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!