Istituto Toscano Tumori –Livorno, Italy Federico Cappuzzo Istituto Toscano Tumori Ospedale Civile...

Istituto Toscano Tumori –Livorno, Italy

Federico CappuzzoIstituto Toscano Tumori

Ospedale CivileLivorno-Italy

Targeted therapies and immunotherapy

Istituto Toscano Tumori – Livorno, Italy

Studies of EGFR TKIs versus chemotherapy as first-line therapy in EGFRmut+ NSCLC

Study # Treatment RR % PFS OS

mPFS(mos)

HRP-value

mOS (mos) HRP-value

IPASS * 97 111

GefitinibCBDCA + TXL

71.2 47.3

9.5 6.3

0.48<0.0001

21.6 21.9

1.000.99

First SIGNAL * 159150

Gefitinib CDDP+ GEM

84.6 37.5

8.0 6.3

0.540.008

27.2 25.6

1.04NR

WJTOG 3405 88 89

Gefitinib CDDP + TXT

62.1 32.2

9.2 6.3

0.48<0.001

36.0 39.0

1.18NR

NEJ 002 114 114

GefitinibCBDCA + TXL

73.7 30.7

10.4 5.5

0.36<0.001

27.7 26.6

0.890.48

OPTIMAL 82 72

Erlotinib CBDCA + GEM

83.0 36.0

13.1 4.6

0.16<0.0001

22.628.8

1.060.68

EURTAC 8482

Erlotinib Platinum Doublet

54.5 10.5

9.4 5.2

0.34<0.0001

19.3 19.5

1.040.87

ENSURE 110107

Erlotinib CDDP + GEM

68.239.3

11.15.7

0.43<0.0001

NRNR

NRNR

LUX Lung 3 230 115

Afatinib CDDP + PEM

56.0 23.0

11.16.9

0.580.0004

16.6 14.8

1.120.60

LUX Lung 6 242122

Afatinib CDDP + GEM

66.9 23.0

11.0 5.6

0.28<0.0001

22.122.2

0.950.76

* Shown data are restricted to EGFRmut + population

Quesiti clinici con gli EGFR-TKIs

• Posso determinare lo stato mutazionale con un test sul sangue?

• Qual è il miglior inibitore?• Il tipo di mutazione di EGFR è importante?• Cosa fare alla progressione?• Posso potenziare l’efficacia?


Detection of plasma EGFR mutations

EGFR status Baseline Progression

Mutated 31 (72%) 11 (76%)

Wild type 12 (28%) 4 (24%)

Total 43 (100%) 15 (100%)

EGFR status Baseline Progression

Mutated 30 (70%) 11 (73%)

Wild type 13 (30%) 4 (27%)

Total 43 (100%) 15 (100%)

Detection of EGFR mutations by UD-NGS

Detection of EGFR mutations by cobas® test

Sensitivity: 72%Specificity: 100%

Sensitivity: 71%Specificity: 100%

Marchetti, et al. WCLC 2015



Gefitinib versus erlotinib as second line treatment in unselected NSCLC: Phase III trial

Katakami N, et al. ASCO 2014

Non-Inferiority trial

• Stage III-IV Adenocarcinoma

• Evaluable disease• 2° line & after• Age >20 years• No interstitial lung disease

R

Erlotinib 150 mg/die

Gefitinib 250 mg/die

Stratification factors:Gender, PS, Stage, Smoking history, Mutation status,Institution, Prior regimen


Gefitinib versus Erlotinib: PFS according to EGFR status

Katakami N, et al. ASCO 2014

Treatment mPFS (mos) p value

Erlotinib 10.09

0.532Gefitinib 8.90


Erlotinib 2.10

0.221Gefitinib 2.07


Erlotinib 2.53

0.878Gefitinib 2.27

Erlotinib versus gefitinib in patients with EGFR mutations: CTONG0901 study

Primary end-point: mPFS

• Advanced NSCLC

• EGFR Mut+(exon 19 or 21)

• ECOG PS 0–2

(n=256)

Until PD or unacceptable

toxicity

Until PD or unacceptable

toxicity

R

Erlotinib150mg/day

Gefitinib 250mg/day

Yang, et al. WCLC 2015


CTONG0901: efficacy and toxicity

0 5 10 15 20 25

mPFS

mOS

HR=0.81; p=0.108

Time (months)

12.4

10.4

22.920.1

HR=0.84; p=0.250

PFS and OS (any line)

Erlotinib

Gefitinib

10.413.0

Treatment-emergent AEs >10% in either arm

AE, %

Gefitinibn=128

Erlotinibn=128

All grade Grade ≥3 All grade Grade ≥3Rash 63 0 70 2

Cough 30 0 23 0Diarrhoea 19 0 17 0Hand and foot syndrome 13 0 6 0Nail changes 13 0 19 0

Anorexia 12 0 5 0



PFS

OS

CTONG0901: PFS and OS by mutation type

0.1 0.2 0.5 1 2 5 10

Erlotinib Gefitinib

EGFR exon 19 0.79 (0.56–1.13) 1.092EGFR exon 21 0.84 (0.55–1.26) 0.388

EGFR exon 19 0.83 (0.56–1.22) 0.345EGFR exon 21 0.86 (0.55–1.34) 0.497

PFS

OS

Subgroup HR (95% Cl) P



Dacomitinib versus erlotinib in EGFRex19 mut+: PFS and OS (N=78)

PFS OS

Suresh S. Ramalingam et al, WCLC 2015



Afatinib versus chemotherapy: OS by EGFR mutation type

Yang J C-H, et al. Lancet Oncol 2015

Exon 19 Exon 21

Indirect comparison of toxicities reported with gefitinib or erlotinib or afatinib


*Shown data include all patients treated with gefitinibData are reported as percentage of AEs of any grade and, in parenthesis, of grade 3

Landi L , Expert Opin Pharmacother 2014

Erlotinib versus erlotinib+bevacizumab as first-line therapy in EGFRmut+ NSCLC: phase IIR study

Erlotinib 150 mg/day(N=75)

Chemotherapy-naive stage IIIB-IV or postoperative recurrenceNon-squamous NSCLCActivating EGFR mutations• Exon 19 deletion• Exon 21 L858RAge ≥ 20 yearsPS 0-1No brain metastasis

Erlotinib 150mg/day +Bevacizumab 15 mg/kg q3w

(N=77)

1:1R 2-yr treatment period

PD

PD


Primary end-point: PFSSecondary End points: OS, ORR, QoL, symptoms improvement FACT-L scale and safety

Seto T, et al. Lancet Oncol 2014


Seto T, et al. Lancet Oncol 2014

Erlotinib versus erlotinib+bevacizumab as first-line therapy in EGFRmut+ NSCLC: PFS

Erlotinib+bevacizumab as first-line therapy in EGFRmut+ NSCLC: the BELIEF phase II study

Chemotherapy-naive stage IIIB-IV or postoperative recurrenceNon-squamous NSCLCActivating EGFR mutations• Exon 19 deletion• Exon 21 L858R• Brain metastases

allowed

Erlotinib 150mg/day +Bevacizumab 15 mg/kg q3w PD


Primary end-point: PFS

Stahel, et al. ECC 2015

ETOP 2-11 BELIEF: Best % change from baseline in the sum of tumor diameters for targeted lesions

All T790M + T790M -CR 7 (6.4) 3 (8.1) 4 (5.6)PR 76 (69.7) 23 (62.2) 53 (73.6)SD 18 (16.5) 9 (24.3) 9 (12.5)PD 3 (2.8) 0 (0.0) 3 (4.2)NE 5 (4.6) 2 (5.4) 3 (4.2)

Response duration (Median, 95%CI): All : 14.8 m (12.0-NE); T790M+ : NE (14.7-NE); T790M- : 12.0 m (8.2-23.3)

N=97



Events/N Median PFS (95%CI) 12m PFS (95%CI)

All 57/109 13.8 m (10.3-21.3) 56.7% (46.0-66.0)

T790M+ 15/37 16.0 m (13.1-NE) 72.4% (53.4-84.7)T790M- 42/72 10.5 m (9.2-16.2) 49.4% (36.6-61.0)

BELIEF: PFS by T790M mutation



BELIEF: data on context with other studies



Rociletinib and AZD9291 in patients EGFRT790M+


Rociletinib

AZD9291

RR:53%

RR:61%

Sequist L, ASCO 2015

Janne PA, NEJM 2015

PFS with rociletinib or AZD9291 in patients EGFRT790M+


Sequist L, et al. ASCO 2015Goss G. et al, ECC 2015

Rociletinib

AZD9291

Rociletinib and AZD9291 in patients EGFRT790M-


RR:21%

Rociletinib

AZD9291


PFS with AZD9291 according to EGFR T790M status

Janne PA, et al. NEJM 2015

9.6 mos

2.8 mos

PFS with rociletinib: 5.6 months in EGFRT790M-

AZD9291 is distributed to mouse brain to a greater extent than gefitinib, afatinib or

Rociletinib


Ballard P, et al. WCLC 2015


Ballard P, et al. WCLC 2015

(11C) AZD9291is distributed to cynomolgus monkey brain


Treatment-related AEs occurring in patients receiving Rociletinib or AZD9291

Sequist L, et al. NEJM 2015Janne PA, et al. NEJM 2015

Rociletinib

AZD9291

Different mechanisms and different options

Molecular event Therapy option

AZD9291

EGFR Del19+ and EGFR T790M+ and EGFR C797S+ Resistant to ALL EGFR-TKIs

EGFR L858R+ and EGFR T790M+ and EGFR C797S+ Partially sensitive to cetuximab

EGFR del 19+ or L858R+ and EGFR T790M- and EGFR C797S+ Sensitive to gefitinib/afatinib

Rociletinib

EGFR Del19+ or L858R+ and EGFR T790M+ and EGFR L718Q+ or L844V+ Potentially sensitive to AZD9291

EGFR del 19+ or L858R+ and EGFR T790M- and EGFR L718Q+ or L844V+ Sensitive to gefitinib/afatinib


Ercan D et al. Clin Cancer Res 2015Thress KS et al. Nature Med 2015Piotrowska Z et al. Cancer Discov 2015Eberlein CA et al. Cancer res 2015

Take home messages sugli EGFR-TKIs

• La biopsia liquida è un’alternativa che può essere utilizzata nella pratica clinica quando il tessuto tumorale non è disponibile o al momento della progressione

• Gefitinib, erlotinib e afatinib hanno simile efficacia e lievi differenze in termini di effetti collaterali

• Non vi sono dati che dimostrano un diverso effetto o superiorità di un inibitore rispetto ad un altro in relazione al tipo di mutazione di EGFR

• L’associazione erlotinib-bevacizumab promettente ma ad oggi NON raccomandata nella pratica clinica

• Rociletinib e AZD9291 differiscono:– Profilo di efficacia– Tossicità– Capacità di penetrazione a livello del SNC– Meccanismi di resistenza acquisita


Quesiti clinici con gli inibitori di ALK

• Cosa fare in presenza di metastasi cerebrali?• Bisogna ripetere la biopsia del tumore alla

progressione a crizotinib?• Qual’ è oggi la migliore sequenza di

trattamento?• Vi sono differenze in tossicità?• Quali nuove prospettive?


ALK inhibitors: CNS activity

AgentsBrain RR

ReferenceN %

Crizotinib 22 * 18 % Costa, J Clin Oncol 2015

Alectinib 9 55 % Gadgeel, Lancet Oncol 2015

Alectinib 34 58.8 % Barlesi, ECC 2015

Alectinib 16 75 % Shaw, WCLC 2015

Ceritinib 33 39.4 % Mok, #8059 ASCO2015

Ceritinib 17 * 58.8 % Felip, #8060 ASCO2015

PF06463922 14 ** 36 % Shaw, #8018 ASCO2015

AP26113 15 ** 53 % Camidge, #8062 ASCO 2015

*ALKi naïve pts, **including ALKi naïve pts (10-16%)


Alectinib: activity by prior radiation70

60

50

40

30

20

10

0

–10

–30

–40

–50

–60

–70

–80

–90

–100

Su

m o

f lo

ng

es

t d

iam

ete

r,

ma

x.

de

cre

as

e f

rom

ba

se

lin

e (

%)

–20

Patients

Prior CNS Radiation Yes (n=34) No (n=16)

Waterfall plot of patients with measurable CNS disease

Gadgeel, et al. WCLC 2015


• In the overall population, only 17% of patients had CNS PD• Progression in the CNS occurred in 8% of patients without CNS disease at baseline

ALK tyrosine kinase mutations and sensitivity to new anti-ALK agents


Pall Curr Opin 2015


Selection of second-line next generation ALK inhibitors based on ALK mutation status

Crizotinib PD

Alectinib or ceritinib or brigatinib or lorlatinib

Alectinib, brigatinib or lorlatinib

Ceritinib or lorlatinib

Lorlatinib

None

F1174

I1171

G1202R

Bx

ALK inhibitors at crizotinib failure

2L1L

Lorlatinib is a potent and selective, CNS penetrant ALK/ROS1 TKI

Crizotinib PF-06463922

Crizotinib PF-06463922

ALK WT NIH3T3 IC50 (nM) 80 1.5

ALK L1196M NIH3T3 IC50 (nM) 843 21

ROS1-CD74 IC50 (nM) 11 0.24MDR BA/AB 45 1.5

CSF or free brain: free plasma (rodent) – 0.23–0.33

Log D 2.0 2.3 Zou HY, et al. Proc Natl Acad Sci U S A 2015;112:3493 Zou HY, et al. AACR-NCI 2013, poster A277

PF-06463922 Is Active Against All Known ALK and ROS1 Resistance Mutations

PF 0

6463

922

activ

ity


Lorlatinib phase I: response by prior TKI

Bauer, et al. WCLC 2015


R:ROS1 translocated

ALK inhibitors in the crizotinib-failure setting:most common AEs

0

10

20

30

40

50

60

70

80

90

100

15

1

17

0

36

0

30

0

40

1

52

1

20

0

42

4

20

5

15

5

80

6

81

6

29

2

36

6

Perc

enta

ge

Fatigue (grade ≥3/

severe)

Diarrhoea (all grades)

Diarrhoea (grade ≥3/

severe)

Nausea (all grades)

Nausea (grade ≥3/

severe)

Constipation (all grades)

NR

Constipation (grade ≥3/

severe)

Fatigue (all grades)

Brigatinib: pulmonary events• Observed in 13/137 (9%) of patients* who received treatment with brigatinib• Incidence was numerically lower with lower starting doses

*All ALK+ NSCLC patients Barlesi, et al. ECC 2015; Gettinger, et al. WCLC Cortot, et al. ECC 2015; Mok, et al. ASCO 2015

NR NR

Alectinib (NP28673) (n=138)

Brigatinib (n=137)*

Ceritinib ATU (n=208)

Ceritinib (ASCEND-2) (n=140)

NR


Take home messages sugli inibitori di ALK

• Al momento crizotinib è l’agente anti-ALK da utilizzare in prima battuta• Alectinib, brigatinib e ceritinib hanno mostrato efficacia nei pazienti in

progressione a crizotinib.• Alectinib, ceritinib e brigatinib hanno mostrato efficacia nei pazienti con

metastasi cerebrali• La migliore sequenza di trattamento non è definita: identificare il

meccanismo di resistenza può aiutare nel decidere la sequenza da utilizzare

• Il profilo di tossicità di alectinib, ceritinib e brigatinib è differente• Lorlatinib sembra essere efficace in presenza di tutte le mutazioni

secondarie a crizotinib inclusa la G1202R• Lorlatinib sembra essere efficace nei pazienti ROS1 traslocati resistenti a

crizotinib


Quesiti clinici sui checkpoint inhibitors

• Nivolumab è standard terapeutico in seconda linea?– In tutti i pazienti?– Solo negli squamosi?

• Qual è il ruolo predittivo dell’espressione di PDL1?– Vi sono pazienti che possiamo escludere?


CheckMate 017 (NCT01642004) - Study Design

• One pre-planned interim analysis for OS• At time of DBL (December 15, 2014), 199 deaths were reported (86% of deaths required for final analysis)• The boundary for declaring superiority for OS at the pre-planned interim analysis was P <0.03

Patients stratified by region and prior paclitaxel use

Nivolumab3 mg/kg IV Q2W

until PD or unacceptable toxicity

n = 135

Docetaxel75 mg/m2 IV Q3W

until PD or unacceptable toxicity

n = 137

Rand

omiz

e 1:

1

• Primary Endpoint: – OS

• Additional Endpoints: -̶ Investigator-assessed ORR-̶ Investigator-assessed PFS-̶ Correlation between PD-L1 expression and efficacy-̶ Safety-̶ Quality of life (LCSS)

• Stage IIIb/IV SQ NSCLC

• 1 prior platinum doublet-based chemotherapy

• ECOG PS 0–1

• Pre-treatment (archival or fresh) tumor samples required for PD-L1 analysis

N = 272

LCSS = Lung cancer symptom scale

Brahmer J, et al. NEJM 2015


Checkmate 017: updated overall survival


Reckamp, et al. WCLC 2015

CheckMate 057 (NCT01673867) Study Design

• PD-L1 expression measured using the Dako/BMS automated IHC assay14,15

– Fully validated with analytical performance having met all pre-determined acceptance criteria for sensitivity, specificity, precision, and robustness

a Maintenance therapy included pemetrexed, bevacizumab, or erlotinib (not considered a separate line of therapy); b Per RECIST v1.1 criteria as determined by the investigator.

Rand

omiz

e 1:

1

• Stage IIIB/IV non-SQ NSCLC• Pre-treatment (archival or recent) tumor

samples required for PD-L1

• ECOG PS 0–1

• Failed 1 prior platinum doublet

• Prior maintenance therapy alloweda

• Prior TKI therapy allowed for knownALK translocation or EGFR mutation

N = 582

Nivolumab3 mg/kg IV Q2W

until PD orunacceptable toxicity

n = 292

Docetaxel75 mg/m2 IV Q3W

until PD orunacceptable toxicity

n = 290

• Primary Endpoint– OS

• Additional Endpoints– ORRb

– PFSb

– Safety– Efficacy by tumor PD-L1 expression– Quality of life (LCSS)

Patients stratified by prior maintenance therapy and line of therapy (second- vs third-line)

Paz-Ares L, et al. ASCO 2015


Overall Survival

Symbols represent censored observations.

Nivolumab(n = 292)

Docetaxel(n = 290)

mOS, mo 12.2 9.4

HR = 0.73 (96% CI: 0.59, 0.89); P = 0.0015

Nivolumab

Docetaxel

1-yr OS rate = 51%

1-yr OS rate = 39%

292 232 194 169 146 123 62 32 09

290 244 194 150 111 88 34 10 05

Nivolumab

Docetaxel

Number of Patients at Risk

OS

(%)

Time (months)

100

90

80

70

60

50

40

30

10

0

20

27211815129630 24



OS by PD-L1 Expression

mOS (mo)

Nivolumab Docetaxel

PD-L1 ≥1% 9.3 7.2

PD-L1 <1% 8.7 5.9

mOS (mo)

Nivolumab Docetaxel

PD-L1 ≥5% 10 6.4

PD-L1 <5% 8.5 6.1

mOS (mo)

Nivolumab Docetaxel

PD-L1 ≥10% 11 7.1

PD-L1 <10% 8.2 6.1

1% PD-L1 Expression level 5% PD-L1 Expression level 10% PD-L1 Expression level

Nivolumab PD-L1+Nivolumab PD-L1–

Time (months)

24211815129630

Time (months)

24211815129630

Time (months)

24211815129630

100

90

80

70

60

50

40

30

10

0

20

OS

(%)

24211815129630

100

90

80

70

60

50

40

30

10

0

20

Docetaxel PD-L1+ Docetaxel PD-L1– Brahmer J, et al. NEJM 2015


NivoDoc

NivoDoc

100

90

80

70

60

50

40

30

10

0

20

Time (months)

100

90

80

70

60

50

40

30

10

0

20

24211815129630 27

Time (months)

24211815129630 27

Symbols represent censored observations.

OS by PD-L1 Expression

mOS (mo)

Nivo 10.4

Doc 10.1

mOS (mo)

Nivo 17.2

Doc 9.0

mOS (mo)

Nivo 9.9

Doc 10.3

mOS (mo)

Nivo 19.4

Doc 8.0

Time (months)

≥5% PD-L1 expression level

<5% PD-L1 expression level

mOS (mo)

Nivo 18.2

Doc 8.1

mOS (mo)

Nivo 9.7

Doc 10.1


HR (95% CI) = 0.59 (0.43, 0.82)

Time (months)


OS

(%)

HR (95% CI) = 0.90 (0.66, 1.24)

HR (95% CI) = 0.43 (0.30, 0.63)

HR (95% CI) = 1.01 (0.77, 1.34)

OS

(%)

Time (months)

Time (months)



HR (95% CI) = 0.40 (0.26, 0.59)

HR (95% CI) = 1.00 (0.76, 1.31)

24211815129630 27

100

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24211815129630 27

24211815129630 27

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24211815129630 27

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*Phase III dose: 2mg/kg q3w and 10mg/kg q3w

POPLARPhII allcomer 2/3L atezo

vs. doc(n=287)

CheckMate 017PhIII 2L Sq nivo vs. doc

(n=272)

CheckMate 057PhIII 2/3L NSq nivo vs. doc

(n=582)

KEYNOTE-001PhIb (inc. NSCLC) pembro

(n=394 for previously treated)

ORR, % Atezo 15% vs doc 15% Nivo 20% vs doc 9% Nivo 19% vs doc 12% Pembro 18%Notes G3–4 treatment-related

AEs: 12 vs 40%G3–4 treatment-related

AEs: 8 vs 56%Reduction from baseline in lung cancer symptoms with

nivolumab

G3–4 treatment-related AEs: 10 vs 54%

Low incidence of immune-related AEs

Refs. Spira, et al. ASCO 2015Vansteenkiste, et al. ECC 2015

Spigel, et al. ASCO 2015Reckamp, et al. WCLC 2015

Gralla, et al. WCLC 2015Reck, et al. ECC 2015

Paz-Ares, et al. ASCO 2015Horn, et al. ECC 2015

Garon, et al. AACR 2015Soria, et al. ECC 2015

0.0

5.0

10.0

15.012.6

9.7

2.7 3.0

9.2

6.0

3.52.8

12.2

9.4

2.3

4.2

11.3

3.0

Tim

e (

mo

nth

s)

NivoOS

DocOS

PembroOS

PembroPFS

AtezoOS

NivoPFS

DocPFS

NivoOS

DocOS

NivoPFS

DocPFS

DocOS

AtezoPFS

DocPFS

HR 0.59 / 0.62p=0.00025 / p=0.0004

HR 0.63p=0.0008

HR 0.73p=0.0015

HR 0.92p=0.3932

HR 0.73p=0.040

HR 0.94

10mg/kg*q2w and q3w


Checkpoint inhibitors in NSCLC: Data in 2nd/3rd line

Checkpoint inhibitors: efficacy by PD-L1 expression

POPLARPhII all comer 2/3L atezo vs.

doc (n=287)

CheckMate 017PhIII 2L Sq nivo vs. doc

(n=272)

CheckMate 057PhIII 2/3L NSq nivo vs. doc

(n=582)

KEYNOTE-001PhIb (inc. NSCLC) pembro

(n=394 for previously treated)

Refs. Spira, et al. ASCO 2015Vansteenkiste, et al. ECC 2015

Spigel, et al. ASCO 2015Reckamp, et al. WCLC 2015

Gralla, et al. WCLC 2015

Paz-Ares, et al. ASCO 2015Horn, et al. ECC 2015

Garon, et al. AACR 2015Soria, et al. ECC 2015

0

5

10

15

11.4

9.5

2.83.4

9.2

6

3.52.8

12.2

9.4

2.3

4.2

9.3

3

Tim

e (

mo

nth

s)

NivoOS

DocOS

PemOS

PemPFS

AtezoOS

NivoPFS

DocPFS

NivoOS

DocOS

NivoPFS

DocPFS

DocOS

AtezoPFS

DocPFS

HR 0.59p=0.00025

HR 0.62p=0.0004

HR 0.73p=0.0015

HR 0.92p=0.3932

HR 0.77p=0.1071

HR 0.98p=0.8606

Efficacy by PD-L1

status

Improved survival with atezolizumab correlated

with increasing PD-L1 expression

Benefit from nivolumab was independent from PD-L1

expression in squamous NSCLC

PD-L1 expression is predictive of nivolumab benefit in

non-squamous NSCLC

PD-L1 proportion score ≥50% showed greatest benefit from

pembrolizumab

Median OS (months)PD-L1 cut-off ≥50%: 15.5PD-L1 cut-off 1-49%: 7.8PD-L1 cut-off <1%: 8.6

PD-L1 assay

SP142 (Ventana)on ICs and TCs 28-8 (Dako) on TCs 22C3 (Dako) on TCs

≥5% cut-off

<5% cut-off

≥10% cut-off

<10% cut-off

≥1% cut-off

<1% cut-off

ITT

0.59

0.90

0.43

1.01

0.40

1.00

0.73

doc

HR

nivo

0.1 1 2

HRSubgroup

≥5% cut-off

<5% cut-off

≥10% cut-off

<10% cut-off

≥1% cut-off

<1% cut-off

ITT

0.69

0.58

0.53

0.70

0.50

0.70

0.39Not quantifiable

0.63

doc

HR

nivo

0.1 1 2

HRSubgroup

doc

HR

atezo

0.2 1 2

TC1/2/3 or IC1/2/3

TC0 and IC0

TC3 or IC3

TC2/3 or IC2/3

ITT 0.73

0.49

0.54

0.59

1.04

HRSubgroup


Take home messages sui checkpoint inhibtors

• Nivolumab è lo standard terapeutico di seconda linea nei pazienti con NSCLC senza driver (EGFR, ALK e ROS1 negativi) indipendentemente dall’istologia

• Confronti indiretti suggeriscono che pembrolizumab e atezolizumab hanno un’efficacia simile a nivolumab

• PDL1 è un predittore debole di sensibilità a nivolumab • Al momento i dati sono insufficienti per escludere qualsiasi

paziente pretrattato con chemioterapia da un trattamento con checkpoint inhibitors


Istituto Toscano Tumori –Livorno, Italy Federico Cappuzzo Istituto Toscano Tumori Ospedale Civile...

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Transcript of Istituto Toscano Tumori –Livorno, Italy Federico Cappuzzo Istituto Toscano Tumori Ospedale Civile...