Abstract 3469
Background
Ipi 10 mg/kg (every 3 weeks for 4 doses) combined with a 3 + 3 dose-escalation design of RT at week 4 (W4) seemed to have antitumor activity in the 19 pts treated in the phase I study Mel-Ipi-Rx from August 2011 to July 2015 (ESMO 2016, 1117P). This ancillary study assesses the impact of ipi + RT on SIAR and TGR variation (ΔTGR) of irradiated (TGRirr) and non-irradiated (TGRnon-irr) lesions.
Methods
Blood samples were collected at baseline (W0), W4 (before 2nd ipi injection) and W6 (after ipi + RT) to phenotype T cells. TGR, defined as an increase in tumor volume during 1 month, was computed for TGRirr, and TGRnon-irr in 2 periods: (i) Reference-TGR (REF-TGR) on W0, and (ii) Experimental-TGR (EXP-TGR) between W0 and 1st evaluation. The ΔTGR between REF-TGR and EXP-TGR was used to assess the treatment (TRT) effect. A negative value reflected a slowdown of disease progression (DP).
Results
Ipi alone was associated with increased effector T cells (TEM), Treg and ICOS+ CD4+ T cells at W4. At W6, only TEM and ICOS+ CD4+ T cells significantly increased, suggesting that RT + ipi could increase activated memory CD4+ T cells rather than Treg cells. CD8+ T cells did not increase at W4 while central memory T cells (TCM) and terminally differentiated (TEMRA) increased between W4 and W6, suggesting that RT + ipi could boost these CD8+ T populations. Increased CD8 from W0 to W4 was significantly correlated to progession-free survival (PFS) (p = 0.0163). Increased CD8 tended to be positively correlated to overall survival (OS) from W0 to W6 (p = 0.0786). Interestingly, a higher effect of RT + ipi seemed to be associated with a deeper ΔTGRnon-irr than ΔTGRirr, although insignificant. The EXP-TGRnon-irr was significantly associated with DP.
Conclusions
RT + ipi was associated with increased CD4+ and CD8+ ICOS+ T cells. Increased CD8+ was significantly associated with PFS. Thus, immune biomarkers may be useful for early response evaluation. The ΔTGRnon-irr lesions could be more important than ΔTGRirr lesions in responding pts and may be related to an abscopal effect. Updated PFS and OS will be presented.
Clinical trial identification
EUDRACT 2010-020317-93 NCT01557114.
Editorial acknowledgement
Legal entity responsible for the study
Eric Deutsch and Caroline Robert are both corresponding authors and contributed equally to the work.
Funding
Has not received any funding.
Disclosure
C. Boutros: Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Speaker Bureau / Expert testimony: Merck. N. Chaput: Research grant / Funding (self): Cytune Pharma; Research grant / Funding (self): BMS; Research grant / Funding (self): Sanofi; Research grant / Funding (institution): GSK; Honoraria (self), Advisory / Consultancy: AstraZeneca. C. Mateus: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck. E. Routier: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pierre Fabre. C. Massard: Honoraria (self), Advisory / Consultancy: AMGEN; Honoraria (self), Advisory / Consultancy: ASTELLAS; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: BeiGene; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Celgene; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Janssen Cilag; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Merck; Non-remunerated activity/ies: AstraZeneca; Non-remunerated activity/ies: Bayer; Non-remunerated activity/ies: BMS; Non-remunerated activity/ies: Johnson and Johnson; Non-remunerated activity/ies: Lilly; Non-remunerated activity/ies: MedImmune; Non-remunerated activity/ies: Merck. C. Caramella: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: MSK; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Amgen. J. Soria: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Astex; Honoraria (self), Advisory / Consultancy: Clovis; Honoraria (self), Advisory / Consultancy: GSK; Honoraria (self), Advisory / Consultancy: GammaMabs; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: Roche/genentech; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy: Takeda; Full / Part-time employment, Full time employee since 2017: MedImmune; Shareholder / Stockholder / Stock options: AstraZeneca; Shareholder / Stockholder / Stock options: Gristso. C. Robert: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: MSD. E. Deutsch: Honoraria (self), Speaker Bureau / Expert testimony: BMS; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Boehringer; Honoraria (self), Advisory / Consultancy: MedImmune; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy: Accuray; Honoraria (self), Speaker Bureau / Expert testimony: MSD. All other authors have declared no conflicts of interest.
Resources from the same session
3664 - Longitudinal changes in cell-free DNA (cfDNA) methylation levels identify early non-responders to treatment in advanced solid tumors
Presenter: Andrew Davis
Session: Poster Display session 3
Resources:
Abstract
3212 - Multigene panel testing results for hereditary breast cancer in 1325 individuals: implications for gene selection and considerations for guidelines.
Presenter: Georgios Tsaousis
Session: Poster Display session 3
Resources:
Abstract
2591 - PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors
Presenter: Julia Quintanilha
Session: Poster Display session 3
Resources:
Abstract
4377 - ERBB2 mRNA as a predictor in HER2-positive (HER2+)/hormone receptor-positive (HR+) metastatic breast cancer (BC) treated with HER2 blockade in combination with endocrine therapy (ET): a retrospective analysis of the ALTERNATIVE and SOLTI-PAMELA trials.
Presenter: Nuria Chic
Session: Poster Display session 3
Resources:
Abstract
3439 - Early on-treatment vs pre-treatment tumor transcriptomes as predictors of response to neoadjuvant therapy for HER2-positive inflammatory breast cancer
Presenter: Sonia Pernas
Session: Poster Display session 3
Resources:
Abstract
2512 - AXL expression predicts poor prognosis and lack of efficacy of anti-angiogenic and anti-epidermal growth factor receptor (EGFR) agents in patients (pts) with RAS wild type (WT) metastatic colorectal cancer (mCRC)
Presenter: Claudia Cardone
Session: Poster Display session 3
Resources:
Abstract
4061 - Prevalence of EGFR mutations and its correlation with Egyptian patients’ human kinetics (PEEK Study)
Presenter: Adel Ibrahim
Session: Poster Display session 3
Resources:
Abstract
2547 - Evaluation of tumor microenvironment identifies immune correlates of response to combination immunotherapy with margetuximab (M) and pembrolizumab (P) in HER2+ gastroesophageal adenocarcinoma (GEA)
Presenter: Sergio Rutella
Session: Poster Display session 3
Resources:
Abstract
4671 - Clinicopathological and molecular criteria assessment for the screening of hypermutated proficient mismatch repair (pMMR) colorectal cancers (CRC) with exonucleasic domain POLE (edPOLE) mutations (mt).
Presenter: Benoit Rousseau
Session: Poster Display session 3
Resources:
Abstract
3862 - Tumor mutation burden and microsatellite instability in colorectal cancer
Presenter: Francesca Fenizia
Session: Poster Display session 3
Resources:
Abstract