The following article features coverage from the European Society for Medical Oncology 2020 virtual meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Next-generation sequencing (NGS) of longitudinal blood samples identified gene alterations associated with hyperprogression and early death from immune checkpoint inhibition (ICI) among patients with advanced non-small cell lung cancer (NSCLC), according to the results of a prospective study presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

“No reliable biomarkers are currently available for early identification of patients potentially deriving detrimental effects [from ICIs],” Laura Bonnano, MD, of the Istituto Oncologico Veneto IRCCS in Italy, who presented the study, said.

The prospective MAGIC-1 study included 172 patients with advanced NSCLC receiving ICIs. NGS was performed on plasma samples that were collected at baseline and 3 to 4 weeks after treatment initiation. The relative quantification of tumor-associated genetic alterations was assessed using variant allele fraction.

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The median age was 67 years and 64% of patients were male. Nonsquamous histology was present in 85% of patients and 24% had PD-L1–negative tumors. Metastases to the bone were present in 25% of patients, 15% of patients had metastases to the liver, and 13% of patients had metastases to the brain.

During a median follow-up of 18.6 months, the median overall survival (OS) was 12 months and the median immune-related progression-free survival was 5.7 months.

Hyperprogression occurred among 5 patients, 31 cases of early death occurred, and 1 case experienced both events. Hyperprogression or early death were significantly associated with metastasis to the liver (odds ratio [OR], 3.01; 95% CI, 1.18-7.42; P =.026) or brain (OR, 3.03; 95% CI, 1.14-7.76; P =.034).

NGS was used to determine the mean fold change in the variant allele fraction (VAF) from baseline to plasma collection at 3 to 4 weeks. The fold change in VAF was significantly higher for patients who had hyperprogression compared with patients who experienced early death, progressive disease, or control cases (P =.0079). The fold change was also higher among patients with hyperprogression compared with the control group alone (P =.038).

Dr Bonnano concluded that “longitudinal NGS analysis is able to discriminate patients experiencing early death/hyperprogression at early time point during treatment.”

Read more of Cancer Therapy Advisor‘s coverage of the ESMO Virtual Congress 2020 by visiting the conference page.


Bonanno L, Zulato E, Attili I, et al. 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). Presented at: European Society for Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. Abstract 1939P.