Il NSCLC

(1)

Alessandro Russo

UOC Oncologia Medica, A.O. Papardo, Messina (Dir. Prof. V. Adamo)

Borsa FSE Dottorato XXXII ciclo Università degli Studi di Messina alessandro-russo@alice.it

III SESSIONE

Highlights in Immunoncologia Il NSCLC

(2)

Outline of my presentation

 What’s new in LA-NSCLC?

 First line ICIs: a new standard of care in selected patients and novel combinations

 New insights into ICIs use in pre-treated pts

 Emerging Challenges:

 Optimal timing & re-treatment;

 Use in special populations: elderly and PS2

 Hyperprogressive disease

 Novel predictive biomarkers

 Conclusions

(3)

Progresses in stage III NSCLC over the past 3 decades:

from palliative to curative-intent treatment in selected pts

0 5 10 15 20 25 30

RT alone [1] CHT + RT [1] Concurrent CHT-RT [2]

CHT-RT 74Gy vs. 60Gy [3]

Cis-Pem + RT vs. Cis-VP16

+ RT [4]

CHT-RT ± Cetuximab [3]

CHT-RT ± Tecemotide

[5]

10

14

18

20,3

26,8

25 25,6 28,7

25 24

22,3

[1]; Auperin A, et al. Ann Oncol 2006 [2] Auperin A, et al. J Clin Oncol 2010; [3] Bradley JD, et al. Lancet Oncol 2015; [4] Senan S, et al. JCO 2016; [5] Butts C, et al. Lancet Oncol 2014

1980s 1990s 2000s 2010s

Palliative

+4% at 2 years.

Curative

Median Overall Survival (months)

No significant

improvements in mOS over the last 10 years in the RTOG0617, Proclaim

and START trials

Experimental arm Control arm

(4)

PACIFIC trial

Paz-Ares L, et al. ESMO 2017; Antonia SJ, et al. NEJM 2017

(5)

Efficacy results [1]

PFS by BICR (Primary Endpoint; ITT)

“...In conclusion, in the PACIFIC study, one of the coprimary end points was met at this planned interim analysis, and this study showed a significant increase in progression-free survival and no new safety signals with durvalumab in patients with

stage III, unresectable NSCLC who had received chemoradiotherapy....”

“... These positive findings in an unselected patient population, irrespective of baseline expression of PD-L1 on tumor cells, suggest that durvalumab may be an effective adjuvant therapy in patients with stage III disease after standard

treatment...”

Antonia SJ, et al. NEJM 2017; Paz-Ares L, et al. ESMO 2017

(6)

Efficacy results [2]

Incidence of new lesions by BICR

Time to Distant Metastasis or Death by

BICR

Median follow-up: 14.5 mos (range 0.2–29.9)

(7)

“...Uncertainty about the potential mechanisms driving the interaction between immunotherapy and chemoradiotherapy warrants further investigation...”

Safety & Conclusions

SAFETY SUMMARY

(8)

Outline of my presentation

 Conclusions

(9)

0 5 10 15 20 25 30 35

7,9

11,5 12,3 12,6 13,9

19,3 21,6

27,3

34,9

OS (MONTHS)

Schiller et al. ECOG 4599 JMBD PARAMOUNT EURTAC IPASS LUX-LUNG 3 & 6

HISTOLOGY-SELECTED MAINTENANCE EGFR-MUTATED

SQUIRE

SqCC

Progresses in the 1st line treatment of

metastatic NSCLC over the past 2 decades

Non-SqCC

KEYNOTE-001*

*PD-L1 ≥50%, 1L Cohort

PD-L1 SELECTED

2002 2017

(10)

0 5 10 15 20 25 30 35

7,9

11,5 12,3 12,6 13,9

19,3 21,6

27,3

34,9

OS (MONTHS)

Schiller et al. ECOG 4599 JMBD PARAMOUNT EURTAC IPASS LUX-LUNG 3 & 6

HISTOLOGY-SELECTED MAINTENANCE EGFR-MUTATED

SQUIRE

SqCC

Progresses in the 1st line treatment of

metastatic NSCLC over the past 2 decades

Non-SqCC

KEYNOTE-001*

*PD-L1 ≥50%, 1L Cohort

PD-L1 SELECTED

2002 2017

(11)

OS DATA OF THE KN-001 TRIAL:

TREATMENT-NAIVE COHORT

Leighl NB, et al. ASCO 2017

ORR: 40.6% (30.9-50.8) CR: 2.0% and PR: 38.6%

SD: 42.6%

Median time to response: 2.1 mos (1.7-9.5)

No evidence of cumulative immune- related toxicities

(12)

KEYNOTE-024: UPDATED DATA

PFS2 useful to:

 Assess the impact of cross- over on OS

 Assess the effects of a therapy on subsequent treatments

Death

Brahmer J, et al. ASCO 2017

(13)

KEYNOTE-024: UPDATED DATA

Brahmer J, et al. ASCO 2017

Pembrolizumab continued to show OS benefit over chemotherapy as 1st line therapy for advanced NSCLC with PD-L1 TPS ≥50%:

 Median OS for pembrolizumab was not reached with a median follow-up of 19 mos;

 Despite an effective crossover rate of 60%, there remained a high degree of separation of the OS curves

(14)

Peters S, et al. JCO 2017

*TC2/3 or IC2/3 = TC or IC ≥5% PD-L1–expressing cells, respectively.

**TC3 or IC3 = TC ≥50% or IC ≥10% PD-L1–expressing cells, respectively

TC3/IC3**

TC2/3 or IC2/3* (ITT population)

Cohort 1: 1L; Cohort 2: 2L; Cohort 3: ≥3L

(15)

Chemo + IO in 1st line: KEYNOTE 021 cohort G

Langer CJ, et al. Lancet Oncol 2016; Borghaei H, et al. ESMO 2017

2016 2017

HR 0.54; p=0.0067

“...Significant improvements in ORR and PFS observed in prior analyses were maintained...”

Median PFS 13.0 vs. 8.9 mos HR 0.53; p=0.010

PFS data

(16)

Chemo + IO in 1st line: KEYNOTE 021 cohort G

HR 0.90 [95% CI 0.42–1.91]

2016 2017

HR 0.59; p=0.03

Langer CJ, et al. Lancet Oncol 2016; Borghaei H, et al. ESMO 2017

“...Incremental OS benefit, though not statistically significant, continued despite high (~75%) crossover rate to anti–PD-1/PD-L1 therapy in the PC alone arm...”

OS data

(17)

Outline of my presentation

 Conclusions

(18)

The evolution of 2

^nd

line treatment in NSCLC in the Immunotherapy era

0 2 4 6 8 10 12 14

7,5

5,7

9

6,7

10,5

12,6 12,2

9,2 10,4

13,8

*non-SqCC pts only

**SqCC pts only

***PDL-1+ >1% (10mg/kg arm)

2000

2017

[1] Shepherd FA, et al. JCO 2000; [2] Fossella FV, et al. JCO 2000; [3] Hanna N, et al. JCO 2005; [4]Scagliotti GV, et al. Oncologist 2009; [5] Shepherd FA, et al. NEJM 2005; [6] Garon EB, et al. Lancet 2014; [7] Reck M, et al. Lancet Oncol 2014; [8] Borghaei H, et al. NEJM 2015; [9] Brahmer J, et al. NEJM 2015; [10]

Herbst RS, et al. Lancet 2016; [11] Rittmeyer A, et al. Lancet 2017.

MEDIAN OS (mos)

(19)

Five-Year Follow-up From the CA209-003 Study

Brahmer J, et al. ACCR 2017

5-Year Estimates of OS^a

CA209-003 5-Year Update: Phase 1 Nivolumab in Advanced NSCLC

4 Median OS (95% CI), mo

Overall (N = 129) 9.9 (7.8, 12.4) 100

80

60

40

20

0

0 1 2 3 4 5 6 7 8

129 49 27 20 17 16 3 1 0

Years No. at Risk

OS (%)

1 y OS, 42%

2 y OS, 24%

3 y OS, 18% 5 y OS, 16%

aThere were 3 deaths between 3 and 5 years, all due to disease progression; 1 surviving patient was censored for OS prior to 5 years (OS: 58.2+ months) “...The estimated 5-yr OS rate with nivolumab was 16%...”

(20)

PD-L1 ≥1% (n = 38)

38 10 8 7 7 7 2 1 0

Years 100

0 1 2 3 4 5 6 7 8

5 y OS, 23%

20 40 60 80

0

5-Year Estimates of OS by PD-L1 Status^a

6

PD-L1 <1% (n = 30)

No. at Risk

OS (%)

0 1 2 3 4 5 6 7 8

Years 20

40 60 80 100

0

5 y OS, 20%

30 13 7 5 4 3 0 0 0

PD-L1 ≥50% (n = 13)

13 5 5 5 5 5 2 1 0

Years 100

0 1 2 3 4 5 6 7 8

0

5 y OS, 43%

20 40 60 80

aPD-L1 status was not evaluable in 61 (47%) of 129 patients; the estimated 5-y OS rate in patients with unknown PD-L1 status was 10%

Five-Year Follow-up From the CA209-003 Study

Brahmer J, et al. ACCR 2017

5-Year Estimates of OS by Histology

5

Non-squamous (n = 74)

74 28 14 10 9 8 0 0 0

Years 1 y OS, 42%

2 y OS, 24%

3 y OS, 17% 5 y OS, 15%

20 40 60 80 100

0 0 1 2 3 4 5 6 7 8

Squamous (n = 54)

No. at Risk

54 20 12 10 8 8 3 1 0

OS (%)

Years 1 y OS, 41%

2 y OS, 24%

3 y OS, 20% 5 y OS, 16%

20 40 60 80 100

0

0 1 2 3 4 5 6 7 8

Characteristic

All Treated Patients (N = 129)

5-Year Survivors

(n = 16) Median age, years (range) 65 (38, 85) 62 (44, 80)

≥65 years, n (%) 66 (51) 6 (38)

Male, n (%) 79 (61) 9 (56)

ECOG PS, n (%)^a 0

1

27 (21) 100 (78)

4 (25) 12 (75) No. of prior systemic

regimens, n (%) 1−2

≥ 3

59 (46) 70 (54)

6 (38) 10 (62) Smoking status, n (%)

Former smoker Current smoker Unknown

16 (12)^b 92 (71) 21 (16)

3 (19)^b 11 (69) 2 (12) Tumor histology, n (%)^c

Squamous Non-squamous

54 (42) 74 (57)

8 (50) 8 (50)

Characteristic

All Treated Patients (N = 129)

5-Year Survivors

(n = 16) EGFR status, n (%)

Not evaluable Evaluable

Mutant Wild-type

61 (47) 68 (53) 13 (19)^d,e

55 (81)^d

9 (56) 7 (44) 2 (29)^d,e

5 (71)^d PD-L1 status, n (%)

Not evaluable Evaluable

<1%

≥1%

≥50%

61 (47) 68 (53) 30 (44)^d 38 (56)^d 13 (19)^d

6 (38) 10 (62) 3 (30)^d 7 (70)^d 5 (50)^d Select TRAEs^fon nivolumab,

n (%) Any grade Grade 3−4

56 (43) 7 (5)

11 (69) 1 (6)

Long-term survivors had diverse baseline characteristics, including:

 Squamous and non-squamous histology

 ≥1% and <1% PD-L1 tumor expression

 1 to 4 prior lines of systemic therapy

The majority of long-term survivors had durable responses to nivolumab, although some had SD or PD as best overall response

(21)

Felip E, et al. ESMO 2017

Three-Year Follow-up From CM-017/057 studies

 Nivolumab continued to demonstrate long-term OS and PFS benefit in patients with advanced SQ and non-SQ NSCLC

 No new safety signals were identified and rates of TRAEs were similar to those seen at 2 years’ minimum follow-up

(22)

Atezolizumab beyond PD:

a subset analysis of the OAK trial

Gandara DR, et al. ASCO 2017

(23)

Outline of my presentation

 Conclusions

(24)

Spigel DR, et al. ESMO 2017

CheckMate 153:

Continuous vs 1-Year Nivolumab

Exploratory endpoints^d: safety/efficacy^e with continuous vs 1-year treatment, efficacy, other (eg, biomarkers, PK) Key eligibility

criteria

• Advanced/ metastatic NSCLC

• ≥1 prior systemic therapy^a

• ECOG PS 0−2

• Treated CNS

metastases allowed Stop nivolumab

Continuous nivolumab

Nivolumab 3 mg/kg IV Q2W Treatment for 1 year^b

R^c

Nivolumab retreatment allowed at PD

Stop nivolumab Continuous nivolumab

1,245 patients treated^a

220 patients on treatment at

1 year

76 had response or SD at randomization^c

87 had response or SD at randomization^d R^b

Efficacy analyses

(25)

Median, months (95% CI)

PFS rate, % 6-

month 1-year Continuous

tx

NR (NR) 80 65

1-year tx^b 10.3 (6.4, 15.2) 69 40

HR: 0.42 (95% CI: 0.25, 0.71)

No. at risk 1-year tx Continuous tx

87 50 43 33 21 16 5 1 0

76 60 53 49 35 22 10 3 0

Time post-randomization (months)

PFS (%)

0 20 40 60 80 100

0 3 6 9 12 15 18 21 24

Spigel DR, et al. ESMO 2017

Median, months (95% CI)

OS rate, % 6-

month 1-year Continuous

tx

NR (NR) 97 88

1-year tx^b 23.2 (23.2, NA) 95 81 HR: 0.63 (95% CI: 0.33, 1.20)

Time post-randomization (months) 0

20 40 60 80 100

OS (%)

0 3 6 9 12 15 18 21 24 27

Median, months (95% CI) Continuous

tx

NR (NR)

1-year tx^b,c 10.6 (4.8, NA) HR: 0.45 (95% CI: 0.24, 0.85)

Median, months (95% CI) Continuous

tx

NR (5.6, NA)

1-year tx^b 9.6 (4.5, 12.6) HR: 0.44 (95% CI: 0.17,

1.09)

CR/PR SD

1-year tx 49 29 26 20 14 11 3 1 0

Continuous tx 53 45 41 39 28 17 7 2 0 No. at risk

0 20 40 60 80 100

PFS (%)

0 3 6 9 12 15 18 21 24

38 21 17 13 7 5 2 0 0

23 15 12 10 7 5 3 1 0

0 20 40 60 80 100

PFS (%)

0 3 6 9 12 15 18 21 24

PFS data OS data

Outcomes according to prior response

 Re-treatment responses not so exciting

 PFS advantage consistent across subgroups (CR/PR vs. SD)

 This is only an exploratory analysis: a randomized trial should address this question

(26)

Re-Treatment after irAEs: a retrospective analysis of the MSKCC

Santini FC, et al. ASCO 2017

 In patients with irAEs that improve, retreatment with anti–PD-L1 therapy resulted in recurrent or new irAEs in 50% of patients

 Among those who were retreated,

hospitalization and early onset of irAE were associated with increased risk of recurrent/new irAE

 The majority of patients who developed

recurrent/new irAE were successfully managed, but 2 deaths occurred (mortality rate 5%).

Limited responses occurred following retreatment

Among those with CR/PR prior to onset of first irAE, PFS and OS were similar in the retreatment and

discontinuation cohorts

Description and severity of irAEs requiring delay/re-retreatment or discontinuation

Re-Treated Discontinued p-value Grade of the 1^st irAE

G1-2 G3-4

24 (63%) 14 (37%)

11 (34%) 21 (66%)

0.01

Type of irAE Colitis Pneumonitis Musculoskeletal

Skin Pancreas

Liver CNS Endocrine

Nephritis Other

7 (18%) 6 (16%) 5 (13%) 5 (13%) 4 (11%) 3 (8%) 2 (5%) 2 (5%) 2 (5%) 2 (6%)

5 (16%) 8 (25%) 1 (3%) 7 (22%)

0 (0%) 5 (16%)

1 (3%) 1 (3%) 2 (6%) 2 (6%)

0.41

Hospitalization 8 (22%) 18 (56%) 0.003

irAE resolved to:

G 0-1 G≥2

37 (97%) 1 (3%)

22 (76%) 7 (24%)

0.007

(27)

Outline of my presentation

 Conclusions

(28)

NIVOLUMAB IN ECOG PS 2/ELDERLY PATIENTS:

THE CHECKMATE 171 TRIAL

Popat S, et al. ESMO 2017

“...Efficacy of nivolumab in patients aged ≥70 years were comparable to that observed in the overall population (median OS: 11.2 mos); median OS in pts

with ECOG PS 2 was 5.4 mos...”

“...The tolerability of nivolumab in patients with ECOG PS 2 and elderly was comparable to the overall population,..”

(29)

Use of Nivolumab in Elderly Patients With Advanced Non-Squamous NSCLC:Results From the Italian Expanded Access Program (EAP)

Maria Rita Migliorino,1 Alain Gelibter,2 Francesco Grossi,3 Daniele Fagnani,4 Paola Bordi,5 Tindara Franchina,6 Daniele Turci,7 Luigi Di Lauro,8 Stefano Cascinu,9 Luana Calabrò,10 Matteo Brighenti,11 Natale Tedde,12 Alessandra Bearz,13 Sabrina Giusti,14

Enrico Vasile,15 Giammarco Surico,16 Giacomo Cartenì,17 Paolo Marchetti,18 Francesco Verderame,19 Barbara Melotti20

Migliorino MR, et al. ESMO 2017

Higher proportion of elderly than CM-

057 trial (15%

vs. 7%) Efficacy similar to that

observed in the overall EAP population (mOS 11.0 mos;

mPFS 3.0 mos) and the CM- 057 trial population (mOS 12.2 mos, mPFS 2.3 mos)

(30)

Outline of my presentation

 Conclusions

(31)

Hyperprogressive Disease (HPD): a new pattern of PD

Ferrara R, et al. ESMO 2017; Champiat S, et al. Clin Cancer Res 2017; kato S, et al. Clin Cancer Res 2017

“...A novel aggressive pattern of hyperprogression exists in a fraction of patients treated with anti-PD- 1/PD-L1 (~9%). This observation raises some concerns about treating elderly patients (>65 years old) with anti-

PD-1/PD-L1 monotherapy and suggests further study of this phenomenon...” (Champiat S, et al. CCR 2017)

“... Here we report that specific genomic alterations may be associated with accelerated progression, i.e., the presence of MDM2 family amplification or EGFR aberrations...” (Kato S, et al. CCR 2017)

(32)

Ferrara R, et al. ESMO 2017

In 36% of 242 advanced NSCLC pts IO accelerated tumor growth, 40 pts (16%) experienced HPD.

HPD correlated with >2 metastatic sites before IO;

HPD is a negative prognostic factor (median OS

HPD pts <3.5months).

(33)

Outline of my presentation

 Conclusions

(34)

Impact of Tumor Mutation Burden on the Efficacy of First- Line Nivolumab in the CheckMate 026: PFS and ORR

15

PFS by Tumor Mutation Burden Subgroup

CheckMate 026 TMB Analysis: Nivolumab in First-line NSCLC

Nivolumab Chemotherapy

47 30 26 21 16 12 4 1

60 42 22 15 9 7 4 1

111 54 30 15 9 7 2 1 1

94 65 37 23 15 12 5 0 0

Nivolumab

n = 47 n = 60 9.7

(5.1, NR)

5.8 (4.2, 8.5) Chemotherapy

Median PFS, months (95% CI)

High TMB

PFS (%)

3 6 9 12 15 18 21

No. at Risk Months

100 90 80 70 60 50 40 30 20 10 0 0

Nivolumab

Chemotherapy

0 3 6 9 12

Months

15 18 21 24

Nivolumab Chemotherapy 100

90 80 70 60 50 40 30 20 10 0

n = 111 n = 94 4.1

(2.8, 5.4)

6.9 (5.5, 8.6) HR = 1.82 (95% CI: 1.30, 2.55)

Nivolumab Chemotherapy

(95% CI)

Median PFS, months

Low/medium TMB

HR = 0.62 (95% CI: 0.38, 1.00)

16

ORR by Tumor Mutation Burden Subgroup

47

28 23 33

0 10 20 30 40 50 60 70 80 90 100

High Low/medium

ORR (%)

TMB Subgroup

Nivolumab Chemotherapy

111 94

47 60

n =

Peters S, et al. AACR 2017

(35)

17

OS by Tumor Mutation Burden Subgroup

n = 111 n = 94 12.7

(9.9, 16.1)

13.2 (9.5, 15.2)

HR = 0.99 (95% CI: 0.71, 1.40) Nivolumab Chemotherapy

(95% CI)

Median OS, months

Low/medium TMB

55% received nivolumab as crossover and/or post-study treatment

1-y OS rate = 54% vs 53%

0 3 6 9 12

Months

15 18 21 24 100

90 80 70 60 50 40 30 20 10 0

111 99 82 69 59 47 28 11 3

94 87 71 60 50 38 21 6 2

27 Nivolumab Chemotherapy

0 1 n = 47 n = 60

18.3 (11.4, NR)

18.8 (11.3, NR)

HR = 1.10 (95% CI: 0.64, 1.88) Nivolumab Chemotherapy

(95% CI)

Median OS, months

68% received nivolumab as crossover and/or post-study treatment

High TMB

0 3 6 9 12

Months

15 18 21 24 No. at Risk

Nivolumab Chemotherapy

OS (%)

100 90 80 70 60 50 40 30 20 10

0 Nivolumab

Chemotherapy

47 41 35 33 30 24 13 4 0

60 56 48 45 36 34 19 9 1

1-y OS rate = 64% vs 60%

“...OS was similar between treatment arms; 68% of patients with high TMB in the chemotherapy arm received nivolumab as crossover and/or post-study treatment...

Impact of Tumor Mutation Burden on the Efficacy of First- Line Nivolumab in the CM-026: OS data

(36)

PFS by TMB Subgroup and PD-L1 Expression

32 24 13 12 7 5 2 1

28 18 9 3 2 2 2 0

53 35 23 13 10 8 3 0

41 30 14 10 5 4 2 0

No. at Risk

High TMB, PD-L1 ≥50%

High TMB, PD-L1 1–49%

Low/medium TMB, PD-L1 1–49%

Low/medium TMB, PD-L1 ≥50%

16 13 10 8 8 6 2 0 0

31 17 16 13 8 6 2 1 0

70 33 18 9 7 5 1 1 1

41 21 12 6 2 2 1 0 0

22

Months 100

75

50

25

0

6 9 18

3

0 12 15 21

Months 100

75

50

25

0

6 9 18

3

PFS (%)

0 12 15 21 24

High TMB, PD-L1 ≥50%

High TMB, PD-L1 1–49%

Low/medium TMB, PD-L1 1–49%

Low/medium TMB, PD-L1 ≥50%

High TMB, PD-L1 1–49%

Low/medium TMB, PD-L1 1–49%

High TMB, PD-L1 ≥50%

Nivolumab Arm Chemotherapy Arm

 TMB level and tumor PD-L1 expression did not appear to be associated

 PFS appeared to be longer in patients with high TMB regardless of PD-L1 status in the nivolumab arm, albeit numbers were small

 Patients with both high TMB and ≥50% PD-L1 expression had the greatest benefit from nivolumab compared with those with one or neither of these factors

Impact of Tumor Mutation Burden and PDL1 on the Efficacy of First-Line Nivolumab in the Check-Mate 026

(37)

bTMB (blood tumor mutation burden) analysis of POPLAR trial: training set

Gandara D, et al. ESMO 2017; Fabrizio DA, et al. ESMO 2017

(38)

“...these exploratory analyses represent the first demonstration of a novel blood-based assay measuring bTMB that may predict atezo clinical efficacy in 2L+ NSCLC...”

Gandara D, et al. ESMO 2017

bTMB (blood tumor mutation burden)

analysis of OAK trial: validation set

(39)

Outline of my presentation

 Conclusions

(40)

Conclusions and open questions

 Is durvalumab a new standard of care in LA-NSCLC after chemo-radiotherapy?

 Immunotherapy in PD-L1+ ≥50% NSCLCs should be better administered first;

 Chemo + IO for whom? KN-189 trial will provide definitive conclusions;

 Continuing nivolumab over 1 year in non-progressing patients is recommended;

 Novel predictive biomarkers beyond PD-L1 IHC expression are eagerly awaited.

(41)

Il NSCLC

Outline of my presentation

PACIFIC trial

Efficacy results [1]

Efficacy results [2]

Safety & Conclusions

Outline of my presentation

Progresses in the 1st line treatment of

metastatic NSCLC over the past 2 decades

Progresses in the 1st line treatment of

metastatic NSCLC over the past 2 decades

OS DATA OF THE KN-001 TRIAL:

TREATMENT-NAIVE COHORT

KEYNOTE-024: UPDATED DATA

KEYNOTE-024: UPDATED DATA

Chemo + IO in 1st line: KEYNOTE 021 cohort G

Chemo + IO in 1st line: KEYNOTE 021 cohort G

Outline of my presentation

The evolution of 2

line treatment in NSCLC in the Immunotherapy era

Five-Year Follow-up From the CA209-003 Study

Five-Year Follow-up From the CA209-003 Study

Three-Year Follow-up From CM-017/057 studies

Atezolizumab beyond PD:

a subset analysis of the OAK trial

Outline of my presentation

CheckMate 153:

Continuous vs 1-Year Nivolumab

Re-Treatment after irAEs: a retrospective analysis of the MSKCC

Outline of my presentation

Outline of my presentation

Hyperprogressive Disease (HPD): a new pattern of PD

In 36% of 242 advanced NSCLC pts IO accelerated tumor growth, 40 pts (16%) experienced HPD.

HPD correlated with >2 metastatic sites before IO;

HPD is a negative prognostic factor (median OS

HPD pts <3.5months).

Outline of my presentation

bTMB (blood tumor mutation burden) analysis of POPLAR trial: training set

bTMB (blood tumor mutation burden)

analysis of OAK trial: validation set

Outline of my presentation

Conclusions and open questions

Grazie!