Tissue- and liquid-biopsy based NGS profiling in advanced non-small-cell lung cancer in a real-world setting: the IMMINENT study.

Introduction: To date, for all non-small cell lung cancer (NSCLC) cases, it is recommended to test for driver alterations to identify actionable therapeutic targets. In this light, comprehensive genomic profiling (CGP) with next generation sequencing (NGS) has progressively gained increasing importance in clinical practice. Here, with the aim of assessing the distribution and the real-world frequency of gene alterations and their correlation with patient characteristics, we present the outcomes obtained using FoundationOne (F1CDx) and FoundationLiquid CDx (F1L/F1LCDx) NGS-based profiling in a nationwide initiative for advanced NSCLC patients.
Methods: F1CDx (324 genes) was used for tissue samples, and F1L (70 genes) or F1LCDx (324 genes) for liquid biopsy, aiming to explore the real-world occurrence of molecular alterations in aNSCLC and their relationship with patients' characteristics.
Results: Overall, 232 advanced NSCLC patients from 11 Institutions were gathered [median age 63 years; never/former or current smokers 29.3/65.9%; adenocarcinoma/squamous 79.3/12.5%; F1CDx/F1L+F1LCDx 59.5/40.5%]. Alterations were found in 170 different genes. Median number of mutated genes per sample was 4 (IQR 3-6) and 2 (IQR 1-3) in the F1CDx and F1L/F1LCDx cohorts, respectively. TP53 (58%), KRAS (22%), CDKN2A/B (19%), and STK11 (17%) alterations were the most frequently detected. Actionability rates (tier I and II) were comparable: 36.2% F1CDx vs. 34% ctDNA NGS assays (29.5% and 40.9% F1L and F1LCDx, respectively). Alterations in KEAP1 were significantly associated with STK11 and KRAS , so as TP53 with RB1 . Median tumor mutational burden was 6 (IQR 3-10) and was significantly higher in smokers. Median OS from metastatic diagnosis was 23 months (IQR 18.5-19.5) and significantly lower in patients harboring ≥3 gene mutations. Conditional three-year survival probabilities increased over time for patients profiled at initial diagnosis and exceeded those of individuals tested later in their clinical history after 12 months.
Conclusion: This study confirms that NGS-based molecular profiling of aNSCLC on tissue or blood samples offers valuable predictive and prognostic insights.
Competing Interests: MaS declares travel fees from Roche and Sanofi unrelated to the current work. LB declares travel fees from Eli Lilly, Sanofi and Takeda, Advisory Board role from AMGEN, Roche and Takeda, Speaker Honoraria from Amgen and BMS, Research funding from BMS, unrelated to the current work. HS declares advisory board role for BMS, MSD, Roche, Pfizer, Takeda, AstraZeneca, Merck unrelated to the current work. MO declares travel accommodation from Eli Lilly and Advisory Board role/Speaker Honoraria from Astra Zeneca, BMS and MSD, outside the submitted work. ES and SC are employed at Roche. LP is the co-owner and an employee of AdRes, which has received project funding from Roche; outside the submitted work, received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational event from Fresenius Kabi, Janssen Cilag, SINPE; AdRes received grants or contracts from Janssen Cilag, Roche, Novartis, Sanofi, Astellas, Diasorin, Nestlè, Shionogi, Boehringer Ingelheim, GSK, and others, outside the submitted work. CP is employee of Adres. The funder had no role in the data collection and no access to patient level data. UM has received personal fees as consultant and/or speaker bureau from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientific, Eli Lilly, Diaceutics, GSK, Merck and AstraZeneca, Janssen, Diatech, Novartis and Hedera unrelated to the current work. SN reports personal fees as speaker bureau or advisor from Eli Lilly, MSD, Roche, BMS, Takeda, Pfizer, Astra Zeneca and Boehringer Ingelheim, unrelated to the current work. EB received speakers’ and travel fees from MSD, Astra-Zeneca, Celgene, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis, and Roche, institutional research grants from Astra-Zeneca and Roche. SP received honoraria or speakers’ fees from Astra-Zeneca, Eli-Lilly, BMS, MSD, Takeda, Amgen, Novartis, and Roche, unrelated to the current work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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