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Lung Cancer critical review Silvia Novello [email protected]

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Page 1: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Lung Cancer critical review

Silvia Novello

[email protected]

Page 2: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Lettura personale

Pertanto soggettiva e AMPIAMENTE discutibile (sia nella selezione che nei commenti)

Page 3: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC
Page 4: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Abstract 6504 (Oral Session)

Page 5: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC
Page 6: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC
Page 7: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Chest 2018, article in press

Page 8: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

M Oudkerk,….JK Field, Lancet Oncol 2017

European position statement on lung cancer screening

Page 9: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

COMPLIANCE SCREENING in ITALIA

Page 10: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

• Era/è un «NEED»

• Quale impatto (leggi «ci cambierà la vita»)

ci cambierà la vita

Page 11: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Abstract LBA8501 (Oral Session)

Page 12: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

• Era/è un «NEED»

• Quale impatto

Page 13: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC
Page 14: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC
Page 15: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Advanced NSCLC - First Line – SOC May 2018

Pembrolizumab Gefitinib, Erlotinib, Afatinib

PD-L1>=50% and WT

(25-30%)

Page 16: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Advanced NSCLC - First Line – AFTER AACR 2018

Pembrolizumab Gefitinib, Erlotinib, Afatinib

Page 17: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC
Page 18: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

• Era/è un «NEED»

• Quale impatto

Page 19: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

• La Rivalsa del tanto bistrattato PDL1

Page 20: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

KEYNOTE-407: PFS by PD-L1 tumor proportion scorea

Page 21: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

IMpower131: Investigator-assessed PFS in PD-L1 subgroups (Arm B vs Arm C)

Jotte RM, et al. ASCO 2018. Abstract LBA9000.

Page 22: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

KEYNOTE-042: Overall survival by PD-L1 TPS

Page 23: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

• La Rivalsa del tanto bistrattato PDL1

• ……e la presa di coscienza della necessità di integrare PIU’ marcatori

Page 24: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Gandhi L, Discussant Plenary ASCO 2018

Page 25: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

CheckMate 227: PFS of Nivolumab + Chemotherapy and Nivolumab + Ipilimumab By TMB

Borghaei H, et al. ASCO 2018. Abstract 9001.

Page 26: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Smoking Status, TMB & PD-L1

Gainor JF, et al. ASCO 2018. Abstract 9011.

Page 27: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Clinical and molecular features predicting long-term response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Rizvi H, et al. ASCO 2018. Abstract 9022.

Key message: • This nicely done study documents the

factors affecting long-term response/survival • TMB seemed one of the best predictors • It is a retrospective analysis and subject to

bias

• Responders with LTR vs STR: Depth of response, but not tumor burden, correlated with LTR

– Greater proportion of patients with BOR <−50% and <−80% in LTR

• Baseline tumor burden in patients with LTR is similar to those with STR

LTR STR 0

50

Bas

elin

e tu

mo

r b

urd

en

(mm

)

200 p=0.65

150

100

STR LTR

−75

Ch

ange

in t

um

or

bu

rden

(%

) 0

−25

−50

−100

66% LTR 42% STR

28% LTR 4% STR

Page 28: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Gandhi L, Discussant Plenary ASCO 2018

Page 29: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Kurt Schalper, Yale, ASCO 2018

Tumor Tissue Biomarkers

Page 30: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Kurt Schalper, Yale, ASCO 2018

Circulating Biomarkers

Page 31: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

• La Rivalsa del tanto bistrattato PDL1

• ……e la consapevolezza della necessità di integrare PIU’ biomarcatori

• La caduta di un «mito»

Page 32: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

• La Rivalsa del tanto bistrattato PDL1

• ……e la consapevolezza della necessità di integrare PIU’ biomarcatori

• La caduta di un «mito»

• «On a remis l’église au milieu du village» (liquid biopsy)

Page 33: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC
Page 34: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC
Page 35: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

• La Rivalsa del tanto bistrattato PDL1

• ……e la consapevolezza della necessità di integrare PIU’ biomarcatori

• La caduta di un «mito»

• «On a remis l’église au milieu du village» (liquid biopsy)

• Another piece of pie?

Page 36: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Hiley Lancet 2016

NSCLC Molecular Classification

Page 37: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

Mazieres J, et al. ASCO 2018. Abstract 9010.

Felip E, et al. ASCO 2018. Abstract 9016.

Page 38: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

• La Rivalsa del tanto bistrattato PDL1

• ……e la consapevolezza della necessità di integrare PIU’ biomarcatori

• La caduta di un «mito»

• «On a remis l’église au milieu du village» (liquid biopsy)

• Another piece of pie?

• Quel «figlio» che ci da’ solo delusioni…….

Page 39: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC

DLL3-high n=238 (70%)

Eligible DLL3-Positive Patients

n=101 (30%)

Primary endpoint All dosed (N=339)

DLL3-High

Orr2: Investigator, % 95% CI

18.0 (14.1, 22.5)

19.7 (14.9, 25.4)

ORR2: IRC, % (95% CI)

12.4 (9.1, 16.4)

14.3 (10.1, 19.4)

Median OS, Mo (95% CI)

5.6 (4.9, 6.1)

5.7 (4.9, 6.7)

Page 40: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC
Page 41: Lung Cancer critical review - AIOMmedia.aiom.it/userfiles/files/doc/AIOM-Servizi/slide/20180615MI_13_Novello.pdf · response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC