Are We Closer to a Cure With Perioperative Immunotherapy in Resectable NSCLC? Latest Evidence, Current Conclusions, and Ongoing Questions in Clinical Care
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Sep 25, 2024
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About This Presentation
Chair Prof. Solange Peters, MD, PhD, discusses NSCLC in this CME activity titled “Are We Closer to a Cure With Perioperative Immunotherapy in Resectable NSCLC? Latest Evidence, Current Conclusions, and Ongoing Questions in Clinical Care.” For the full presentation, downloadable Practice Aids, an...
Slide Content
Are We Closer to a Cure With Perioperative
Immunotherapy in Resectable NSCLC?
Latest Evidence, Current Conclusions, and
Ongoing Questions in Clinical Care
Prof. Solange Peters, MD, PhD
Chair and Professor, Medical Oncology
Full Professor
University Hospital of Lausanne
| Lausanne, Switzerland
Go online to access full CME information, including faculty disclosures.
Copyright © 2000-2024, PeerView
Immunotherapy in Resectable NSCLC?
Latest Evidence, Current Conclusions, and
Ongoing Questions in Clinical Care
Prof. Solange Peters, MD, PhD
Chair and Professor, Medical Oncology
Full Professor
University Hospital of Lausanne
| Lausanne, Switzerland
Go online to access full CME information, including faculty disclosures.
Copyright © 2000-2024, PeerView
Our Goals for Today
Augment your knowledge of the latest data on
immunotherapy in resectable NSCLC
Improve your ability to interpret clinical evidence supporting
the use of different immunotherapy approaches to personalise
the management of resectable NSCLC.
Equip you with skills for devising individualised care plans
inclusive of immunotherapy to optimise outcomes for patients
with resectable NSCLC
Copyright © 2000-2
Augment your knowledge of the latest data on
immunotherapy in resectable NSCLC
Improve your ability to interpret clinical evidence supporting
the use of different immunotherapy approaches to personalise
the management of resectable NSCLC.
Equip you with skills for devising individualised care plans
inclusive of immunotherapy to optimise outcomes for patients
with resectable NSCLC
Copyright © 2000-2
IMMUNOTHERAPY IN RESECTABLE NSCLC | OUTLINE
PART 1
PART 2
Shining a Light on the Clinical Data
Supporting the Use of Adjuvant,
Neoadjuvant, and Perioperative
Immunotherapy in Resectable NSCLC
Closer to a Cure or Added Clinical
Complexity? Making Sense of the
Innovations for Immunotherapy in
Resectable NSCLC
Copyright © 200
4, PeerView
PART 1
PART 2
Shining a Light on the Clinical Data
Supporting the Use of Adjuvant,
Neoadjuvant, and Perioperative
Immunotherapy in Resectable NSCLC
Closer to a Cure or Added Clinical
Complexity? Making Sense of the
Innovations for Immunotherapy in
Resectable NSCLC
Copyright © 200
4, PeerView
Resectable L Cancer: Poor Prognosis’
= Stage IB: 71%
Stage IIA: 64%
~ Stage IIB: 55%
~~ Stage IIIA: 37%
0 6 12 18 24 30 36 42 48 54 60 66 72
Time, mo
+ According lo St Eton a THM Staging of Lung Cancer. ,
Y GhanseyK etal u Tome Oncol 201211001121. PeerView
PeerView.com/AWU827 Copyright © 2000-2024, PeerView
= Stage IB: 71%
Stage IIA: 64%
~ Stage IIB: 55%
~~ Stage IIIA: 37%
0 6 12 18 24 30 36 42 48 54 60 66 72
Time, mo
+ According lo St Eton a THM Staging of Lung Cancer. ,
Y GhanseyK etal u Tome Oncol 201211001121. PeerView
PeerView.com/AWU827 Copyright © 2000-2024, PeerView
Local therapy Rav pee
Surgery .
e Radiation therapy
Systemic therapy ns .
Chemotherapy
Targeted therapy
Immunotherapy
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Surgery .
e Radiation therapy
Systemic therapy ns .
Chemotherapy
Targeted therapy
Immunotherapy
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Adjuvant Neoadjuvant Perioperative
IMpower010 CheckMate -816 KEYNOTE-671
PEARLS/KEYNOTE-091 AEGEAN
Neotorch
CheckMate -77T
RATIONALE-315
ANVIL IMpower030
BR31
ALCHEMIST chemo-1O
MERMAID
PeerView
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IMpower010 CheckMate -816 KEYNOTE-671
PEARLS/KEYNOTE-091 AEGEAN
Neotorch
CheckMate -77T
RATIONALE-315
ANVIL IMpower030
BR31
ALCHEMIST chemo-1O
MERMAID
PeerView
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Overview of Key Immunotherapy Strategies and Trials
16 AEGEAN‘
Timing ‘Aguvant ‘Agjwvant Neoadjuvant. Peñoperaive Perioperative Perlperalve | Petioperalve Perioperative
Size 1.005 1,77 358 802 500 Tor 461 453
a Alezoizumab — Pembrolzumab — NvolumaD DumalumaD Topalmab — PembrolzumaD Niolmab Tiseizumab
Sri (Da) eo) Fon) (Pout) on) Fon) von) on)
cycles, N 15 8 3 15 "7 1 16 2
En en Resectable IB esectable ILE Resectabie ll Resectable IH Resectable ILIIIB/ Resectable INIA.
Ineiuson. Li he ie (24 em} (7th) (eth) by (sth) (8th) (8th) (em)
C4 em Gi) GA emana (7m) lobectomy
Stage Ban % 59/44 72128 36/64 am 20180 30/70 35165 41159
Primary endpoint DFS hierarchical, DES. OFS PCR, EFS pCR, EFS MPR, EFS EFS,OS EFS EFS, MPR
inPD-L1 260%
Platinum doublet patinum dout latinum-base latinum-based Cisplatin doublet latinum doubl latinum doublet
Chemotherapy Cispiain comer MI doublet Plalmumibased Platinumbased Cisplatin doublet Platnum doublet Platinum doublet
No EGFR,
EOFRALK ouced(is%) Indiens) NO | Nodocumenied wr incygeg (7%) no documented WT
mutation, WT Asia mutaton ae
1. Faipe € at al Lancet 2021:98:194-1957.2. Bhan Met al. Lancet One 2022.23274-120 2 Forde P la Eng J Mad 202236 1873-1096.
à Koymach Jet AAGR 2023 Abel TOS, 3 Lu Sta. ASCO 2023 Abstact 81,8 Vakalos Het al Eng! Jed 2023-80 40-202 en
7. Cancone Tet al ESMO 2029. Abstaci LBAT. 8. Yue Dei a ELGG 2028, abstract 1080 PeerView
PeerView.com/AWU827
Copyright © 2000-2024, PeerView
16 AEGEAN‘
Timing ‘Aguvant ‘Agjwvant Neoadjuvant. Peñoperaive Perioperative Perlperalve | Petioperalve Perioperative
Size 1.005 1,77 358 802 500 Tor 461 453
a Alezoizumab — Pembrolzumab — NvolumaD DumalumaD Topalmab — PembrolzumaD Niolmab Tiseizumab
Sri (Da) eo) Fon) (Pout) on) Fon) von) on)
cycles, N 15 8 3 15 "7 1 16 2
En en Resectable IB esectable ILE Resectabie ll Resectable IH Resectable ILIIIB/ Resectable INIA.
Ineiuson. Li he ie (24 em} (7th) (eth) by (sth) (8th) (8th) (em)
C4 em Gi) GA emana (7m) lobectomy
Stage Ban % 59/44 72128 36/64 am 20180 30/70 35165 41159
Primary endpoint DFS hierarchical, DES. OFS PCR, EFS pCR, EFS MPR, EFS EFS,OS EFS EFS, MPR
inPD-L1 260%
Platinum doublet patinum dout latinum-base latinum-based Cisplatin doublet latinum doubl latinum doublet
Chemotherapy Cispiain comer MI doublet Plalmumibased Platinumbased Cisplatin doublet Platnum doublet Platinum doublet
No EGFR,
EOFRALK ouced(is%) Indiens) NO | Nodocumenied wr incygeg (7%) no documented WT
mutation, WT Asia mutaton ae
1. Faipe € at al Lancet 2021:98:194-1957.2. Bhan Met al. Lancet One 2022.23274-120 2 Forde P la Eng J Mad 202236 1873-1096.
à Koymach Jet AAGR 2023 Abel TOS, 3 Lu Sta. ASCO 2023 Abstact 81,8 Vakalos Het al Eng! Jed 2023-80 40-202 en
7. Cancone Tet al ESMO 2029. Abstaci LBAT. 8. Yue Dei a ELGG 2028, abstract 1080 PeerView
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Copyright © 2000-2024, PeerView
Understandi
Treatment Length and Median Follow-Up in Mo!
BIN Treatment length
Median follow-up
IMpower010"
KEYNOTE-091?
CheckMate -816°
AEGEAN*
Neotorch
KEYNOTE-67 1°
CheckMate -77T*
o 6 12 18 24 30 36 42
1. Felipe E et al. Lancet 2021/398-1344-1357. 2. O'Bien Met al Lancet One 2022/23-1274-1288, 3. Forde Petal N Engl Med, 2022:388-1973-1986,
à Heymach et a ARCR 2023, Abort CTO, § LS tl, ASCO 2023 Abstract 501.6, Maui Mei. N Engl Mod. 2029300491508 rn
7 Spier Jed al ESMO 2025. Abstract LBASO.. Cascone Tet al ESMO 2022 Abst LAT PeerView
PeerView.com/AWU827 Copyright © 2000-2024, PeerView
Treatment Length and Median Follow-Up in Mo!
BIN Treatment length
Median follow-up
IMpower010"
KEYNOTE-091?
CheckMate -816°
AEGEAN*
Neotorch
KEYNOTE-67 1°
CheckMate -77T*
o 6 12 18 24 30 36 42
1. Felipe E et al. Lancet 2021/398-1344-1357. 2. O'Bien Met al Lancet One 2022/23-1274-1288, 3. Forde Petal N Engl Med, 2022:388-1973-1986,
à Heymach et a ARCR 2023, Abort CTO, § LS tl, ASCO 2023 Abstract 501.6, Maui Mei. N Engl Mod. 2029300491508 rn
7 Spier Jed al ESMO 2025. Abstract LBASO.. Cascone Tet al ESMO 2022 Abst LAT PeerView
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Understanding Evidence: Pathologic Response Results!
60
3 vs 4 cycles
50 i
æ 40 pCR
e 30 248 Pathologic Complete Response
8 » 172 181 (No Viable Tumour at Resection)
10
o
CheckMate -816 AEGEAN Neotorch KEYNOTE-671 CheckMate -77T
60
gp = MPR
eo Major Pathologic Response
a 3 (10% Viable Tumour at Resection)
= >
10
o
CheckMate -816 AEGEAN Neotorch KEYNOTE-671 CheckMate -77T
1. Forde Pata. N Engl Mad. 202:9861979-1965. 2, Heyrach Jet al AACR 2023, Abstract CTOOS, 9. LUS et al ASCO 2023, Abstract 8501.
4 Watetee Metal Eng! Med, 2029-00 491-803 6. Spent Jet aL ESMO 2022, Abstract LAS. 6. Cascone Tetal ESMO 2023. Abstact LEA PeerView
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60
3 vs 4 cycles
50 i
æ 40 pCR
e 30 248 Pathologic Complete Response
8 » 172 181 (No Viable Tumour at Resection)
10
o
CheckMate -816 AEGEAN Neotorch KEYNOTE-671 CheckMate -77T
60
gp = MPR
eo Major Pathologic Response
a 3 (10% Viable Tumour at Resection)
= >
10
o
CheckMate -816 AEGEAN Neotorch KEYNOTE-671 CheckMate -77T
1. Forde Pata. N Engl Mad. 202:9861979-1965. 2, Heyrach Jet al AACR 2023, Abstract CTOOS, 9. LUS et al ASCO 2023, Abstract 8501.
4 Watetee Metal Eng! Med, 2029-00 491-803 6. Spent Jet aL ESMO 2022, Abstract LAS. 6. Cascone Tetal ESMO 2023. Abstact LEA PeerView
PeerView.com/AWU827 Copyright © 2000-2024, PeerView
Understanding Evidence: 2-Year EFS/DFS Results!”
506 Adjuvant Neoadjuvant Perioperative
$0] HR=081
y HR=0.76 HR=068 | HR=068 HR=0.40 HR=0.58 HR = 0.58
x 70
6 © 63.6 Sr, 65 633 ol 624
L 60 59
f=} 1524
ya 50
Ds 47 26.1
ti [40.6
= 40
8
2»
S 2
10
o
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A Fle E tal Lance 2021308134437 2 On Mall ane! Ost 222231274125 3 Fara Pata ELOO 202 Ase 64
"Jet al AACR 2023, Abstract CTOOS. 5. Lu S et al ASCO 2023 Abstract 8501. 6 Viakeite Het al. N Eng! Med. 2023389:491:503,
7 cone Toa. ESMO 202, Austral OA
PeerView
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506 Adjuvant Neoadjuvant Perioperative
$0] HR=081
y HR=0.76 HR=068 | HR=068 HR=0.40 HR=0.58 HR = 0.58
x 70
6 © 63.6 Sr, 65 633 ol 624
L 60 59
f=} 1524
ya 50
Ds 47 26.1
ti [40.6
= 40
8
2»
S 2
10
o
IMpower010 KEYNOTE-091 CheckMate -816 AEGEAN Neotorch KEYNOTE-671 CheckMate -77T
A Fle E tal Lance 2021308134437 2 On Mall ane! Ost 222231274125 3 Fara Pata ELOO 202 Ase 64
"Jet al AACR 2023, Abstract CTOOS. 5. Lu S et al ASCO 2023 Abstract 8501. 6 Viakeite Het al. N Eng! Med. 2023389:491:503,
7 cone Toa. ESMO 202, Austral OA
PeerView
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Understanding Evidence: 3-Year OS Results!
Adjuvant Neoadjuvant Perioperative
100 HR = 0.42 HR = 0.62 HR = 0.72
89.1 (95% CI: 0.23-0.78) (99.34% Cl: 0.36-1.05) (95% Cl: 0.56-0.93)
90 P= 012 P= 005
775 78
80 71
x 70 64 64
g 60
2 50
E
> 40
e 30
20
10
0
IMpower010? CheckMate -816 KEYNOTE-671
Stage IIA PO-L1 TC 50%, exclucing patent wih known EGFRUALK atea.
1.Felp E et al Ann Oncol, 2023:34507-919. 2 Forde Petal. ELOC 2023, Abstract 840, 3. Spice Jet al, ESMO 2023. Abstract LBASS.
PeerView.com/AWU827
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Adjuvant Neoadjuvant Perioperative
100 HR = 0.42 HR = 0.62 HR = 0.72
89.1 (95% CI: 0.23-0.78) (99.34% Cl: 0.36-1.05) (95% Cl: 0.56-0.93)
90 P= 012 P= 005
775 78
80 71
x 70 64 64
g 60
2 50
E
> 40
e 30
20
10
0
IMpower010? CheckMate -816 KEYNOTE-671
Stage IIA PO-L1 TC 50%, exclucing patent wih known EGFRUALK atea.
1.Felp E et al Ann Oncol, 2023:34507-919. 2 Forde Petal. ELOC 2023, Abstract 840, 3. Spice Jet al, ESMO 2023. Abstract LBASS.
PeerView.com/AWU827
PeerView
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Resolving Controversies
Neoadjuvant/Perioperative Chemo-IO by Stage?!
Stage
Forde 2022% Stage 65 62 aa 087 (048: +56)
Waous2023 Stage! se m LR 059 (040; 0.08}
Heymach 2023 ‘Stage Il 104 110 —- 0.76 [0.43; 1.34]
Cascone 2029 Stage! E a 081 1046: 143
Random effects model an = 071 (0.55:032)
Hatwpenety 0%, 7 = € 0.1, p= 0.88
significar son
: Foro 2022 Stage m 1 - 054 10.37,0301
it Vitae 20208 Sage ar zus - 057 (0.44:0741
Vikoloo 2023 Stgo 62 ss = 057 (0.26: 0.90}
Hoymach 20230 Stag il m 165 = 057 (0.39:0.83)
Heymacn 20230 Stage ill a 30 - 080 (0.52; 1.32]
Prvenc 2023 Stage ll Ed 2 —— 047 125;000
ites) Saga 202 2 039 (0.27:0.571
Cascone 2023 Stage il 16 19 en 051 1036:0721
Random ects model me 107 . 054 1048;052}
Hetwogmaiy: F 20% P20, p07
st
oz os 1 2 5
Faros Gena Fever Chen
1. Sonn etal. JAMA One 2024.10-521-653. PeerView
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Neoadjuvant/Perioperative Chemo-IO by Stage?!
Stage
Forde 2022% Stage 65 62 aa 087 (048: +56)
Waous2023 Stage! se m LR 059 (040; 0.08}
Heymach 2023 ‘Stage Il 104 110 —- 0.76 [0.43; 1.34]
Cascone 2029 Stage! E a 081 1046: 143
Random effects model an = 071 (0.55:032)
Hatwpenety 0%, 7 = € 0.1, p= 0.88
significar son
: Foro 2022 Stage m 1 - 054 10.37,0301
it Vitae 20208 Sage ar zus - 057 (0.44:0741
Vikoloo 2023 Stgo 62 ss = 057 (0.26: 0.90}
Hoymach 20230 Stag il m 165 = 057 (0.39:0.83)
Heymacn 20230 Stage ill a 30 - 080 (0.52; 1.32]
Prvenc 2023 Stage ll Ed 2 —— 047 125;000
ites) Saga 202 2 039 (0.27:0.571
Cascone 2023 Stage il 16 19 en 051 1036:0721
Random ects model me 107 . 054 1048;052}
Hetwogmaiy: F 20% P20, p07
st
oz os 1 2 5
Faros Gena Fever Chen
1. Sonn etal. JAMA One 2024.10-521-653. PeerView
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Resolving Controversies:
Neoadjuvant/Perioperative Chemo-IO for OS?!
All patients
Forde 2022 All patients
Wakelee 2023 All patients
Provencio 2023 All patients
Lu 2023 Alpatients
Random effects model
Heterogeneity: 1? = 0%, Y = <0.1, p = 067
1. Soon et al. JAMA Oncol 202410821853
PeerView.com/AWU827
179
397
57
179
400
29
202
810
0.2
ited
0.5
1
0.57 (0.38; 0.87]
0.72 (0.56; 0.93]
HTA
2 5
Favors Chemo-IO Favors Chemo
PeerView
Copyright © 2000-2024, PeerView
Neoadjuvant/Perioperative Chemo-IO for OS?!
All patients
Forde 2022 All patients
Wakelee 2023 All patients
Provencio 2023 All patients
Lu 2023 Alpatients
Random effects model
Heterogeneity: 1? = 0%, Y = <0.1, p = 067
1. Soon et al. JAMA Oncol 202410821853
PeerView.com/AWU827
179
397
57
179
400
29
202
810
0.2
ited
0.5
1
0.57 (0.38; 0.87]
0.72 (0.56; 0.93]
HTA
2 5
Favors Chemo-IO Favors Chemo
PeerView
Copyright © 2000-2024, PeerView
Resolving Controversies
Neoadjuvant/Perioperative Chemo-IO by PD-L1?!
1. Sonn et al. JAMA Oncol 2026:10:621-635
PeerView.com/AWU827
POL «1%
Forde 2022
Maroc 2023
Heymach 2029
20%
Cascone 2028
Random eects model
Hotoogenaty PU, 1 = 404, p=091
POL 140%
"aia 2029,
Hormach 2028
lw 20%
‘cascone 2023
Random ects model
Hera at 3% Pe <O1,p 2018
POL wor
Forde 2022.
waive 2023
eymach 202
Lu 2028
Cascone 2020
Random eects model
Hogar 32% > 04,9 =021
Pots <i
pour ais
Pots at,
POL ets,
Pou etm,
Pou 140%
PO: 140%
POL 149%
POL 140%
POL: 0%
POL: or
POL: sor
POL: o
POL: aso
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reerview
Copyright © 2000-2024, Peerview
Neoadjuvant/Perioperative Chemo-IO by PD-L1?!
1. Sonn et al. JAMA Oncol 2026:10:621-635
PeerView.com/AWU827
POL «1%
Forde 2022
Maroc 2023
Heymach 2029
20%
Cascone 2028
Random eects model
Hotoogenaty PU, 1 = 404, p=091
POL 140%
"aia 2029,
Hormach 2028
lw 20%
‘cascone 2023
Random ects model
Hera at 3% Pe <O1,p 2018
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Copyright © 2000-2024, Peerview
Incorporating Immunotherapy Into Treatment Plans in Resectable
NSCLC: What We Need to Know and Do
@ Select appropriate patients
@ Determine sequence of therapies
© Appropriate pre- and intraoperative nodal staging
© Understand the evidence
© Plan for potential technical challenges
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NSCLC: What We Need to Know and Do
@ Select appropriate patients
@ Determine sequence of therapies
© Appropriate pre- and intraoperative nodal staging
© Understand the evidence
© Plan for potential technical challenges
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Patient Selection Considerations
Staging
Physiologic Evaluation
Biomarker testing
CT
BEI PFTs
EBUS/med Cardiac eval
Brain MRI Exercise testing
Frailty assessment
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Staging
Physiologic Evaluation
Biomarker testing
CT
BEI PFTs
EBUS/med Cardiac eval
Brain MRI Exercise testing
Frailty assessment
PeerView
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IMMUNOTHERAPY IN RESECTABLE NSCLC | OUTLINE
PART 1
PART 2
Shining a Light on the Clinical Data
Supporting the Use of Adjuvant,
Neoadjuvant, and Perioperative
Immunotherapy in Resectable NSCLC
Closer to a Cure or Added Clinical
Complexity? Making Sense of the
Innovations for Immunotherapy in
Resectable NSCLC
‘© 2000-2024, PeerView
PART 1
PART 2
Shining a Light on the Clinical Data
Supporting the Use of Adjuvant,
Neoadjuvant, and Perioperative
Immunotherapy in Resectable NSCLC
Closer to a Cure or Added Clinical
Complexity? Making Sense of the
Innovations for Immunotherapy in
Resectable NSCLC
‘© 2000-2024, PeerView
allenging Clinical Questions
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Challenging Clinical Ques:
How do we decide between
neoadjuvant, adjuvant, and perioperative strategies?
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/AWUB27 Copyright © 2000-2024, Peerview
How do we decide between
neoadjuvant, adjuvant, and perioperative strategies?
PeerView
/AWUB27 Copyright © 2000-2024, Peerview
Challenging Clinical Que:
Is there a preferred platinum-based chemotherapy agent |
that should be used as part of perioperative therapy?
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Copyright © 2000-2024, PeerView
Is there a preferred platinum-based chemotherapy agent |
that should be used as part of perioperative therapy?
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Copyright © 2000-2024, PeerView
How can we balance improved clinical efficacy while |
avoiding overtreatment and increased toxicity?
|
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avoiding overtreatment and increased toxicity?
|
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Copyright © 2000-2024, Peerview
allenging Clinical Questions
PeerView
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allenging Clinical Questions
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Challenging Clinical Ques:
| Is there an optimum or minimum treatment duration in the
| adjuvant setting that we should utilise?
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| Is there an optimum or minimum treatment duration in the
| adjuvant setting that we should utilise?
PeerView
VAWU827 Copyright © 2000-2024, PeerView
Challenging Clinical Ques’
How does utilising perioperative immunotherapy approaches
impact long-term management of patients?
PeerView
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How does utilising perioperative immunotherapy approaches
impact long-term management of patients?
PeerView
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Conclusions & Key Takeaways
Copyright © 2000-2024,
Copyright © 2000-2024,
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