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Found 1 Presentation For Request "1939P"

Poster Display session

1939P - Potential role of longitudinal plasma next generation sequencing (NGS) in advanced non-small cell lung cancer (aNSCLC) patients (pts) experiencing hyperprogression (HPD) and early death (ED) during treatment with immune checkpoint inhibitors (ICIs)

Presentation Number
1939P
Speakers
  • Laura Bonanno (Padova, Italy)
Date
17.09.2020

Abstract

Background

The introduction of ICIs in clinical practice has revolutionized aNSCLC treatment but a proportion of pts does not benefit from ICIs and could even derive detrimental effects. No predictive markers are currently available for their early detection. Aim of the study was to characterize pts experiencing HPD and ED with plasma NGS to analyze their modification at an early time-point during treatment.

Methods

aNSCLC pts referring to Istituto Oncologico Veneto were prospectively enrolled in MAGIC-1 study: plasma was collected at baseline (T1) and after three/four weeks (w) of treatment, according to treatment schedule (T2). We selected pts experiencing ED and HPD following ICIs and randomly collected two control groups: having progressive disease (not HPD) as best radiological response and achieving clinical benefit. NGS was performed in plasma by using AVENIO ctDNA Expanded kit. Variant allele fraction (VAF) was used for relative quantification of tumor associated genetic alterations in plasma.

Results

From March 2017 to November 2019, 172 aNSCLCs receiving ICIs were enrolled. Median follow-up was 18.6 (IC95%: 9.3-26.8) months (m). Median overall survival (OS) was 12 (IC95%: 9.9-13.5) m. Median immune related PFS was 5.7 (IC95%: 4.9-6.9) m. Five cases matched criteria for HPD and 31 experienced ED; one overlapped. Median OS of HPD pts was 3.8 (95%CI: 3.6-N.A) m versus 12.1 (95%CI: 10.1-14.1) m of non-HPD pts (p:0.01). The presence of liver or brain metastases increased the risk for HPD/ED (OR: 3.01, p:0.026; OR: 3.03, p:0.033). Till now we analyzed plasma NGS results of all HPD pts, five ED pts and seven cases in each control group. At baseline we observed one RET/KIF5B fusion among HPD pts. Mean fold change (VAF T2/T1) was significantly different among the four groups (p:0.008). Mean fold change (VAF T2/T1) was significantly higher for pts experiencing HPD/ED versus control cases (p:0.037).

Conclusions

In our study population longitudinal NGS analysis is able to discriminate pts potentially deriving detrimental effect (HPD, ED) from ICIs by highlighting VAF increase after three/four w of treatment.

Legal entity responsible for the study

Istituto Oncologico Veneto IOV IRCCS.

Funding

Istituto Oncologico Veneto IOV IRCCS.

Disclosure

All authors have declared no conflicts of interest.

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