Abstract 5465
Background
IPI score (derived neutrophil/(leukocytes minus neutrophils)ratio [dNLR]>3 plus LDH>upper limit normal) is a emerging tool to predict overall survival (OS) with ICIs in different tumor types. HPD has been reported in 15% of pts on ICIs using different criteria, including ours (PD at first restaging with ≥40% increase in sum of target lesions or ≥ 20% with appearance of multiple new lesions; Matos et al, ASCO 2018). We aimed to assess the prognostic value of IPI and the relevance of HPD in pts enrolled in Ph1T with TAs.
Methods
Retrospective analysis of a consecutive cohort of pts treated with experimental TAs at VHIO Ph1T Unit over the last 3 years (we excluded pts in the first dose escalation cohorts of each trial as well as TAs matched to validated biomarkers). Overall survival (OS) was correlated with VHIO HPD criteria and IPI.
Results
In total, 180 pts were treated with TAs (34% FGFR, 26% PI3K, 19% MET, 13% NOTCH, 5% IDH, 3% RAF). In 39% of the cases, TAs were matched to an emerging enrichment molecular alteration. Median age 59y, 58% female, most common tumor types: 20% colorectal, 17% breast, 9% gynecological, 8% biliary tract. Best response was PD in 55%, SD in 41%, PR in 4%. Our HPD criteria was met in 10% of the cases, across all tumor types and targets (highest prevalence in colorectal pts treated with PI3K inhibitors, 5/18, 28%). Median progression-free survival was 1.8 months (m) [95% CI 1.7-2.2], not affected target selected, molecular match or IPI score (p > 0.2). Median OS was 7.9 m [6.7-10], significantly different as per IPI score (IPI0 18 m [7.8-NA]; IPI1 7.7 m [6.5-9.9]; IPI2 2.6 m [1.7-NA]; p < 0.001). Importantly, in pts with PD as best response while on TAs, HPD did not negatively affect OS (p = 0.43).
Conclusions
Our results show that a prognostic score developed in cohorts treated with ICIs also predicts long-term outcome with TAs in Ph1T. HPD criteria can be met with TAs treatment, but the lack of survival impact (different from internal and external cohorts exposed to ICIs) suggests that it is not a relevant clinical finding.
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 boards: Bayer, Boehringer Ingelheim, Genentech/Roche, Lilly, MSD, Merck Serono, Merrimack, Novartis, Peptomyc, Roche, Sanofi, Symphogen and Taiho. E. Garralda: Advisory role: 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