Abstract 5162
Background
Rapid progression while on ICIs has been clinically described as HPD, however there is still not a consensus definition for this phenomenon. Institute Gustave Roussy (IGR) firstly described HPD as ≥ two-fold increase in tumor growth rate (TGR) during experimental period (EXP) vs. Reference period (REF). We recently described VHIO HPD using EXP only, as the following: PD at first restaging with ≥40% increase in sum of target lesions or ≥ 20% with appearance of multiple new lesions, with minimum absolute increase in measurable lesions of 10 mm (Matos I. et al. ASCO 2018).
Methods
Patients (pts) treated with ICIs in Ph1 trials at VHIO were analysed (n = 214). Our aim was to assess overall survival (OS) in pts who achieved PD as best response, evaluate HPD according to IGR or VHIO criteria and investigate discordances between both definitions.
Results
From Jan’12 to Oct’17, 214 pts were treated with ICIs (53% in combinations). Best response was PD in 47% pts (n = 101). Only 50 pts were evaluable for the primary endpoint (20 had PD before the first evaluation and 31 had no REF CT-scan). Using IGR criteria, median OS was 4.5 m (95% CI: 3.6-5.3) in HPD group (n = 15) versus 6.3 m (95% CI 1.7-10.9) in non-HPD group (HR = 1.85; 0.86-3.9; p = 0.11). Using VHIO criteria, median OS was 3.6 m (0.8-6.3) in HPD group (n = 21) versus 8.7 m (4.2-13.2) in non-HPD group (HR = 2.33; 1.10-4.95; p = 0.02). Overall concordance rate between the two criteria was 56% (p = 0.45). Most discordances were HPD by VHIO and non-HPD by IGR (28%). Baseline target lesion summatory in EXP was not different in pts with HPD by IGR or VHIO (p > 0.1). Importantly, pts with HPD by IGR had significantly lower TGR-REF (p < 0.001). Using VHIO criteria, we found no difference in TGR-REF between HPD vs non-HPD (p = 0.15). However, higher TGR-EXP was found in pts with HPD using VHIO criteria (p < 0.001).
Conclusions
We were able to validate IGR HPD criteria in our cohort, despite substantial loss in evaluable pts due to missing REF CT scans. No concordance was observed between IGR and VHIO HPD definitions. VHIO HPD criteria is strongly prognostic, easy-to-use in the clinic (EXP only) and biologically sound (not affected by small TGR during previous therapy and linked to high TGR during ICI exposure).
Clinical trial identification
Legal entity responsible for the study
Vall d'Hebron Institute Oncology.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
J. Tabernero: Advisory role: Bayer, Boehringer Ingelheim, Genentech/Roche, Lilly, MSD, Merck Serono, Merrimack, Novartis, Peptomyc, Roche Sanofi, Symphogen, Taiho. E. Garralda: Advisory boards: Roche, NeoMed Therapeutics, Ellypses Pharma. All other authors have declared no conflicts of interest.
Resources from the same session
5877 - TCR beta chain convergence defines the tumor infiltrating T cell repertoire of melanoma and non-small cell lung carcinoma.
Presenter: Timothy Looney
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
Resources:
Abstract
3212 - PI3K inhibition and modulation of immune and tumor microenvironment markers by copanlisib in patients with non-Hodgkin's lymphoma or advanced solid tumors
Presenter: Ahmad Awada
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
Resources:
Abstract
3574 - Pan-squamous genomic profiling stratified by anatomic tumor site and viral association
Presenter: Meagan Montesion
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
Resources:
Abstract
4113 - Toward the Standardization of Bioinformatics Methods for the Accurate Assessment of Tumor Mutational Burden (TMB)
Presenter: Han Chang
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
Resources:
Abstract
4468 - Prediction of primary resistance to anti-PD1 therapy (APD1) in 2nd line NSCLC
Presenter: Egbert Smit
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
Resources:
Abstract
4570 - Immunomodulatory germline variation impacts the development of multiple primary melanoma (MPM).
Presenter: Robert Ferguson
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
Resources:
Abstract
1169 - Leukocyte telomere length and recurrence risk after EGFR-TKIs therapy in patients with advanced lung adenocarcinoma
Presenter: Ming Yang
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
Resources:
Abstract
1707 - Gene embedding: a novel machine learning approach to identify gene candidates related to immunotherapy responsiveness
Presenter: Chi Tung Choy
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
Resources:
Abstract
2123 - Common and rare DPYD variants are predictive for 5FU/capecitabine (5FU) toxicity: The MRC COIN and COIN-B trials
Presenter: Ayman Madi
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
Resources:
Abstract
5671 - The landscape of NTRK fusions in Chinese solid tumor patients
Presenter: Qi Ling
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
Resources:
Abstract