metastasi polmonari: trattamento medico - rete · pdf filewhat are we gonna talk? •...
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Paolo Bironzo AOU S Luigi Gonzaga - Orbassano
Scuola di Specializzazione in Oncologia Medica Università di Torino
ASCO 2015Highlights and Controversies…
in advanced Lung Cancer
Torino, 11 giugno 2015
What are we gonna talk?• Oncogene addicted --> new issues,
some confirmations
• Squamous cell lung cancer --> news from the far East?
• Small cell lung cancer --> promises should be kept!
• MPM --> let it be(v)?
Oncogene Driven LCs: EGFR, a 3rd generation affair
3rd
Oncogene Driven LCs: EGFR, a 3rd generation affair
Presented by L.V. Sequist, ASCO 2015
243 pts T790M +, 188 pts plasma-genotyped
Efficacy of Rociletinib (CO-1686) in Plasma-genotyped T790M-positive NSCLC Patients
Presented by L.V. Sequist, ASCO 2015
ORR (all doses): 53%
DCR (all doses): 85%
ORR (all doses): 53%
DCR (all doses): 82%
Presented by L.V. Sequist, ASCO 2015
Efficacy of Rociletinib (CO-1686) in Plasma-genotyped T790M-positive NSCLC Patients
27% RR in tissue negative and 27% RR in tissue negative and plasma negative pts and 35% RR in plasma negative pts and 35% RR in
centrally negative T790M pts!centrally negative T790M pts!
Hyperglycemia is mediated Hyperglycemia is mediated by a rociletinib metabolite by a rociletinib metabolite
that inhibits IGFR-1/IRthat inhibits IGFR-1/IR
Efficacy of Rociletinib (CO-1686) in Plasma-genotyped T790M-positive NSCLC Patients
Presented by L.V. Sequist, ASCO 2015
Oncogene Driven LCs: EGFR, a 3rd generation affair
Presented by S.S. Ramalingam ASCO 2015
45/60 female ; 43/60 Asian 22 (exon 19del) vs 24 (L858R); 5 T790M +
AZD9291, a Mutant-selective EGFR Inhibitor, as First-line Treatment for EGFR Mutation-positive Advanced NSCLC:
Results From a Phase I Expansion Cohort
Presented by S.S. Ramalingam ASCO 2015
AZD9291, a Mutant-selective EGFR Inhibitor, as First-line Treatment for EGFR Mutation-positive Advanced NSCLC:
Results From a Phase I Expansion Cohort
ORR (all doses): 73% (95% CI 60-84)
DCR (all doses): 97% (95% CI 99-100)
75% free of progression at 12 months
(but immature data to estimate PFS)
Presented by S.S. Ramalingam ASCO 2015
AZD9291, a Mutant-selective EGFR Inhibitor, as First-line Treatment for EGFR Mutation-positive Advanced NSCLC:
Results From a Phase I Expansion Cohort
Oncogene Driven LCs: big steps but little populations
Interim results of a phase II study of the BRAF inhibitor dabrafenib in combination with the MEK inhibitor
trametinib in pts with BRAF V600E mutated metastatic NSCLC
Presented by B. Johnson, ASCO 2015
1-3% of unselected NSCLCs
Primary objective: ORR
Secondary objectives: PFS, DoR, OS, safety, tolerability, population PK
Interim results of a phase II study of the BRAF inhibitor dabrafenib in combination with the MEK inhibitor
trametinib in pts with BRAF V600E mutated metastatic NSCLC
Presented by B. Johnson, ASCO 2015
15 PR, 2 SD, 2 PD (independent review)
ORR: 83%
DCR 88%
Phase II study of cabozantinib for patients with
advanced RET-rearranged lung cancers
Presented by A. Drilon, ASCO 2015
• 1-2% of unselected NSCLC pts
• Diagnosis: FISH or NGS
• Cabo 60 mg/daily
• Primary end point: ORR
• Secondary end points: ORR at 12wks, PFS, OS, toxicity
ORR: 38% but no PD
mDoR: 8 months (5.5-26)
Most pts required dose reductions, but dose modifications permit to maintain benefit
Phase II study of cabozantinib for patients with
advanced RET-rearranged lung cancers
Presented by A. Drilon, ASCO 2015
Squamous cell lung cancer: nedaplatin would bring some light?
Randomized phase III study of nedaplatin plus docetaxel (ND) versus cisplatin plus docetaxel (CD) for advanced or relapsed
squamous cell carcinoma of the lung (SqLC): WJOG5208L
Primary end point: OS
Secondary end points:-PFS-RR-AEs
335 Japanese pts randomized (178 vs 177)
Well balanced except for PS (more 0 in Neda vs Cis; 46 vs 37%)
Presented by T. Shukuya ASCO 2015
Presented by T. Shukuya ASCO 2015
Randomized phase III study of nedaplatin plus docetaxel (ND) versus cisplatin plus docetaxel (CD) for advanced or relapsed
squamous cell carcinoma of the lung (SqLC): WJOG5208L
Small Cell Lung Cancer: checkpoint inhibitors could beat “la fauve”?
Presented by P.A. Ott ASCO 2015
KEYNOTE-029: Phase 1 b Multicohort Study of Pembrolizumab for PD-L1+ Advanced Solid Tumors
KEYNOTE-029: Phase 1 b Multicohort Study of Pembrolizumab for PD-L1+ Advanced Solid Tumors
Presented by P.A. Ott ASCO 2015
Small Cell Lung Cancer: checkpoint inhibitors could beat “la fauve”?
Presented by S.J. Antonia ASCO 2015
Phase I/II Study (ChekMate032) of Nivolumab With or Without Ipilimumab for Treatment of Recurrent SCLC
Presented by S.J. Antonia ASCO 2015
Nivo ORR: 18% Nivo/Ipi ORR: 32.6%
Phase I/II Study (ChekMate032) of Nivolumab With or Without Ipilimumab for Treatment of Recurrent SCLC
Presented by S.J. Antonia ASCO 2015
MPM: drawing new (sustainable?) MAPS
Presented by G. Zalcman, ASCO 2015
Bevacizumab 15 mg/kg plus cisplatin-pemetrexed (CP) triplet versus CP doublet in MPM: Results of the IFCT-GFPC 0701 ‘MAPS’
Randomized Phase 3 Trial
448 pts (225 arm A, 223 arm B)
Objectives:• Primary: OS • Secondary: PFS, QOL, biomarkers, pharmacoeconomics
Presented by G. Zalcman, ASCO 2015
mOS 16.7 vs 18.82 months
HR 0.76 (95% CI 0.61-0-94), p=0.0127
Subgroup analysis--> only EORTC poor prognosis didn’t derive benefit
No differences in QOL (LCSS mesothelioma questionnaire)
Presented by G. Zalcman, ASCO 2015
Bevacizumab 15 mg/kg plus cisplatin-pemetrexed (CP) triplet versus CP doublet in MPM: Results of the IFCT-GFPC 0701 ‘MAPS’
Randomized Phase 3 Trial
mPFS 7.48 vs 9.59 months
HR 0.61 (95% CI 0.50-0.75), p<0.0001
Thank you for your attention!