ASCO 2015 Highlights and Controversies in advanced Lung Cancer Torino, 11 giugno 2015 Paolo Bironzo AOU S Luigi Gonzaga - Orbassano Scuola di Specializzazione in Oncologia Medica Università di Torino
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
Efficacy of Rociletinib (CO-1686) in Plasma-genotyped T790M-positive NSCLC Patients 243 pts T790M +, 188 pts plasma-genotyped Presented by L.V. Sequist, ASCO 2015
Efficacy of Rociletinib (CO-1686) in Plasma-genotyped T790M-positive NSCLC Patients 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 plasma negative pts and 35% RR in centrally negative T790M pts! Hyperglycemia is mediated by a rociletinib metabolite that inhibits IGFR-1/IR Presented by L.V. Sequist, ASCO 2015
Oncogene Driven LCs: EGFR, a 3rd generation affair 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 45/60 female ; 43/60 Asian 22 (exon 19del) vs 24 (L858R); 5 T790M + 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 1-3% of unselected NSCLCs Primary objective: ORR Secondary objectives: PFS, DoR, OS, safety, tolerability, population PK Presented by B. Johnson, ASCO 2015
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 15 PR, 2 SD, 2 PD (independent review) ORR: 83% DCR 88% Presented by B. Johnson, ASCO 2015
Phase II study of cabozantinib for patients with advanced RET-rearranged lung cancers 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 Presented by A. Drilon, ASCO 2015
Phase II study of cabozantinib for patients with advanced RET-rearranged lung cancers ORR: 38% but no PD mdor: 8 months (5.5-26) Most pts required dose reductions, but dose modifications permit to maintain benefit 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
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 Presented by T. Shukuya ASCO 2015
Small Cell Lung Cancer: checkpoint inhibitors could beat la fauve?
KEYNOTE-029: Phase 1 b Multicohort Study of Pembrolizumab for PD-L1+ Advanced Solid Tumors Presented by P.A. Ott ASCO 2015
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 Nivo ORR: 18% Nivo/Ipi ORR: 32.6% 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
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
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 mos 16.7 vs 18.82 months HR 0.61 (95% CI 0.50-0.75), p<0.0001 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
Thank you for your attention!