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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

3718 - Hyperprogression during immuno-checkpoint inhibitors (ICIs): a clinically significant problem?

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Topics

Supportive Care and Symptom Management

Tumour Site

Presenters

Elena Farè

Citation

Annals of Oncology (2018) 29 (suppl_8): viii400-viii441. 10.1093/annonc/mdy288

Authors

E. Farè1, S. Sdao2, S. Damian1, S. Cresta1, M. Del Vecchio1, M. Di Bartolomeo1, L.A. Di Guardo1, M. Duca1, A. Indini1, A. Necchi1, M. Niger1, M. Prisciandaro1, G. Procopio1, D. Raggi1, E. Verzoni1, G. Pruneri3, M. Di Nicola1, F.G.M. de Braud1

Author affiliations

  • 1 Medical Oncology 1, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, 20133 - Milan/IT
  • 2 Radiology And Imaging Diagnostics, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 3 Department Of Pathology, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milan/IT
More

Resources

Abstract 3718

Background

ICIs can overcome immune-suppression and activate effective immune responses against cancer cells. Therapy with ICIs have led to a clinically-meaningful extension in overall survival across several solid tumors, being endowed with long term disease control-rate in a part of responding patients (pts). However, an acceleration of the tumor growth rate (TGR) during ICI, defined as hyperprogressive disease (HPD), has been reported in 9-29% of pts. Mechanisms underlying HPD are unknown, yet murine double minute 2 (MDM2) family amplification was found in some of these pts.

Methods

We retrospectively identified a series of 334 pts with miscellaneous advanced solid tumors treated with anti-PD1/PD-L1-containing ICI (mono or combo therapy) at our Institution. Inclusion criteria included imaging assessment at 3 timepoints: during reference period (from 3 months to 2 weeks before ICI baseline scan), before ICI therapy start (baseline scan, performed within 28 days) and during ICI treatment. Patients were considered HPD if they showed progressive disease (PD) by RECIST 1.1 at first radiological evaluation and a ≥ 2-fold increase of the TGR during ICI therapy compared to reference period. FISH analysis to evaluate MDM2 family genes amplification was performed in HPD cases whose paraffin embedded tumor material was available.

Results

73 cases were initially excluded from our analysis due to lack of tumor assessment during ICI. Of the remaining pts, 109 reported PD at first evaluation. Of them, only 45 were suitable for the analyses, having all requested radiological examinations available. Seven cases met HPD criteria: 3,5% of evaluable pts (7/197) and 6.4% of all the PD. No correlation with histology, age, serum biomarkers and type of ICI was found. FISH test for MDM2 family has been performed on 3 cases: one case showed amplification MDM4 gene (mean of signals > 8); other cases showed only increased MDM4 ratio score of unknown significance.

Conclusions

Despite the limits of a retrospective analysis and small numbers, in our series HPD is a rare but clinically relevant event. The role of MDM2 family alteration as predictive biomarker is promising and deserves more investigations. Prospective studies including genomic and biological analysis are warranted.

Clinical trial identification

Legal entity responsible for the study

Elena Farè.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

F.G.M. de Braud: Advisor: BMS, Ignyta, MSD, Novartis, Pfizer, Amgen, Roche, Merck Serono, Servier. All other authors have declared no conflicts of interest.

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