Co-Chairs and Presenter Jessica Donington, MD, Jonathan D. Spicer, MD, PhD, FRCSC, and Patrick M. Forde, MD, prepared useful Practice Aids pertaining to NSCLC for this CME/MOC/CC/AAPA activity titled “A Practical Guide for Making Multidisciplinary Decisions About Neoadjuvant and/or Adjuvant Immunotherapy in Resectable NSCLC.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/CC/AAPA information, and to apply for credit, please visit us at https://bit.ly/3MQVu5l. CME/MOC/CC/AAPA credit will be available until February 27, 2025.

1. Treatment Algorithm for Resectable NSCLC1
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QRX40
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
Mutational testing (if not conducted earlier)
EGFR ex19del/ex21 L858R present?
Surgical resection
T1
N0
M0
Operable disease
Yes
Yes
Yes
No
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
Adjuvant immunotherapy (stage II-IIIA)
Atezolizumab x 16 cycles
StageII-IIIA,PD-L1≥1%(seeFDAapproval)
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 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
1. Adapted from an algorithm created by Aakash Desai, MBBS, MPH, and Matthew Ho, MD, PhD. Used with permission from the authors.

2. Immune-Related Adverse Events of Cancer Immunotherapies
Become Aware and Stay Vigilant
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QRX40
What Are irAEs?1
• Immune checkpoint inhibitors are associated with important clinical benefits, but general immunologic enhancement
can also lead to a unique spectrum of immune-related adverse events
• Any organ system can be affected, but more commonly occurring are pulmonary (pneumonitis), dermatologic (rash, pruritus,
blisters, ulcers, vitiligo), gastrointestinal (diarrhea, enterocolitis, transaminitis, hepatitis, pancreatitis), and endocrine
(thyroiditis, hypophysitis, adrenal insufficiency) irAEs
Endocrine
Hyper- or hypothyroidism
Hypophysitis
Adrenal insufficiency
Diabetes
Hepatic
Hepatitis
Renal
Nephritis
Dermatologic
Rash
Pruritus
Psoriasis
Vitiligo
DRESS
Stevens-Johnson
Hematologic
Hemolytic anemia
Thrombocytopenia
Neutropenia
Hemophilia
Ocular
Uveitis
Conjunctivitis
Scleritis, episcleritis
Blepharitis
Retinitis
Respiratory
Pneumonitis
Pleuritis
Sarcoid-like granulomatosis
Cardiovascular
Myocarditis
Pericarditis
Vasculitis
Gastrointestinal
Colitis
Ileitis
Pancreatitis
Gastritis
Neurologic
Neuropathy
Guillain Barŕe
Myelopathy
Encephalitis
Myasthenia
Musculoskeletal
Arthritis
Dermatomyositis
01 Prevention
02 Anticipation
03 Detection
04 Treatment
05 Monitoring
01
02
03
04
05

3. Immune-Related Adverse Events of Cancer Immunotherapies
Become Aware and Stay Vigilant
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QRX40
General Recommendations for Treating irAEs2-5
Increasing
intensity
of
treatment
required
Grade 2
Grade 1 Grade 3 Grade 4
Moderate
Mild Severe Very severe
Symptomatic supportive therapy
Stop treatment
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/
community setting
Generally requires
hospital admission

4. Immune-Related Adverse Events of Cancer Immunotherapies
Become Aware and Stay Vigilant
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QRX40
 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/m2
/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/m2
/day; when grade 1, taper over 6 weeks
 Refractory: infliximab, mycophenolate, or IVIG
How Should Pulmonary irAEs Be Diagnosed and Managed?2,6
 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)

5. Immune-Related Adverse Events of Cancer Immunotherapies
Become Aware and Stay Vigilant
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QRX40
1. Champiat S et al. Ann Oncol. 2016;27:559-574. 2. Brahmer JR et al. J Clin Oncol. 2018;36:1714-1786. 3. https://www.esmo.org/content/download/124130/2352601/1/ESMO-Patient-Guide-on-Immunotherapy-Side-Effects.pdf. 4. NCCN Clinical Practice Guidelines in Oncology.
Management of Immunotherapy-Related Toxicities. Version 3.2023. https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf. 5. Puzanov I et al. J Immunother Cancer. 2017;5:95. 6. Provided courtesy of Marianne Davies, DNP, ACNP, AOCNP, FAAN, 2021; adapted
from AIM with Immunotherapy, NCCN, and CTCAE. 7. https://ascopubs.org/doi/full/10.1200/JCO.21.01440. 8. https://www.sitcancer.org/research/cancer-immunotherapy-guidelines/irae/immune-checkpoint-inhibitor-related-adverse-events.
Additional Guideline Recommendations for Treating irAEs3,4,7,8

6. Overview of Key Phase 3 Clinical Trials Investigating
Immunotherapies in Resectable NSCLC1,2
Full abbreviations, accreditation, and disclosure information available at PeerView.com/QRX40
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