X; p = 0.87]. In contrast, NGS testing performed within clinical judgement showed a significantly improved PFS [median PFS for patients that were profiled under the recommended scenarios was 319 days (95% C.I.: 0–658), compared to 123 days (95% C.I.: 89–156) in the non-recommended categories; p = 0.0020]. INTERPRETATION: According to our data, real-world outcomes after NGS testing provide evidence of the benefit of clinical judgement in patients with either advanced cancers that routinely need multiple genetic markers, patients with advanced rare cancers, or patients that are screened for molecular clinical trials. By contrast, NGS does not seem to be valuable when performed in cases with a poor PS, rapidly progressing cancer, short expected lifetime, or cases with no standard therapeutic options. FUNDING: RC, NR-L and MQF are recipients of the PMP22/00032 grant, funded by the ISCIII and co-funded by the 10.13039/501100008530European Regional Development Fund (ERDF). The study also received funds from the CRIS Contra el Cancer Foundation.