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Papel de la quimioterapia en la era de la inmunoterapia
Dr. Oscar Juan VidalHospital Universitari i Politècnic La Fe, Valencia
Chemotherapy for NSCLC:A plateau has been reached
OS by treatment groupstage IV NSCLC
Schiller et al. NEJM 2001
Histological classification for decision making:Cisplatin vs carboplatin meta-analysis
Ardizzoni et al. JCNI 2007
Histological classification for decision making:Benefit of bevacizumab in Non-Squamous
Sandler et al. NEJM 2006
Carboplatin – Paclitaxel (OS)
Cisplatin – Gemcitabine (PFS)
Reck et al. JCO 2009
Histological classification for decision making:Differential effect of pemetrexed in Non-squamous vs squamous
Scagliotti et al. JCO 2008
Overall no difference in PFS or OS
Cis/Pem better than Cis/gem in non-Sq
Cis/pem inferior than cis/gem in non-Sq
Histological classification for decision making:Maintenance pemetrexed in Non-squamous
Paz Ares et al. JCO 2013
Pemetrexed maintenance offers superior OS in non-squamous
NSCLC
PARAMOUNT trial
Molecular profiling of lung adenocarcinomaTargeted therapy demonstrated superior efficacy than chemotherapy
Jordan et al. Cancer Discovery 2017
Immunotherapy in pretreated patients
Nivolumab – CheckMate 017 (PIII)1
2nd Line, squamous, PD-L1 All-ComerNivolumab – CheckMate 057 (PIII)2
2nd Line, non-squamous, PD-L1 All-Comer
Pembrolizumab - Keynote 010 (PII/III)3
2nd+ Line, PD-L1 TPS ≥1%Atezolizumab – OAK (PIII)4
2nd+ Line, PD-L1 All-Comer
1. Borghaei H et al. Poster presentation at ASCO 2016. 9025. 2. Brahmer JR et al. Oral presentation at AACR 2017. CT077. 3. Herbst RS et al. Poster presentation at ASCO 2017. 9090. 4. Rittmeyer A et al. Lancet. 2017;389(10066):255-265.
Immunotherapy in pretreated patients
PDL1 ≥ 50%: 14.9 vs. 17.3 vs. 8.2
HR 0.54, HR 0.50
1. Borghaei H et al. Poster presentation at ASCO 2016. 9025. 2. Brahmer JR et al. Oral presentation at AACR 2017. CT077. 3. Herbst RS et al. Poster presentation at ASCO 2017. 9090. 4. Rittmeyer A et al. Lancet. 2017;389(10066):255-265.
Response according to PD-L1 positivity in LC
Checkmate 017: Nivolumab vs. Docetaxel
Spigel, ASCO 2015
Checkmate 057: Nivolumab vs. Docetaxel
Horn, ESMO 2015
Keynote 01: pembrolizumab OAK: atezolizumab
Gainor, AACR 2015 Barlesi, ESMO 2016
Molecular profiling of lung adenocarcinomaPembrolizumab in 1st line stage IV NSCLC with PD-L1 ≥50%
Reck et al. NEJM 2016
NewtreatmentparadigminNSCLC
PDL1statusMolecular
PD-L1≥50%PD-L1<50%
EGFR ALK ROS1BRAFV600E HER2 NTRK MET
1STLINEPembrolizumab*,#
Platinumbased-CT+/-bevacizumab*#,
Andmaintenance;CBDCA/Pem/Pembr*
Platinumbased-CT+/-necitumumab*,#
Crizotinib*,#Ceritinib@
Entrectinib@
2NDLINE• Nivolumab*#• Atezolizumab*#• Pembrolizumab*#IfPD-L1+• Docetaxel+Ramucirumab*,#
Platinumbased-CT
• Nivolumab*#• Atezolizumab*#• Pembrolizumab*#IfPD-L1+• Docetaxel+Nintedanib#/Ramu*,#
T790M+à Osimertinib*#(ifnotreceivedas1stLine)
T790M–or1stLineOsimertinibà Pem/Platinum
Ceritinib*#Alectinib#*Brigatinib*Lorlatinib*
Afatinib*,#Erlotinib*,#+/-BVZ#
Gefitinib*,#Dacomitinib@Osimertinib@
Crizotinib*,#Ceritinib*#Alectinib#
Dabrafenib+
Trametinib*#
2018:Entrectinib*,#LOXO101*
Trastuzumab@TDM1@…
Crizotinib@
Platinumbased-CT
Squamous Non-Squamous
*FDAapproved#EMAapproved
@Notyetapproved
PD-L1Oncogeneaddiction
50%
Courtesy Jordi Remon. SEOM 2017
New treatment paradigm in NSCLC
Role of chemotherapy in 1st line treatment of advanced NSCLC
2/3 of patients received chemotherapy in first line
Clasificación de los tumores según la infiltración de linfocitos (TILs) y la expresión de PDL1
Teng et al. Cancer Res 2015
Generalidades de Estrategias de combinaciones con inhibidores de checkpoint
Harris SJ et al. Cancer Biol Med 2016
Benefit of anti-PDL1 combined with chemotherapy in mouse models
Randomized phase-2 study of carboplatin and pemetrexed with or without pembrolizumab as 1st line therapy: Keynote-21 Cohort G
Progression Free Survival
Response rate
Borghaei et al. ESMO 2017
KEYNOTE-189: Phase III study of pembrolizumab or placebo plus pemetrexed and platinum as 1st line therapy
Gandhi et la. AACR 2018
KEYNOTE 407: Phase III study of carboplatin-paclitaxel/Nab-paclitaxel with or without pembrolizumab for Squamous NSCLC
Paz-Ares et al. ASCO 2018
IMpower150: OS of Atezolizumab + CT ± Bevacizumab vs CT + Bevacizumab in 1L Non-squamous NSCLC
Socinski et al. ASCO 2018
Impower131: PFS of Atezolizumab + Carboplatin+ Paclitaxel or Nab-paclitaxel vs Carboplatin + Nab-Paclitaxel as 1L Squamous NSCLC
Jotte et al. ASCO 2018
Immunological effects of cancer therapy
Galluzzi et al. Cancer Immunol Res 2016
Chemotherapy modulates tumor immunity by different mechanisms
Emmens et al. Cancer Immunt Res 2015
Chemotherapy and Immunological responses
Chemotherapy
Enhance immune response Reduce immune response
Immune-based mechanism of chemotherapy
Bracci et al. Cancer Death and Diffent 2014
Chemotherapy after immunotherapy
OR = 0.30
Grigg ASCO 2017, Leger ASCO 2017, Schvartsmana Lung Cancer 2017
ORR to 39%. PFS 4.7 months OS 9.0 months
Progression after the next line of therapy (PFS2) in the KEYNOTE 024
Bramer at al. ASCO 2017
Trials combining immune agents with chemotherapy
Tang et al. Ann Oncol 2018
Stage IV NSCLC
Solange Peters ASCO 2018
juan_osc@gva.es
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