Illuminating the Path With Immunotherapy for Metastatic, Locally Advanced, and Early-Stage NSCLC: A Guide to Patient Assessment, Treatment Selection, and Multidisciplinary Collaboration Across the Disease Continuum
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Jun 27, 2024
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About This Presentation
Chair and Presenter, Sandip Patel, MD, Tina Cascone, MD, PhD, and Jonathan D. Spicer, MD, PhD, FRCSC, prepared useful Practice Aids pertaining to NSCLC for this CME/MOC/NCPD/AAPA/IPCE activity titled “Illuminating the Path With Immunotherapy for Metastatic, Locally Advanced, and Early-Stage NSCLC:...
Slide Content
NSCLC Treatment Algorithm
1
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
Stage and workup based on stage
• cT1abc, N0: PFT, bronch, mediastinal staging, PET
• cT2a-4, N0-3, M0-1: PFT, bronch, mediastinal staging, PET, brain MRI, and biomarker/mutation testing
Surgical candidate?
Lobectomy
(preferred)
or
segmentectomy/
wedge resection
(in select cases)
SBRT
or
conventionally
fractionated RT
Surgical resection
Test for PD-L1 status,
EGFR mutations,
and ALK rearrangements
Surgical resection
T1
N0
M0
Operable disease
Yes
Yes
No
No
Multidisciplinary discussion for
neoadjuvant candidacy
T1–2, N1–2, M0
T3–4, N0–1, M0
Neoadjuvant
chemoimmunotherapy
Neoadjuvant portion of
perioperative immunotherapy
Nivolumab + platinum-based
chemotherapy x 3 cycles
CheckMate -816: Nivo + chemo vs
chemo (see FDA approval)
mEFS: 31.6 vs 20.8 mo (HR, 0.63)
Pembrolizumab + platinum-containing chemotherapy x 4
cycles as neoadjuvant
KEYNOTE-671: Pembro + chemo vs placebo + chemo
(neoadjuvant) / pembro vs placebo (adjuvant)
(see FDA approval)
mOS: not reached vs 52.4 mo; mEFS: not reached vs 17 mo
Adjuvant chemotherapy
Platinum-based chemotherapy
LACE Meta-analysis: 5-y OS improvement of 5.4% vs no chemo
Atezolizumab x 16 cycles
Stage II-IIIA, PD-L1 ≥1% (see FDA approval)
Atezolizumab x 16 cycles
IMpower010: Atezo vs BSC
mDFS: NR vs 35.3 mo (HR, 0.66)
Pembrolizumab x 1 y
Stage IB (T2a ≥4 cm), II, or IIIA, regardless
of PD-L1 expression (see FDA approval)
Pembrolizumab x 1 y
PEARLS/KEYNOTE-091: Pembro vs placebo
mDFS: 53.6 vs 42.0 mo (HR, 0.76)
Adjuvant EGFR-targeted therapy
Osimertinib x 3 y
ADAURA: Osimertinib vs placebo
2-y DFS (stage II-IIIA): 90% vs 44% (HR, 0.17)
NSCLC treatment algorithm
Stage IB-IIIA
(resectable)Stage IA
Surgical resection
Adjuvant portion of perioperative immunotherapy
Pembrolizumab, up to 13 cycles
KEYNOTE-671: Pembro + chemo vs placebo + chemo
(neoadjuvant) / pembro vs placebo (adjuvant)
(see FDA approval)
mOS: not reached vs 52.4 mo; mEFS: not reached vs 17 mo
Yes
Adjuvant ALK-targeted therapy
Alectinib x 24 mo
ALINA: Alectinib vs chemo
mDFS: NR vs 41.3 mo
Adjuvant immunotherapy (stage II-IIIA)
ALK rearrangement
EGFR ex19del/
ex21 L858R
EGFR ex19del/
ex21 L858R
1
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
Stage and workup based on stage
• cT1abc, N0: PFT, bronch, mediastinal staging, PET
• cT2a-4, N0-3, M0-1: PFT, bronch, mediastinal staging, PET, brain MRI, and biomarker/mutation testing
Surgical candidate?
Lobectomy
(preferred)
or
segmentectomy/
wedge resection
(in select cases)
SBRT
or
conventionally
fractionated RT
Surgical resection
Test for PD-L1 status,
EGFR mutations,
and ALK rearrangements
Surgical resection
T1
N0
M0
Operable disease
Yes
Yes
No
No
Multidisciplinary discussion for
neoadjuvant candidacy
T1–2, N1–2, M0
T3–4, N0–1, M0
Neoadjuvant
chemoimmunotherapy
Neoadjuvant portion of
perioperative immunotherapy
Nivolumab + platinum-based
chemotherapy x 3 cycles
CheckMate -816: Nivo + chemo vs
chemo (see FDA approval)
mEFS: 31.6 vs 20.8 mo (HR, 0.63)
Pembrolizumab + platinum-containing chemotherapy x 4
cycles as neoadjuvant
KEYNOTE-671: Pembro + chemo vs placebo + chemo
(neoadjuvant) / pembro vs placebo (adjuvant)
(see FDA approval)
mOS: not reached vs 52.4 mo; mEFS: not reached vs 17 mo
Adjuvant chemotherapy
Platinum-based chemotherapy
LACE Meta-analysis: 5-y OS improvement of 5.4% vs no chemo
Atezolizumab x 16 cycles
Stage II-IIIA, PD-L1 ≥1% (see FDA approval)
Atezolizumab x 16 cycles
IMpower010: Atezo vs BSC
mDFS: NR vs 35.3 mo (HR, 0.66)
Pembrolizumab x 1 y
Stage IB (T2a ≥4 cm), II, or IIIA, regardless
of PD-L1 expression (see FDA approval)
Pembrolizumab x 1 y
PEARLS/KEYNOTE-091: Pembro vs placebo
mDFS: 53.6 vs 42.0 mo (HR, 0.76)
Adjuvant EGFR-targeted therapy
Osimertinib x 3 y
ADAURA: Osimertinib vs placebo
2-y DFS (stage II-IIIA): 90% vs 44% (HR, 0.17)
NSCLC treatment algorithm
Stage IB-IIIA
(resectable)Stage IA
Surgical resection
Adjuvant portion of perioperative immunotherapy
Pembrolizumab, up to 13 cycles
KEYNOTE-671: Pembro + chemo vs placebo + chemo
(neoadjuvant) / pembro vs placebo (adjuvant)
(see FDA approval)
mOS: not reached vs 52.4 mo; mEFS: not reached vs 17 mo
Yes
Adjuvant ALK-targeted therapy
Alectinib x 24 mo
ALINA: Alectinib vs chemo
mDFS: NR vs 41.3 mo
Adjuvant immunotherapy (stage II-IIIA)
ALK rearrangement
EGFR ex19del/
ex21 L858R
EGFR ex19del/
ex21 L858R
Stage IIIA (unresectable) or IIIB/C
Definitive chemoradiation → durvalumab
Concurrent platinum-based chemotherapy and radiation with
consolidation durvalumab
PACIFIC: Durvalumab vs placebo
mPFS: 16.8 vs 5.6 mo (HR, 0.52)
BRAF V600E
Dabrafenib + trametinib
a
BRF113928: Dabrafenib + trametinib single arm
ORR: 64% (95% CI, 46-79)
Encorafenib + binimetinib
a
PHAROS: Encorafenib + binimetinib single arm (see FDA approval)
Treatment-naïve patients, ORR: 75% (95% CI, 62-85); mDOR: NE (95% CI, 23.1-NE)
Previously treated patients, ORR: 46% (95% CI, 30-63); mDOR: 16.7 mo (95% CI, 7.4-NE)
Vemurafenib
AcSé: Vemurafenib single arm
ORR: 45%; mPFS: 5.2 mo; OS: 10 mo
2L: KRAS G12C
Sotorasib
CodeBreaK100: Sotorasib single arm
ORR: 37.1% (95% CI, 29-46); mPFS: 6.8 mo
Adagrasib
K RY STA L-1: Adagrasib single arm (see FDA approval)
ORR: 43% (95% CI, 34-53); mDOR: 8.5 mo
ALK
Alectinib
a
ALEX: Alectinib vs crizotinib
1-y PFS: 68.4% vs 48.7% (HR, 0.47)
Brigatinib
a
ALTA-1L: Brigatinib vs crizotinib
mPFS: 24 vs 11.1 mo (HR, 0.48)
Lorlatinib
a
CROWN: Lorlatinib vs crizotinib
mPFS: NR vs 9.3 mo (HR, 0.28); 1-y PFS: 78% vs 39%
Ceritinib
ASCEND-4: Ceritinib vs chemo
mPFS: 16.6 vs 8.1 mo (HR, 0.55)
Crizotinib
PROFILE 1007: Crizotinib vs chemo
mPFS: 7.7 vs 3 mo (HR, 0.49)
NTRK
Larotrectenib
a
NCT02122913/SCOUT/NAVIGATE : Larotrectenib single arm (see FDA approval)
ORR: 75% according to independent review and 80% according to investigator assessment
Entrectinib
a
ALKA/STARTRK: Entrectinib single arm (see FDA approval)
ORR: 70% (NSCLC)
RET
EGFR S768I, L861Q, and/or G719X
Selpercatinib
a
LIBRETTO-001: Selpercatinib single arm (see FDA approval)
ORR: 64%; mDOR: 17.5 mo
Pralsetinib
a
ARROW: Pralsetinib single arm (see FDA approval)
Treatment-naïve patients, ORR: 78% (95% CI, 68-85); mDOR: 13.4 mo (95% CI, 9.4-23.1)
Previously treated patients, ORR: 63% (95% CI, 54-71); mDOR: 38.8 mo (95% CI, 14.8-NE)
Cabozantinib
NCT01639508: Cabozantinib single arm
ORR: 28%
Osimertinib
a
FLAURA: Osimertinib vs erlotinib/gefitinib
mPFS: 18.9 vs 10.2 mo (HR, 0.46)
Erlotinib
EU RTAC: Erlotinib vs chemo
mPFS: 9.7 vs 5.2 mo (HR, 0.37)
Afatinib
a
LUX-Lung 3: Afatinib vs cis/pemetrexed
mPFS: 13.6 vs 6.9 mo (HR, 0.47)
Gefitinib
IFUM: Gefitinib single arm
mPFS: 9.7 mo
Dacomitinib
ARCHER 1050: Dacomitinib vs gefitinib
mOS: 34.1 vs 27 mo (HR, 0.75)
Amivantamab + carboplatin + pemetrexed (nonsquamous)
MARIPOSA-2: Amivantamb + chemo ± lazertinib vs chemo
mPFS: 6.3, 8.3 vs 4.2 mo (HR, 0.48, 0.44); ORR: 64%, 63% vs 36% (P < .001 for both)
EGFR (ex20)
Amivantamab
CHRYSALIS: Amivantamab single arm
CBR: 74% (95%CI, 63-83); mPFS: 8.3 mo
Amivantamb + carboplatin + pemetrexed (nonsquamous)
a
PAPILLON: Amivantamab + chemo vs chemo
mPFS: 11.4 vs 6.7 mo (HR, 0.4); ORR: 73% vs 47%
ROS1
Crizotinib
a
PROFILE 1001: Crizotinib single arm
ORR: 72% (95% CI, 58-84)
Entrectinib
a
ALK A & STARTRK: Entrectinib single arm
ORR: 67.1%; mPFS: 19 mo
Ceritinib
YONSEI: Ceritinib single arm
ORR: 67% (95% CI, 48-81)
Repotrectinib
a
TRIDENT-1: Repotrectinib single arm (see FDA approval)
ROS1 TKI-naïve patients, ORR: 79% (95% CI, 68-88); mDOR: 34.1 mo (95% CI, 25.6-NE)
Prior ROS1 inhibitor, ORR: 38% (95% CI, 25-52); mDOR: 14.8 mo (95% CI, 7.6-NE)
Lorlatinib
NCT01970865: Lorlatinib single arm
ROS TKI-naïve patients, ORR: 62%; Crizotinib pre-treated patients, ORR: 35%
EGFR (ex19 del or L858R)
Osimertinib
a
FLAURA: Osimertinib vs erlotinib/gefitinib
mPFS: 18.9 vs 10.2 mo (HR, 0.46)
Osimertinib + pemetrexed + cisplatin/carboplatin
FLAURA2: Osimertinib + chemo vs osimertinib (see FDA approval)
mPFS: 25.5 vs 16.7 mo (HR, 0.62)
Erlotinib
EU RTAC: Erlotinib vs chemo
mPFS: 9.7 vs 5.2 mo (HR, 0.37)
Afatinib
LUX-Lung 3: Afatinib vs cis/pemetrexed
mPFS: 13.6 vs 6.9 mo (HR, 0.47)
Gefitinib
IFUM: Gefitinib single arm
mPFS: 9.7 mo
Dacomitinib
ARCHER 1050: Dacomitinib vs gefitinib
mOS: 34.1 vs 27 mo (HR, 0.75)
Erlotinib + ramucirumab
R E L AY: Erlotinib + ramucirumab vs erlotinib
mPFS: 19.4 vs 12.4 mo (HR, 0.59)
Erlotinib + bevacizumab (nonsquamous)
ARTEMIS-CTONG1509 : Erlotinib + bevacizumab vs erlotinib
mPFS: 17.9 vs 11.2 mo (HR, 0.55)
Amivantamab + carboplatin + pemetrexed (nonsquamous)
MARIPOSA-2: Amivantamb + chemo ± lazertinib vs chemo
mPFS: 6.3, 8.3 vs 4.2 mo (HR, 0.48, 0.44); ORR: 64%, 63% vs 36% (P < .001 for both)
MET (exon 14)
Capmatinib
a
GEOMETRY mono-1: Capmatinib single arm (see FDA approval)
mPFS: 12.4 mo; treatment-naïve patients, ORR: 68% (95% CI, 55-80); DOR: 16.6 mo
Previously treated patients, ORR: 44% (95% CI, 34-54); DOR: 9.7 mo
Tepotinib
a
VISION: Tepotinib single arm
mPFS: 8.5-11 mo
Crizotinib
PROFILE 1001: Crizotinib single arm
ORR: 32%
2L: HER2
Trastuzumab deruxtecan
a
DESTINY-Lung02: T-DXd 5.4 mg/kg vs 6.4 mg/kg (see FDA approval)
ORR: 58% (98% CI, 43-71); mDOR: 8.7 mo (95% CI, 7.1-NE)
Trastuzumab emtansine
NCT02675829: Trastuzumab emtansine single arm
ORR: 44%
T1-2, N2–3, M0
T3, N1–3, M0
T4, N0–3, M0
Tx
Nx
M1
Actionable mutation detected
Mutation (broad NGS if possible) and PD-L1 testing
NSCLC treatment algorithm
Stage and workup based on stage
• cT1abc, N0: PFT, bronch, mediastinal staging, PET
• cT2a- 4, N0-3, M0-1: PFT, bronch, mediastinal staging, PET, brain MRI, and biomarker/mutation testing
Please see the next page for recommendations if no actionable mutation is detected
Stage IV
• EGFR
• ALK
• ROS1
• BRAF V600E
• RET
• MET (ex14)
• HER2
• NTRK1/2/3
• KRAS G12C
NSCLC Treatment Algorithm
1
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
Definitive chemoradiation → durvalumab
Concurrent platinum-based chemotherapy and radiation with
consolidation durvalumab
PACIFIC: Durvalumab vs placebo
mPFS: 16.8 vs 5.6 mo (HR, 0.52)
BRAF V600E
Dabrafenib + trametinib
a
BRF113928: Dabrafenib + trametinib single arm
ORR: 64% (95% CI, 46-79)
Encorafenib + binimetinib
a
PHAROS: Encorafenib + binimetinib single arm (see FDA approval)
Treatment-naïve patients, ORR: 75% (95% CI, 62-85); mDOR: NE (95% CI, 23.1-NE)
Previously treated patients, ORR: 46% (95% CI, 30-63); mDOR: 16.7 mo (95% CI, 7.4-NE)
Vemurafenib
AcSé: Vemurafenib single arm
ORR: 45%; mPFS: 5.2 mo; OS: 10 mo
2L: KRAS G12C
Sotorasib
CodeBreaK100: Sotorasib single arm
ORR: 37.1% (95% CI, 29-46); mPFS: 6.8 mo
Adagrasib
K RY STA L-1: Adagrasib single arm (see FDA approval)
ORR: 43% (95% CI, 34-53); mDOR: 8.5 mo
ALK
Alectinib
a
ALEX: Alectinib vs crizotinib
1-y PFS: 68.4% vs 48.7% (HR, 0.47)
Brigatinib
a
ALTA-1L: Brigatinib vs crizotinib
mPFS: 24 vs 11.1 mo (HR, 0.48)
Lorlatinib
a
CROWN: Lorlatinib vs crizotinib
mPFS: NR vs 9.3 mo (HR, 0.28); 1-y PFS: 78% vs 39%
Ceritinib
ASCEND-4: Ceritinib vs chemo
mPFS: 16.6 vs 8.1 mo (HR, 0.55)
Crizotinib
PROFILE 1007: Crizotinib vs chemo
mPFS: 7.7 vs 3 mo (HR, 0.49)
NTRK
Larotrectenib
a
NCT02122913/SCOUT/NAVIGATE : Larotrectenib single arm (see FDA approval)
ORR: 75% according to independent review and 80% according to investigator assessment
Entrectinib
a
ALKA/STARTRK: Entrectinib single arm (see FDA approval)
ORR: 70% (NSCLC)
RET
EGFR S768I, L861Q, and/or G719X
Selpercatinib
a
LIBRETTO-001: Selpercatinib single arm (see FDA approval)
ORR: 64%; mDOR: 17.5 mo
Pralsetinib
a
ARROW: Pralsetinib single arm (see FDA approval)
Treatment-naïve patients, ORR: 78% (95% CI, 68-85); mDOR: 13.4 mo (95% CI, 9.4-23.1)
Previously treated patients, ORR: 63% (95% CI, 54-71); mDOR: 38.8 mo (95% CI, 14.8-NE)
Cabozantinib
NCT01639508: Cabozantinib single arm
ORR: 28%
Osimertinib
a
FLAURA: Osimertinib vs erlotinib/gefitinib
mPFS: 18.9 vs 10.2 mo (HR, 0.46)
Erlotinib
EU RTAC: Erlotinib vs chemo
mPFS: 9.7 vs 5.2 mo (HR, 0.37)
Afatinib
a
LUX-Lung 3: Afatinib vs cis/pemetrexed
mPFS: 13.6 vs 6.9 mo (HR, 0.47)
Gefitinib
IFUM: Gefitinib single arm
mPFS: 9.7 mo
Dacomitinib
ARCHER 1050: Dacomitinib vs gefitinib
mOS: 34.1 vs 27 mo (HR, 0.75)
Amivantamab + carboplatin + pemetrexed (nonsquamous)
MARIPOSA-2: Amivantamb + chemo ± lazertinib vs chemo
mPFS: 6.3, 8.3 vs 4.2 mo (HR, 0.48, 0.44); ORR: 64%, 63% vs 36% (P < .001 for both)
EGFR (ex20)
Amivantamab
CHRYSALIS: Amivantamab single arm
CBR: 74% (95%CI, 63-83); mPFS: 8.3 mo
Amivantamb + carboplatin + pemetrexed (nonsquamous)
a
PAPILLON: Amivantamab + chemo vs chemo
mPFS: 11.4 vs 6.7 mo (HR, 0.4); ORR: 73% vs 47%
ROS1
Crizotinib
a
PROFILE 1001: Crizotinib single arm
ORR: 72% (95% CI, 58-84)
Entrectinib
a
ALK A & STARTRK: Entrectinib single arm
ORR: 67.1%; mPFS: 19 mo
Ceritinib
YONSEI: Ceritinib single arm
ORR: 67% (95% CI, 48-81)
Repotrectinib
a
TRIDENT-1: Repotrectinib single arm (see FDA approval)
ROS1 TKI-naïve patients, ORR: 79% (95% CI, 68-88); mDOR: 34.1 mo (95% CI, 25.6-NE)
Prior ROS1 inhibitor, ORR: 38% (95% CI, 25-52); mDOR: 14.8 mo (95% CI, 7.6-NE)
Lorlatinib
NCT01970865: Lorlatinib single arm
ROS TKI-naïve patients, ORR: 62%; Crizotinib pre-treated patients, ORR: 35%
EGFR (ex19 del or L858R)
Osimertinib
a
FLAURA: Osimertinib vs erlotinib/gefitinib
mPFS: 18.9 vs 10.2 mo (HR, 0.46)
Osimertinib + pemetrexed + cisplatin/carboplatin
FLAURA2: Osimertinib + chemo vs osimertinib (see FDA approval)
mPFS: 25.5 vs 16.7 mo (HR, 0.62)
Erlotinib
EU RTAC: Erlotinib vs chemo
mPFS: 9.7 vs 5.2 mo (HR, 0.37)
Afatinib
LUX-Lung 3: Afatinib vs cis/pemetrexed
mPFS: 13.6 vs 6.9 mo (HR, 0.47)
Gefitinib
IFUM: Gefitinib single arm
mPFS: 9.7 mo
Dacomitinib
ARCHER 1050: Dacomitinib vs gefitinib
mOS: 34.1 vs 27 mo (HR, 0.75)
Erlotinib + ramucirumab
R E L AY: Erlotinib + ramucirumab vs erlotinib
mPFS: 19.4 vs 12.4 mo (HR, 0.59)
Erlotinib + bevacizumab (nonsquamous)
ARTEMIS-CTONG1509 : Erlotinib + bevacizumab vs erlotinib
mPFS: 17.9 vs 11.2 mo (HR, 0.55)
Amivantamab + carboplatin + pemetrexed (nonsquamous)
MARIPOSA-2: Amivantamb + chemo ± lazertinib vs chemo
mPFS: 6.3, 8.3 vs 4.2 mo (HR, 0.48, 0.44); ORR: 64%, 63% vs 36% (P < .001 for both)
MET (exon 14)
Capmatinib
a
GEOMETRY mono-1: Capmatinib single arm (see FDA approval)
mPFS: 12.4 mo; treatment-naïve patients, ORR: 68% (95% CI, 55-80); DOR: 16.6 mo
Previously treated patients, ORR: 44% (95% CI, 34-54); DOR: 9.7 mo
Tepotinib
a
VISION: Tepotinib single arm
mPFS: 8.5-11 mo
Crizotinib
PROFILE 1001: Crizotinib single arm
ORR: 32%
2L: HER2
Trastuzumab deruxtecan
a
DESTINY-Lung02: T-DXd 5.4 mg/kg vs 6.4 mg/kg (see FDA approval)
ORR: 58% (98% CI, 43-71); mDOR: 8.7 mo (95% CI, 7.1-NE)
Trastuzumab emtansine
NCT02675829: Trastuzumab emtansine single arm
ORR: 44%
T1-2, N2–3, M0
T3, N1–3, M0
T4, N0–3, M0
Tx
Nx
M1
Actionable mutation detected
Mutation (broad NGS if possible) and PD-L1 testing
NSCLC treatment algorithm
Stage and workup based on stage
• cT1abc, N0: PFT, bronch, mediastinal staging, PET
• cT2a- 4, N0-3, M0-1: PFT, bronch, mediastinal staging, PET, brain MRI, and biomarker/mutation testing
Please see the next page for recommendations if no actionable mutation is detected
Stage IV
• EGFR
• ALK
• ROS1
• BRAF V600E
• RET
• MET (ex14)
• HER2
• NTRK1/2/3
• KRAS G12C
NSCLC Treatment Algorithm
1
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
a
Denotes NCCN-preferred regimens.
b
For patients who have no contraindications to PD-1 or PD-L1 inhibitors and who have a PS 0-1.
1. Adapted from an algorithm created by Aakash Desai, MBBS, MPH, and Matthew Ho, MD, PhD, with recent updates from NCCN Guidelines Version 5, 2024. Used with permission from the authors.
PD- L1 <1%
b
IMMUNOTHERAPY + CHEMOTHERAPY
SQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin + paclitaxel/nab-paclitaxel)
KEYNOTE-407: Pembro + chemo vs chemo
mPFS: 6.4 vs 4.8 mo (HR, 0.56); mOS: 15.9 vs 11.3 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(paclitaxel + carboplatin/cisplatin)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
NONSQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin/cisplatin + pemetrexed)
KEYNOTE-189: Pembro + chemo vs chemo
mPFS: 8.8 vs 4.9 mo (HR, 0.52); 12-mo OS: 69% vs 49% (HR, 0.49)
• Atezolizumab + chemotherapy (carboplatin + paclitaxel + bevacizumab)
IMpower150: Atezo + chemo vs chemo
mPFS: 8.3 vs 6.8 mo (HR, 0.62)
• Atezolizumab + chemotherapy (carboplatin + nab-paclitaxel)
IMpower130: Atezo + chemo vs chemo
mOS: 18.6 vs 13.9 mo (HR, 0.79); mPFS: 7.0 vs 5.5 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(carboplatin/cisplatin + pemetrexed)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
DUAL IMMUNOTHERAPY + CHEMOTHERAPY
SQUAMOUS:
• Nivolumab + ipilimumab + chemotherapy (paclitaxel/carboplatin)
CheckMate -9LA: Nivo/ipi + chemo vs chemo
mOS: 14.1 vs 10.7 mo
• Durvalumab + tremelimumab + chemotherapy (carboplatin + nab-paclitaxel)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
• Durvalumab + tremelimumab + chemotherapy (gemcitabine + carboplatin/cisplatin)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
NONSQUAMOUS:
• Nivolumab + ipilimumab + chemotherapy (paclitaxel/carboplatin)
CheckMate -9LA: Nivo/ipi + chemo vs chemo
mOS: 14.1 vs 10.7 mo
• Durvalumab + tremelimumab + chemotherapy (carboplatin + nab - paclitaxel)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
• Durvalumab + tremelimumab + chemotherapy (pemetrexed + carboplatin/cisplatin)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
DUAL IMMUNOTHERAPY
Nivolumab + ipilimumab
CheckMate -227: Nivo/ipi vs chemo
mOS: 17.1 vs 14.9 mo
DUAL IMMUNOTHERAPY
Nivolumab + ipilimumab
CheckMate -227: Nivo/ipi vs chemo
mOS: 17.1 vs 14.9 mo
DUAL IMMUNOTHERAPY + CHEMOTHERAPY
Nivolumab + ipilimumab + chemotherapy (pemetrexed + carboplatin/cisplatin)
CheckMate -9LA: Nivo/ipi + chemo vs chemo
mOS: 14.1 vs 10.7 mo
Durvalumab + tremelimumab + chemotherapy (carboplatin + nab-paclitaxel)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
Durvalumab + tremelimumab + chemotherapy (pemetrexed + carboplatin/cisplatin)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
IMMUNOTHERAPY MONOTHERAPY
Pembrolizumab
KEYNOTE-042: Pembro vs plat-based chemo
mOS: 16.7 vs 12.1 mo (HR, 0.81)
DUAL IMMUNOTHERAPY
Nivolumab + ipilimumab
CheckMate -227: Nivo/ipi vs chemo
mOS: 17.1 vs 14.9 mo
DUAL IMMUNOTHERAPY + CHEMOTHERAPY
Nivolumab + ipilimumab + chemotherapy (pemetrexed + carboplatin/cisplatin)
CheckMate -9LA: Nivo/ipi + chemo vs chemo
OS: 14.1 vs 10.7 mo
Durvalumab + tremelimumab + chemotherapy (carboplatin + nab-paclitaxel)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
Durvalumab + tremelimumab + chemotherapy (pemetrexed + carboplatin/
cisplatin)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
PD- L1 1%- 49%
IMMUNOTHERAPY + CHEMOTHERAPY
SQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin + paclitaxel/nab-paclitaxel)
KEYNOTE-407: Pembro + chemo vs chemo
mPFS: 6.4 vs 4.8 mo (HR, 0.56); mOS: 15.9 vs 11.3 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(paclitaxel + carboplatin/cisplatin)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
NONSQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin + pemetrexed)
KEYNOTE-189: Pembro + chemo vs chemo
mPFS: 8.8 vs 4.9 mo (HR, 0.52); 12-mo OS: 69% vs 49% (HR, 0.49)
• Atezolizumab + chemotherapy (carboplatin + paclitaxel + bevacizumab)
IMpower150: Atezo + chemo vs chemo
mPFS: 8.3 vs 6.8 mo (HR, 0.62)
• Atezolizumab + chemotherapy (carboplatin + albumin-bound paclitaxel)
IMpower130: Atezo + chemo vs chemo
mOS: 18.6 vs 13.9 mo (HR, 0.79); mPFS: 7.0 vs 5.5 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(carboplatin/cisplatin + pemetrexed)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
PD-L1 ≥50%
IMMUNOTHERAPY MONOTHERAPY
Pembrolizumab
a
KEYNOTE-024: Pembro vs platinum-based chemo
mPFS: 10.3 vs 6 mo (HR, 0.50)
Atezolizumab
a
I M p ower 110: Atezo vs platinum-based chemo
mOS: 20.1 vs 13.1 mo (HR, 0.59)
Cemiplimab
a
EMPOWER-Lung1: Cemi vs platinum-based chemo
mPFS: 8.2 vs 5.7 mo; mOS: NR vs 14.2 mo (HR, 0.57)
IMMUNOTHERAPY + CHEMOTHERAPY
SQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin + paclitaxel/nab-paclitaxel)
KEYNOTE-407: Pembro + chemo vs chemo
mPFS: 6.4 vs 4.8 mo (HR, 0.56); mOS: 15.9 vs 11.3 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(paclitaxel + carboplatin/cisplatin)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
NONSQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin/cisplatin + pemetrexed)
KEYNOTE-189: Pembro + chemo vs chemo
mPFS: 8.8 vs 4.9 mo (HR, 0.52); 12-mo OS: 69% vs 49% (HR, 0.49)
• Atezolizumab + chemotherapy (carboplatin + paclitaxel + bevacizumab)
IMpower150: Atezo + chemo vs chemo
mPFS: 8.3 vs 6.8 mo (HR, 0.62)
• Atezolizumab + chemotherapy (carboplatin + albumin-bound paclitaxel)
IMpower130: Atezo + chemo vs chemo
mOS: 18.6 vs 13.9 mo (HR, 0.79); mPFS: 7.0 vs 5.5 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(carboplatin/cisplatin + pemetrexed)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
• Cemiplimab + chemotherapy (paclitaxel + carboplatin or cisplatin)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
No actionable mutation detected (stratify based on PD-L1 staining %)
NSCLC Treatment Algorithm
1
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
Denotes NCCN-preferred regimens.
b
For patients who have no contraindications to PD-1 or PD-L1 inhibitors and who have a PS 0-1.
1. Adapted from an algorithm created by Aakash Desai, MBBS, MPH, and Matthew Ho, MD, PhD, with recent updates from NCCN Guidelines Version 5, 2024. Used with permission from the authors.
PD- L1 <1%
b
IMMUNOTHERAPY + CHEMOTHERAPY
SQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin + paclitaxel/nab-paclitaxel)
KEYNOTE-407: Pembro + chemo vs chemo
mPFS: 6.4 vs 4.8 mo (HR, 0.56); mOS: 15.9 vs 11.3 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(paclitaxel + carboplatin/cisplatin)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
NONSQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin/cisplatin + pemetrexed)
KEYNOTE-189: Pembro + chemo vs chemo
mPFS: 8.8 vs 4.9 mo (HR, 0.52); 12-mo OS: 69% vs 49% (HR, 0.49)
• Atezolizumab + chemotherapy (carboplatin + paclitaxel + bevacizumab)
IMpower150: Atezo + chemo vs chemo
mPFS: 8.3 vs 6.8 mo (HR, 0.62)
• Atezolizumab + chemotherapy (carboplatin + nab-paclitaxel)
IMpower130: Atezo + chemo vs chemo
mOS: 18.6 vs 13.9 mo (HR, 0.79); mPFS: 7.0 vs 5.5 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(carboplatin/cisplatin + pemetrexed)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
DUAL IMMUNOTHERAPY + CHEMOTHERAPY
SQUAMOUS:
• Nivolumab + ipilimumab + chemotherapy (paclitaxel/carboplatin)
CheckMate -9LA: Nivo/ipi + chemo vs chemo
mOS: 14.1 vs 10.7 mo
• Durvalumab + tremelimumab + chemotherapy (carboplatin + nab-paclitaxel)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
• Durvalumab + tremelimumab + chemotherapy (gemcitabine + carboplatin/cisplatin)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
NONSQUAMOUS:
• Nivolumab + ipilimumab + chemotherapy (paclitaxel/carboplatin)
CheckMate -9LA: Nivo/ipi + chemo vs chemo
mOS: 14.1 vs 10.7 mo
• Durvalumab + tremelimumab + chemotherapy (carboplatin + nab - paclitaxel)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
• Durvalumab + tremelimumab + chemotherapy (pemetrexed + carboplatin/cisplatin)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
DUAL IMMUNOTHERAPY
Nivolumab + ipilimumab
CheckMate -227: Nivo/ipi vs chemo
mOS: 17.1 vs 14.9 mo
DUAL IMMUNOTHERAPY
Nivolumab + ipilimumab
CheckMate -227: Nivo/ipi vs chemo
mOS: 17.1 vs 14.9 mo
DUAL IMMUNOTHERAPY + CHEMOTHERAPY
Nivolumab + ipilimumab + chemotherapy (pemetrexed + carboplatin/cisplatin)
CheckMate -9LA: Nivo/ipi + chemo vs chemo
mOS: 14.1 vs 10.7 mo
Durvalumab + tremelimumab + chemotherapy (carboplatin + nab-paclitaxel)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
Durvalumab + tremelimumab + chemotherapy (pemetrexed + carboplatin/cisplatin)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
IMMUNOTHERAPY MONOTHERAPY
Pembrolizumab
KEYNOTE-042: Pembro vs plat-based chemo
mOS: 16.7 vs 12.1 mo (HR, 0.81)
DUAL IMMUNOTHERAPY
Nivolumab + ipilimumab
CheckMate -227: Nivo/ipi vs chemo
mOS: 17.1 vs 14.9 mo
DUAL IMMUNOTHERAPY + CHEMOTHERAPY
Nivolumab + ipilimumab + chemotherapy (pemetrexed + carboplatin/cisplatin)
CheckMate -9LA: Nivo/ipi + chemo vs chemo
OS: 14.1 vs 10.7 mo
Durvalumab + tremelimumab + chemotherapy (carboplatin + nab-paclitaxel)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
Durvalumab + tremelimumab + chemotherapy (pemetrexed + carboplatin/
cisplatin)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
PD- L1 1%- 49%
IMMUNOTHERAPY + CHEMOTHERAPY
SQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin + paclitaxel/nab-paclitaxel)
KEYNOTE-407: Pembro + chemo vs chemo
mPFS: 6.4 vs 4.8 mo (HR, 0.56); mOS: 15.9 vs 11.3 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(paclitaxel + carboplatin/cisplatin)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
NONSQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin + pemetrexed)
KEYNOTE-189: Pembro + chemo vs chemo
mPFS: 8.8 vs 4.9 mo (HR, 0.52); 12-mo OS: 69% vs 49% (HR, 0.49)
• Atezolizumab + chemotherapy (carboplatin + paclitaxel + bevacizumab)
IMpower150: Atezo + chemo vs chemo
mPFS: 8.3 vs 6.8 mo (HR, 0.62)
• Atezolizumab + chemotherapy (carboplatin + albumin-bound paclitaxel)
IMpower130: Atezo + chemo vs chemo
mOS: 18.6 vs 13.9 mo (HR, 0.79); mPFS: 7.0 vs 5.5 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(carboplatin/cisplatin + pemetrexed)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
PD-L1 ≥50%
IMMUNOTHERAPY MONOTHERAPY
Pembrolizumab
a
KEYNOTE-024: Pembro vs platinum-based chemo
mPFS: 10.3 vs 6 mo (HR, 0.50)
Atezolizumab
a
I M p ower 110: Atezo vs platinum-based chemo
mOS: 20.1 vs 13.1 mo (HR, 0.59)
Cemiplimab
a
EMPOWER-Lung1: Cemi vs platinum-based chemo
mPFS: 8.2 vs 5.7 mo; mOS: NR vs 14.2 mo (HR, 0.57)
IMMUNOTHERAPY + CHEMOTHERAPY
SQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin + paclitaxel/nab-paclitaxel)
KEYNOTE-407: Pembro + chemo vs chemo
mPFS: 6.4 vs 4.8 mo (HR, 0.56); mOS: 15.9 vs 11.3 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(paclitaxel + carboplatin/cisplatin)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
NONSQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin/cisplatin + pemetrexed)
KEYNOTE-189: Pembro + chemo vs chemo
mPFS: 8.8 vs 4.9 mo (HR, 0.52); 12-mo OS: 69% vs 49% (HR, 0.49)
• Atezolizumab + chemotherapy (carboplatin + paclitaxel + bevacizumab)
IMpower150: Atezo + chemo vs chemo
mPFS: 8.3 vs 6.8 mo (HR, 0.62)
• Atezolizumab + chemotherapy (carboplatin + albumin-bound paclitaxel)
IMpower130: Atezo + chemo vs chemo
mOS: 18.6 vs 13.9 mo (HR, 0.79); mPFS: 7.0 vs 5.5 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(carboplatin/cisplatin + pemetrexed)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
• Cemiplimab + chemotherapy (paclitaxel + carboplatin or cisplatin)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
No actionable mutation detected (stratify based on PD-L1 staining %)
NSCLC Treatment Algorithm
1
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
Overview of Key Phase 3 Clinical Trials Investigating
Immunotherapies in Resectable NSCLC
1,2
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
1. https://clinicaltrials.gov. 2. https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications.
SURGERY
SURGERY
Neoadjuvant Immunotherapy (Approved)
Study Neoadjuvant Regimen Adjuvant Regimen
Adjuvant Immunotherapy (Approved)
AEGEAN Durvalumab + chemo x 4 cycles Durvalumab ~1 year
CheckMate -77T Nivolumab + chemo x 4 cycles Nivolumab ~1 year
KEYNOTE-671 Pembrolizumab + chemo x 4 cycles Pembrolizumab ~1 year
CheckMate -816
IMpower010
KEYNOTE-091
Nivolumab + chemo x 3 cycles
Chemo atezolizumab ~1 y (PD-L1 ≥1%)
Chemo (optional) pembrolizumab ~1 year
FDA
approved
FDA
approved
FDA
approved
SURGERY
Immunotherapies in Resectable NSCLC
1,2
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
1. https://clinicaltrials.gov. 2. https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications.
SURGERY
SURGERY
Neoadjuvant Immunotherapy (Approved)
Study Neoadjuvant Regimen Adjuvant Regimen
Adjuvant Immunotherapy (Approved)
AEGEAN Durvalumab + chemo x 4 cycles Durvalumab ~1 year
CheckMate -77T Nivolumab + chemo x 4 cycles Nivolumab ~1 year
KEYNOTE-671 Pembrolizumab + chemo x 4 cycles Pembrolizumab ~1 year
CheckMate -816
IMpower010
KEYNOTE-091
Nivolumab + chemo x 3 cycles
Chemo atezolizumab ~1 y (PD-L1 ≥1%)
Chemo (optional) pembrolizumab ~1 year
FDA
approved
FDA
approved
FDA
approved
SURGERY
Immune-Related Adverse Events of Cancer Immunotherapies
1-6
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
Immune checkpoint inhibitors (ICIs)—which are monoclonal antibodies against
CTLA-4, PD-1, or PD-L1—have transformed treatment of many cancer types.
However, these treatments are associated with immune-related adverse events (irAEs).
Pre-existing autoimmune disease
is a strong risk factor for irAEs
Mechanism of irAEs
• CTLA-4 inhibitors: an imbalance in the ratio of regulatory T cells to type 17 T helper cells,
autoantibody production, and complement-mediated cellular damage
• PD-1/PD-L1 inhibitors: less well understood but could be due to reduced regulatory T cell numbers
Diagnostic
workup of
individuals
with suspected
irAEs depends
on the affected
organ
SYSTEMIC
Sicca syndr ome and v asculitis
irAEs can r ange
in severity and
affect almost
any or gan
Polyneur opathy
Uveitis
Interstitial
lung
disease
Hepatitis
Vitiligo
Myalgia
and
myositis
Enterocolitis
Thyroiditis
Hypophysiti s
Myocar ditis
Adrenitis
Arthralgia
and
arthritis
Monitoring organ function during ICI
therapy to enable early detection of
irAEs is warranted only for some
organs, such as thyroid and liver
Endocrinopathies: most common
toxicities associated with
PD-(L)1 monotherapy
Most common fatal
toxicity associated
with PD-(L)1/CTLA-4
combination therapy
Pneumonitis: most
common fatal toxicity
associated with PD-(L)1
monotherapy
Common toxicity
associated with
immunotherapy and targeted
therapy combinations
Cutaneous toxicities
are the earliest toxicity
associated with PD-(L)1
monotherapy and
combinations
Nephritis
Common toxicity
associated
with chemo +
IO regimens
Patterns and Duration of Various irAEs
While onset of irAEs is generally 2 to 16 weeks after ICI initiation, some reports
have noted onset within a few days of starting therapy and >1 year after completion.
An irAE that occurs >3 months after ICI discontinuation is a delayed/late-onset irAE.
Some irAEs are recurrent (ie, occurring in the same organ or >1 time after
discontinuation), while others are chronic and can be active (ie, requiring
immunosuppression) or inactive (ie, not requiring immunosuppression).
468101214 >30
Duration of Treatment, wk
PD-1/PD-L1 Inhibitors
Toxicity Grade
468101214 >30
Duration of Treatment, wk
PD-1/PD-L1 + CTLA-4 Inhibitors
Toxicity Grade
468101214 >30
CTLA-4 Inhibitors
Duration of Treatment, wk
Toxicity Grade
Colitis
Liver toxicity
Skin toxicity,
rash, or pruritus
Pneumonitis
Endocrinopathy
Nephritis
Become Aware and Stay Vigilant
1-6
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
Immune checkpoint inhibitors (ICIs)—which are monoclonal antibodies against
CTLA-4, PD-1, or PD-L1—have transformed treatment of many cancer types.
However, these treatments are associated with immune-related adverse events (irAEs).
Pre-existing autoimmune disease
is a strong risk factor for irAEs
Mechanism of irAEs
• CTLA-4 inhibitors: an imbalance in the ratio of regulatory T cells to type 17 T helper cells,
autoantibody production, and complement-mediated cellular damage
• PD-1/PD-L1 inhibitors: less well understood but could be due to reduced regulatory T cell numbers
Diagnostic
workup of
individuals
with suspected
irAEs depends
on the affected
organ
SYSTEMIC
Sicca syndr ome and v asculitis
irAEs can r ange
in severity and
affect almost
any or gan
Polyneur opathy
Uveitis
Interstitial
lung
disease
Hepatitis
Vitiligo
Myalgia
and
myositis
Enterocolitis
Thyroiditis
Hypophysiti s
Myocar ditis
Adrenitis
Arthralgia
and
arthritis
Monitoring organ function during ICI
therapy to enable early detection of
irAEs is warranted only for some
organs, such as thyroid and liver
Endocrinopathies: most common
toxicities associated with
PD-(L)1 monotherapy
Most common fatal
toxicity associated
with PD-(L)1/CTLA-4
combination therapy
Pneumonitis: most
common fatal toxicity
associated with PD-(L)1
monotherapy
Common toxicity
associated with
immunotherapy and targeted
therapy combinations
Cutaneous toxicities
are the earliest toxicity
associated with PD-(L)1
monotherapy and
combinations
Nephritis
Common toxicity
associated
with chemo +
IO regimens
Patterns and Duration of Various irAEs
While onset of irAEs is generally 2 to 16 weeks after ICI initiation, some reports
have noted onset within a few days of starting therapy and >1 year after completion.
An irAE that occurs >3 months after ICI discontinuation is a delayed/late-onset irAE.
Some irAEs are recurrent (ie, occurring in the same organ or >1 time after
discontinuation), while others are chronic and can be active (ie, requiring
immunosuppression) or inactive (ie, not requiring immunosuppression).
468101214 >30
Duration of Treatment, wk
PD-1/PD-L1 Inhibitors
Toxicity Grade
468101214 >30
Duration of Treatment, wk
PD-1/PD-L1 + CTLA-4 Inhibitors
Toxicity Grade
468101214 >30
CTLA-4 Inhibitors
Duration of Treatment, wk
Toxicity Grade
Colitis
Liver toxicity
Skin toxicity,
rash, or pruritus
Pneumonitis
Endocrinopathy
Nephritis
Become Aware and Stay Vigilant
Immune-Related Adverse Events of Cancer Immunotherapies
1-6
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
General Management Recommendations
Increasing intensity
of treatment required
Grade 2Grade 1 Grade 3 Grade 4
ModerateMild Severe Very severe
Symptomatic and suppor tive therapy
Stop treatment
Some irAEs are unresponsive or resistant to treatment with steroids, while others
are steroid-dependent, requiring chronic treatment (≥12 weeks)
Oral steroids Intravenous steroids. ------------ >
•Referral to specialist
•Strong immune suppressive treatment
Increasing grade of irAE
Intravenous steroids
Steroids (PO/IV): 1-2 mg/kg/d
prednisone or equivalent,
slowly taper over 4-6 weeks
For some AEs, treatment can be
restarted after resolution (eg, rash);
generally, ICI can be continued
with endocrinopathies
once managed
Managed in outpatient/
communi ty setting
Generally requires
hospital admission
1-6
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
General Management Recommendations
Increasing intensity
of treatment required
Grade 2Grade 1 Grade 3 Grade 4
ModerateMild Severe Very severe
Symptomatic and suppor tive therapy
Stop treatment
Some irAEs are unresponsive or resistant to treatment with steroids, while others
are steroid-dependent, requiring chronic treatment (≥12 weeks)
Oral steroids Intravenous steroids. ------------ >
•Referral to specialist
•Strong immune suppressive treatment
Increasing grade of irAE
Intravenous steroids
Steroids (PO/IV): 1-2 mg/kg/d
prednisone or equivalent,
slowly taper over 4-6 weeks
For some AEs, treatment can be
restarted after resolution (eg, rash);
generally, ICI can be continued
with endocrinopathies
once managed
Managed in outpatient/
communi ty setting
Generally requires
hospital admission
Immune-Related Adverse Events of Cancer Immunotherapies
1-6
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
Diagnosis and Management of Pulmonary irAEs
Hold immunotherapy and reassess in 1-2 weeks
Pulse oximetry rest and ambulation
Consider chest imaging with CT (with contrast preferred)
Repeat in 3-4 weeks
Moderate (grade 2): 25%-50%
lung involved
Severe (grade 3-4)
Grade 3: all lobes of lung or
>50% of lung parenchyma;
limited ADLs, oxygen requirement
Grade 4: life-threatening
Hold immunotherapy
Infectious workup (nasal swab, sputum, blood)
Consider bronchoscopy and BAL
Chest imaging with CT contrast
Repeat in 3-4 weeks
Consider empiric antibiotics
Refractory: methylprednisolone 1-2 mg/m
2
/day; if no response in 3-4 days, treat as grade 3
Permanently discontinue immunotherapy and move to inpatient care
Infectious workup (nasal swab, sputum, blood)
Pulmonary and infectious disease consultation
Bronchoscopy with BAL
Empiric antibiotics
Methylprednisolone 1-2 mg/m
2
/day; when grade 1, taper over 6 weeks
Refractory: infliximab, mycophenolate, or IVIG
Pneumonitis: focal or diffuse inflammation of the lung parenchyma (typically identified on CT imaging)
Diagnostic workup: CXR, CT, pulse oximetry; for grade ≥2, may include infectious workup
Mild (grade 1): <25% lung
involved
Additional considerations
• GI and pneumocystis prophylaxis may be offered to patients on prolonged steroid use (>12 weeks)
• Consider calcium and vitamin D supplementation with prolonged steroid use
• Bronchoscopy and biopsy; if clinical picture is consistent with pneumonitis, no need for biopsy
Supportive care: smoking cessation and vaccinations (influenza, pneumococcal)
1-6
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
Diagnosis and Management of Pulmonary irAEs
Hold immunotherapy and reassess in 1-2 weeks
Pulse oximetry rest and ambulation
Consider chest imaging with CT (with contrast preferred)
Repeat in 3-4 weeks
Moderate (grade 2): 25%-50%
lung involved
Severe (grade 3-4)
Grade 3: all lobes of lung or
>50% of lung parenchyma;
limited ADLs, oxygen requirement
Grade 4: life-threatening
Hold immunotherapy
Infectious workup (nasal swab, sputum, blood)
Consider bronchoscopy and BAL
Chest imaging with CT contrast
Repeat in 3-4 weeks
Consider empiric antibiotics
Refractory: methylprednisolone 1-2 mg/m
2
/day; if no response in 3-4 days, treat as grade 3
Permanently discontinue immunotherapy and move to inpatient care
Infectious workup (nasal swab, sputum, blood)
Pulmonary and infectious disease consultation
Bronchoscopy with BAL
Empiric antibiotics
Methylprednisolone 1-2 mg/m
2
/day; when grade 1, taper over 6 weeks
Refractory: infliximab, mycophenolate, or IVIG
Pneumonitis: focal or diffuse inflammation of the lung parenchyma (typically identified on CT imaging)
Diagnostic workup: CXR, CT, pulse oximetry; for grade ≥2, may include infectious workup
Mild (grade 1): <25% lung
involved
Additional considerations
• GI and pneumocystis prophylaxis may be offered to patients on prolonged steroid use (>12 weeks)
• Consider calcium and vitamin D supplementation with prolonged steroid use
• Bronchoscopy and biopsy; if clinical picture is consistent with pneumonitis, no need for biopsy
Supportive care: smoking cessation and vaccinations (influenza, pneumococcal)
Immune-Related Adverse Events of Cancer Immunotherapies
1-6
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
Guideline Management Recommendations
1. Ramos-Casals M et al. Nat Rev Dis Primers. 2020;6:38. 2. Martins F et al. Nat Rev Clin Oncol. 2019;16:563-580. 3. O’Leary CL et al. J Thorac Oncol. 2023;19:395-408. 4. Naidoo J et al. J Immunother Cancer. 2023;11:e006398. 5. Provided courtesy of Prof. Peter Schmidt, FRCP, MD, PhD.
6. Brahmer JR et al. J Clin Oncol. 2018;36:1714 -178 6 .
1-6
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
Guideline Management Recommendations
1. Ramos-Casals M et al. Nat Rev Dis Primers. 2020;6:38. 2. Martins F et al. Nat Rev Clin Oncol. 2019;16:563-580. 3. O’Leary CL et al. J Thorac Oncol. 2023;19:395-408. 4. Naidoo J et al. J Immunother Cancer. 2023;11:e006398. 5. Provided courtesy of Prof. Peter Schmidt, FRCP, MD, PhD.
6. Brahmer JR et al. J Clin Oncol. 2018;36:1714 -178 6 .
lungevity.org
• Patients and providers joined forces to make a discussion tool that helps
patients understand how their biomarker test results influence choosing the right
treatment for their solid-tumor cancer
• This discussion guide can support people with solid-tumor cancer to ask
their doctor or nurse the right questions about biomarker testing, ensure they
received the optimal level of biomarker testing, and understand how biomarker
testing can expand their optimal treatment options, including clinical trials
• The guide can also be used by healthcare providers to teach their patients
about how biomarker test results are used to make decisions about optimal
treatment and clinical trial options
LUNGevity offers a simplified guide to biomarker testing discussions for
patients and their healthcare team. It is available for download and can
be personalized with your institution’s logo and contact details.
The next page includes a tool designed for people with solid-tumor
cancer to use in communication about biomarker results
with their healthcare providers
LUNGevity Foundation
Biomarker Testing Discussion Guide for Patients
Full abbreviations, accreditation, and disclosure information available at
PeerView.com/ZUT40
• Patients and providers joined forces to make a discussion tool that helps
patients understand how their biomarker test results influence choosing the right
treatment for their solid-tumor cancer
• This discussion guide can support people with solid-tumor cancer to ask
their doctor or nurse the right questions about biomarker testing, ensure they
received the optimal level of biomarker testing, and understand how biomarker
testing can expand their optimal treatment options, including clinical trials
• The guide can also be used by healthcare providers to teach their patients
about how biomarker test results are used to make decisions about optimal
treatment and clinical trial options
LUNGevity offers a simplified guide to biomarker testing discussions for
patients and their healthcare team. It is available for download and can
be personalized with your institution’s logo and contact details.
The next page includes a tool designed for people with solid-tumor
cancer to use in communication about biomarker results
with their healthcare providers
LUNGevity Foundation
Biomarker Testing Discussion Guide for Patients
Full abbreviations, accreditation, and disclosure information available at
PeerView.com/ZUT40
Understanding Your Lung Cancer
Can Lead to Better Treatment Options
1. Has the cancer been tested for all biomarkers?
2. When is a tissue biomarker test necessary?
3. When is a blood biomarker test (ie, liquid biopsy) necessary?
4. How can I get a copy of my biomarker testing report?
5. Who will explain my biomarker testing results to me?
6. Is cancer biomarker testing the same as genetic testing for inherited cancer?
Are my family/children at risk?
7. Will I ever have to have more biomarker testing?
This tool is designed for people with solid-tumor cancer to use in communication
about biomarker results with their healthcare providers.
Was my tumor tested for biomarkers?
a
Did my test results show any biomarkers?
Let’s discuss your options
Based on my biomarker
results, how do we
decide what is the best
treatment for me?
Based on my
results, how
do we
decide if a
treatment
or clinical
trial is right
for me?
Would
more tests
offer more
treatment
options?
Let’s
discuss
the
approved
and
available
treatment
options
Let’s
discuss
other
potential
treatments
(ie, clinical
trials)
Can you get more tissue?
Let’s discuss
your options
What
resources
are
available
to help
pay for
the
costs?
NO
NO
Tissue
Will I need
another
biopsy?
We could test
tissue and/or
your blood
Blood
How long until I get
the results from the
repeat testing?
Could I get a
blood test
(liquid biopsy)?
Has my cancer been tested
for all treatable biomarkers
and biomarkers for
clinical trial
NO Why?
NO NO
No, because there was not
enough tissue for testing
No
biomarkers
NO
Will my insurance
cover the testing?
Trusting your core team
and treatment plan is
important. Seeking a
second opinion may
increase your trust in
your care plan.
lungevity.org
Suggested
questions
to ask
your team:
YES
YES
YESYES
YES
Yes, there are biomarkers
we can use to make a
treatment plan
Yes, but none that we can
use to make a treatment
plan at this time
a
Biomarkers are changes in the cancer cells that may help guide treatment. Most biomarkers used to guide treatment plans are not passed on to children/family.
Developed by LUNGevity Foundation in partnership with clinical experts and patients with cancer.
Can Lead to Better Treatment Options
1. Has the cancer been tested for all biomarkers?
2. When is a tissue biomarker test necessary?
3. When is a blood biomarker test (ie, liquid biopsy) necessary?
4. How can I get a copy of my biomarker testing report?
5. Who will explain my biomarker testing results to me?
6. Is cancer biomarker testing the same as genetic testing for inherited cancer?
Are my family/children at risk?
7. Will I ever have to have more biomarker testing?
This tool is designed for people with solid-tumor cancer to use in communication
about biomarker results with their healthcare providers.
Was my tumor tested for biomarkers?
a
Did my test results show any biomarkers?
Let’s discuss your options
Based on my biomarker
results, how do we
decide what is the best
treatment for me?
Based on my
results, how
do we
decide if a
treatment
or clinical
trial is right
for me?
Would
more tests
offer more
treatment
options?
Let’s
discuss
the
approved
and
available
treatment
options
Let’s
discuss
other
potential
treatments
(ie, clinical
trials)
Can you get more tissue?
Let’s discuss
your options
What
resources
are
available
to help
pay for
the
costs?
NO
NO
Tissue
Will I need
another
biopsy?
We could test
tissue and/or
your blood
Blood
How long until I get
the results from the
repeat testing?
Could I get a
blood test
(liquid biopsy)?
Has my cancer been tested
for all treatable biomarkers
and biomarkers for
clinical trial
NO Why?
NO NO
No, because there was not
enough tissue for testing
No
biomarkers
NO
Will my insurance
cover the testing?
Trusting your core team
and treatment plan is
important. Seeking a
second opinion may
increase your trust in
your care plan.
lungevity.org
Suggested
questions
to ask
your team:
YES
YES
YESYES
YES
Yes, there are biomarkers
we can use to make a
treatment plan
Yes, but none that we can
use to make a treatment
plan at this time
a
Biomarkers are changes in the cancer cells that may help guide treatment. Most biomarkers used to guide treatment plans are not passed on to children/family.
Developed by LUNGevity Foundation in partnership with clinical experts and patients with cancer.
LUNGevity Foundation
Lung Cancer Patient Resource Compendium
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
LUNGevity is transforming how people are diagnosed and live
with lung cancer through research, education, and support
LUNGevity educational materials order form for providers:
www.lungevity.org/order-materials
The next page includes useful links to resources for patients with lung cancer
lungevity.org
Lung Cancer Patient Resource Compendium
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
LUNGevity is transforming how people are diagnosed and live
with lung cancer through research, education, and support
LUNGevity educational materials order form for providers:
www.lungevity.org/order-materials
The next page includes useful links to resources for patients with lung cancer
lungevity.org
LUNGevity Foundation
Lung Cancer Patient Resource Compendium
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
• The Lung Cancer 101 Website
provides a guide to understanding the
basics of lung cancer
• The Lung Cancer Support
Community message boards offer
24/7 peer-to-peer support and
information
• The LifeLine Program matches
patients and care partners to mentors
LUNGevity offers the largest online network of peer-to-peer and one-on-one support,
plus in-person survivorship programs for all people affected by lung cancer
LUNGevity hosts weekly lung cancer support Virtual Meetups
for patients, survivors, caregivers, and friends and family members of people
with lung cancer to virtually connect face-to-face with others across the country
Please call 312- 407- 6116 for more information
• The Lung Cancer HELPLine
offers toll-free, personalized
support in English and Spanish
• Patient Gateways help navigate
specific types of lung cancer
• LUNGevity’s Hope Summit is
designed to inform, connect, and
empower anyone who has been
affected by lung cancer
lungevity.org
Lung Cancer Patient Resource Compendium
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUT40
• The Lung Cancer 101 Website
provides a guide to understanding the
basics of lung cancer
• The Lung Cancer Support
Community message boards offer
24/7 peer-to-peer support and
information
• The LifeLine Program matches
patients and care partners to mentors
LUNGevity offers the largest online network of peer-to-peer and one-on-one support,
plus in-person survivorship programs for all people affected by lung cancer
LUNGevity hosts weekly lung cancer support Virtual Meetups
for patients, survivors, caregivers, and friends and family members of people
with lung cancer to virtually connect face-to-face with others across the country
Please call 312- 407- 6116 for more information
• The Lung Cancer HELPLine
offers toll-free, personalized
support in English and Spanish
• Patient Gateways help navigate
specific types of lung cancer
• LUNGevity’s Hope Summit is
designed to inform, connect, and
empower anyone who has been
affected by lung cancer
lungevity.org
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