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Hyperprogressive Disease upon Immune Checkpoint Blockade: Focus on Non–small Cell Lung Cancer

  • Lung Cancer (H Borghaei, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Describe the controversial aspects of hyperprogressive disease (HPD) definition, mechanisms, and biomarkers.

Recent Findings

Although immune checkpoint inhibitors (ICIs) demonstrated a survival benefit in non–small cell lung cancer (NSCLC), an acceleration of tumor growth during ICI, defined as HPD, was reported in ~ 13–26% of NSCLC patients and correlated with worse survival compared with conventional progression. Different criteria have been used for HPD definition. The main limitation for the use of tumor growth rate and tumor growth kinetics variations is its inapplicability for patients without a pre-baseline imaging or progressing on non-measurable lesions. On the contrary, time to treatment failure and clinical criteria (i.e., worsening of performance status, presence of new lesions, or metastatic spread to different sites) can be useful in the above-mentioned settings but do not consent an assessment of tumor growth before ICI initiation. Several mechanisms of HPD have been proposed so far, involving both adaptive and innate immunity or based on cell-autonomous signals of cancer growth triggered by ICI. The characterization of HPD biomarkers and the identification and validation on large series of one or more mechanistic explanations for the HPD phenomenon are of paramount significance to avoid detrimental immunotherapy in a subgroup of patients and exploit novel therapeutic targets for future immunotherapy combinations.

Summary

HPD occur in a subgroup of NSCLC patients treated with ICI. Several definitions and mechanisms have been proposed and a consensus on HPD criteria and biological bases is currently lacking.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Author information

Authors and Affiliations

  1. Department of Medical Oncology, Thoracic Oncology Unit, Fondazione IRCSS, Istituto Nazionale dei Tumori Milano, Via Giacomo Venezian 1, 20133, Milan, Italy

    Giuseppe Lo Russo, Marina Chiara Garassino & Roberto Ferrara

  2. University Paris-Saclay Institut Gustave Roussy Inserm Biomarqueurs predictifs et nouvelles strategies therapeutiques en oncologie, 94800, Villejuif, France

    Francesco Facchinetti

  3. Medical Oncology Unit, University Hospital of Parma, Parma, Italy

    Marcello Tiseo

Authors
  1. Giuseppe Lo Russo
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  4. Marina Chiara Garassino
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  5. Roberto Ferrara
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Corresponding author

Correspondence to Roberto Ferrara.

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Conflict of Interest

Giuseppe Lo Russo declares travel accommodation and consultancies from Roche, Bristol-Myers Squibb, MSD, and AstraZeneca. Francesco Facchinetti declares editorial activities sponsored by Roche and Bristol-Myers Squibb. Marcello Tiseo declares advisory boards and speakers’ fee for AstraZeneca, Pfizer, Eli Lilly, Bristol-Myers Squibb, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, and Pierre Fabre and has received research grants from AstraZeneca and Boehringer Ingelheim. Marina Chiara Garassino declares personal financial interests with the following organizations: AstraZeneca, MSD International GmbH, Bristol-Myers Squibb, Boehringer Ingelheim Italia S.p.A, Celgene, Eli Lilly, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche, and Takeda; she also declares institutional financial interests with the following organizations: Eli Lilly, MSD, Pfizer (MISP), AstraZeneca, MSD International GmbH, Bristol-Myers Squibb, Boehringer Ingelheim Italia S.p.A, Celgene, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche, Takeda, Tiziana, and Foundation Medicine; she has also received research funding from the following organizations: AIRC, AIFA, Italian Moh, and TRANSCAN. Roberto Ferrara declares having attended advisory board of MSD and having received travel grants from Pfizer.

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Lo Russo, G., Facchinetti, F., Tiseo, M. et al. Hyperprogressive Disease upon Immune Checkpoint Blockade: Focus on Non–small Cell Lung Cancer. Curr Oncol Rep 22, 41 (2020). https://doi.org/10.1007/s11912-020-00908-9

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