Harnessing the Power of the Latest Clinical and Research Advances in SCLC: How to Accelerate Progress and Improve Patient Outcomes With Current and Emerging Therapies
Chair and Presenter Taofeek K. Owonikoko, MD, PhD, Hossein Borghaei, DO, MS, and Anne Chiang, MD, PhD, FASCO, prepared useful Practice Aids pertaining to small cell lung cancer for this CME/MOC/AAPA activity titled “Harnessing the Power of the Latest Clinical and Research Advances in SCLC: How to Accelerate Progress and Improve Patient Outcomes With Current and Emerging Therapies.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at https://bit.ly/46zyU93. CME/MOC/AAPA credit will be available until January 2, 2025.
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Harnessing the Power of the Latest Clinical and Research Advances in SCLC: How to Accelerate Progress and Improve Patient Outcomes With Current and Emerging Therapies
1. SCLC Treatment Algorithm1-3,a
Full abbreviations, accreditation, and disclosure information available at
PeerView.com/ZZA40
a
This algorithm was created by Aakash Desai, MBBS, MPH, and used with his permissions.
1. Paz-Ares L et al. ESMO Open. 2022;7:100408. 2. Paz-Ares L et al. ESMO 2021. Abstract LBA61. 3. NCCN Clinical Practice Guidelines in Oncology. Small Cell Lung Cancer. Version 2.2024.
https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf.
CT abdomen/pelvis, PET/CT scan (if needed), MRI brain, PFTs,
bone marrow biopsy (select cases), mediastinal staging (stage I-IIA)
Stage and Workup
Cancer confined to one hemithorax and regional lymph nodes (can be treated with single radiation field)?
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Limited-Stage Disease
Eligible for treatment of curative intent
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Extensive-Stage Disease
Stage III/IV disease; not eligible for treatment of curative intent
YES NO
STAGE I-IIA
STAGE IIB-IIIC
Pathologic
mediastinal
staging
Positive
Negative
Platinum-based
chemotherapy
+ concurrent RT
(PS 0-2)
or
± RT (PS 3-4 due
to SCLC)
JCOG 9104:
Concurrent RT vs
sequential RT
• mOS: 27.2
vs 19.7 mo
• HR: 0.70
Lobectomy + mediastinal LN
dissection or sampling
Platinum-based
chemotherapy
Platinum-based
chemotherapy
+
mediastinal RT
R0, N0
R0, N+
and/or
R1-2
Take into account PS, comorbidities, and age
Meta-analysis: PCI vs no PCI
RR of death HR: 0.84 (P = .01)
Prophylactic Cranial Irradiation in Patients Achieving Remission (ALL Stages)
PS ≤2 or ≥3 due to SCLC
PS ≥3 not due
to SCLC
Individualized
therapy in
consult with
palliative
medicine
1L: Chemo-immunotherapy
If ineligible for
immunotherapy,
use platinum-
based
chemotherapy
>6 mo CTFI
Relapse
Yes No
2L: Chemotherapy
2L: Chemotherapy
Carboplatin + etoposide + atezolizumab
with maintenance atezolizumab
IMpower133: Chemo + atezo vs chemo
• mOS: 12.3 vs 10.3 mo
• HR: 0.76
Carboplatin or cisplatin + etoposide +
durvalumab with maintenance durvalumab
CASPIAN: Chemo + durva vs chemo
• mOS: 12.9 vs 10.5 mo
• HR: 0.71
Rechallenge with original
platinum-based
chemotherapy (preferred)
Lurbinectedin (recommended)
Phase 2 basket trial: Single arm
• ORR: 35.2%
• mDOR: 5.1 mo
For complete treatment
recommendations and
regimens, refer to the
NCCN guidelines
Lurbinectedin (preferred)
Phase 2 basket trial: Single arm
• ORR: 35%
• mDOR: 5.1 mo
Topotecan (preferred)
Trial: Topotecan vs CAV
• ORR: 23.3% vs 18.3%
Clinical trials (preferred)
For complete treatment
recommendations and
regimens, refer to the
NCCN guidelines
Clinical trials (preferred)
T1-2, N0, M0
T3-4, N0, M0
T1-4, N1-3, M0
2. Immune-Related Adverse Events of Cancer Immunotherapies
Become Aware and Stay Vigilant
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZZA40
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/ZZA40
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/ZZA40
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 work-up: CXR, CT, pulse oximetry; for grade ≥2, may include infectious work-up
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/ZZA40
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