Abstract 114P
Background
Next-generation sequencing (NGS) allows for comprehensive tumor genomic profiling and has become part of routine practice, but the lack of evidence regarding the clinical applicability of reported alterations makes its value less clear. Our aim was to evaluate the clinical value of NGS testing.
Methods
Retrospective analysis of FoundationOne® NGS results in advanced solid tumors from 06/2021 to 07/2023. Lung cancer was excluded.
Results
53 patients were included for analysis. NGS was performed on primary tumor tissue in 29 (52%) patients, ctDNA in 18 (34%) and metastatic tissue in 9 (16%) patients. The most common malignancies were digestive tract (68%), urologic (9%), gynecological (8%) and breast (6%). 60% of patients had received ≥2 lines of systemic treatment and 91% had ECOG-PS 0-1. In 35 (63%) patients, 1-5 molecular alterations were found and only 2 patients (4%) had no molecular alterations reported. Microsatellite instability was found in 2% of tumors and a high tumor mutation burden (TMB) in 12%. KRAS mutations were detected in 19 tumors (36%), of which 2/3 were colorectal; BRCA, PIK3CA and FGFR mutations were present in 9% of patients each and BRAF in 4%. At least one actionable molecular target (ESCAT tiers I-III) was found in 18 patients (34%). Of these, 6 (11%) actually started molecularly-matched therapy (MMT) (2 of them in the setting of clinical trials) (Table) and 3 of these (6%) demonstrated disease control, with a progression-free survival (PFS) between 20 and 33 months; 6 (11%) died before starting targeted treatment and 1 (2%) had the requested drug refused. Table: 114P
| Primary tumor | Age | Baseline molecular results | Molecular target found | ESCAT tier | Molecularly-matched therapy | Best response | Current status | PFS (months) |
| Ampulloma | 55 | pMMR/MSS | High TMB | IC | Pembrolizumab | PD | Deceased | 2 |
| Cervical | 39 | PD-L1 CPS >1 | High TMB | IC | Pembrolizumab | CR | Alive | 33 |
| Colorectal | 60 | pMMR/MSS; KRAS mutated | High TMB | IC | Atezolizumab (clinical trial) | SD | Alive | 20 |
| Pancreatic | 45 | No germline mutations | BRCA2 | IIIB | Olaparib | NE | Deceased | NE |
| Pancreatic | 41 | No germline mutations | FGFR3 | IIIB | Futibatinib (clinical trial) | PD | Deceased | 3 |
| Vagina | 36 | dMMR/MSI-high; PD-L1 CPS <1 | High TMB; MSI-high | IC | Pembrolizumab | PR | Alive | 23 |
CR: complete response; NE: not evaluated; PD: progressive disease; PR: partial response; SD: stable disease.
Conclusions
Even though the most relevant molecular alterations can be detected with cheaper methods, the use of extended genomic panels may allow for a patient to receive MMT and be included in a clinical trial. Further studies are needed to better select patients and the optimal range of reported genomic alterations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.