CtDNA shed as a tool to select immune checkpoint inhibitors (ICPI) with or without chemotherapy for patients (pts) with advanced non–small cell lung cancer (aNSCLC)

Autor: Benjamin Besse, Russell Madison, Cheryl D. Cho-Phan, Jeremy Snider, Tamara Snow, Filippo Gustavo Dall'Olio, Khaled A. Tolba, Alexa Betzig Schrock, Geoffrey R. Oxnard
Rok vydání: 2022
Předmět:
Zdroj: Journal of Clinical Oncology. 40:9045-9045
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2022.40.16_suppl.9045
Popis: 9045 Background: ICPI are compelling therapies for pts with aNSCLC given the potential for durable benefit and limited toxicity. Even in tumors with biomarkers associated with ICPI response, early progression (eP) can be seen, leading to chemotherapy combination approaches. We hypothesize that ctDNA tumor fraction (TF) may identify pts at risk of eP on ICPI, helping to select the optimal first-line regimen. Methods: This study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine NSCLC clinico-genomic database (FH-FMI CGDB). The de-identified data originated from ~280 US cancer clinics (~800 sites of care). Real-world overall survival (rwOS) accounting for delayed entry and real-world progression free survival (rwPFS) were estimated with Kaplan-Meier analysis. Hazard ratios (HR) were calculated using multivariate Cox proportional hazard models adjusting for relevant covariates. TF was calculated using an aneuploidy-based measure plus variant-based estimate and was categorized as follows: ≥10%: elevated, 1-10%: intermediate, < 1%: low. eP was defined as rw progression within 8 weeks of starting therapy. Results: 426 pts with documented aNSCLC initiated 1st or 2nd line ICPI (128 ICPI, 298 ICPI+chemo) within 60 days of liquid biopsy. 88 (21%) pts had elevated TF, 193 (45%) had intermediate, and 145 (34%) had low. Pts with elevated TF had higher frequency of liver involvement (elevated: 27%; intermediate: 12%; low: 8%) and had worse performance status (ECOG 2+) near the start of therapy (elevated: 33%; intermediate 22%; low: 17%). PD-L1 was unknown for most pts (elevated: 44%; intermediate: 53%; low: 57%); elevated TF was associated with high PD-L1 positivity (elevated: 22%; intermediate: 17%; low: 12%). In pts with elevated TF, eP was more frequent (elevated: 26%, intermediate: 22%, low: 15%). Amongst all patients treated with either ICPI ± chemo, low TF was associated with better median rwPFS (low 6.7m [ref]; intermediate 5.1m, HR: 1.39 [1.11-1.74]; elevated 3.4m, HR: 1.74 [1.31-2.31]) and median rwOS: (low 14.2m [ref]; intermediate 8.4m, HR: 1.52 [1.10-2.09]; elevated 4.6m, HR: 2.17 [1.47-3.21]). In pts with elevated TF, the addition of chemo to ICPI was associated with favorable rwPFS and rwOS compared to pts who received ICPI alone (Table). Conclusions: ctDNA TF identifies pts with aNSCLC with an increased risk of eP on ICPI who may benefit from ICPI+chemo. In pts with low TF, outcomes on ICPI alone are favorable and similar to those receiving ICPI+chemo, suggesting low TF may be a non-invasive tool for identifying pts for single-agent ICPI. [Table: see text]
Databáze: OpenAIRE
Externí odkaz: