sesiÓn i- terapias dirigidas contra diana · mahmoud jco 2011 . ali ann oncol 2014 . ali ann oncol...
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SESIÓN I- TERAPIAS DIRIGIDAS CONTRA DIANA
PAPEL DE LA INMUNOTERAPIA EN EL TRATAMIENTO DEL CÁNCER
Luis de la Cruz Merino Sº Oncología Médica HUVMacarena (Sevilla)
METASTATIC MELANOMA
Mario Sznol ASCO 2014
87% ORR
100% CBR
NON SMALL CELL LUNG CANCER
Nivolumab Docetaxel
Median
OS 9.2 months 6 months
Hazard Ratio 0.59 CI: 0.44, 0.79, p=0.00025]
March 04th 2015 FDA approved nivolumab for the treatment of
patients with metastatic squamous non-small
cell lung cancer with progression on or after
platinum-based chemotherapy.
the answer is in the stroma…..
… WHAT ABOUT BREAST CANCER???
INDEX
T INFILTRATING LYMPHOCYTES IN BREAST CANCER
- PROGNOSTIC AND PREDICTIVE VALUE
- TIL SUBTYPES
IMMUNE BIOMARKERS IN PERIPHERAL BLOOD
FIRST DATA WITH ANTI-PD1/ ANTI-PD-L1
CONCLUDING REMARKS AND FUTURE PERSPECTIVES
Salgado Ann Oncol 2015
Salgado Ann Oncol 2015
% Stromal TILs Evaluated within the tumor borders
Full sections preferred TILs scored as a continuous variable No relevant TIL threshold (by now)
Salgado Ann Oncol 2015
1058 biopsies preNACT
GeparDuo and
GeparTrio trials
Semiquantitative score
Denkert JCO 2010
Denkert JCO 2010
Issa-Nummer PLOS One 2013
Issa-Nummer PLOS One 2013
8 studies NACT (anthras, taxanes)
845 pax multivariate analysis
17 gene modules
Ignatiadis JCO 2012
Adams JCO 2014
Adams JCO 2014
Mahmoud JCO 2011
Ali Ann Oncol 2014
Ali Ann Oncol 2014
Schmidt Radiotherapy and Oncology 2012
Montero Cancer Immunol Immunother 2010
Montero Cancer Immunol Immunother 2010
47 breast cancer pts NACT
Galluzzi L Oncotarget 2014
33% ORR (3/9) 1 CR SAFETY PROFILE 1 G3/4 TOXICITY
GEICAM INVESTIGATOR INITIATED TRIAL- SPONSORED BY MSD
Pembrolizumab and gemcitabine in her2 - advanced breast cancer
Schedule: Gemcitabine+ Pembrolizumab
•Gemcitabine 1250 mg/m2 iv d1-8
•Pembrolizumab 200 mg iv every 3 weeks
+ TRANSLATIONAL STUDY
Main Inclusion Criteria: • Histologic confirmation of invasive breast carcinoma (biopsy of relapsed disease recommended but not mandatory) • Advanced disease not amenable of curative approach • Luminal A/Luminal B her2-ve (ki67>13%)/Triple Negative IHC • Performance Status < or = 2 • Prior treatment with anthracyclines, taxanes capecitabine and two lines of hormone therapy in HR+ disease
CONCLUDING REMARKS
• T Infiltrating Lymphocytes (TIL)
- Prognostic factor: TN and her2+ (especially TCD8+)
- Predictive factor: pCR
- Pathologic criteria to standardize studies and reports
• Immune Biomarkers in peripheral blood
- Treg, MDSC
- Monitoring Responses & Tailoring Tx
• Anti PD1 & PD-L1 promising efficacy in TNBC
• Strong rationale for combinatorial strategies
• Modern immunotherapy new era in cancer treatment (maybe and hopefully also for BC)
LA ORACIÓN DE MAIMÓNIDES
…Haz que sea modesto en todo excepto en el deseo de conocer el arte de mi profesión. No permitas que me ataque el pensamiento de que ya sé bastante. Por el contrario, concédeme la fuerza, la alegría y la ambición de saber más cada día. Pues el arte es inacabable, y la mente del hombre siempre puede crecer….
Moisés Ben-Maimónides, el español Córdoba 1135- Al-Fustat 1204