Chair, Taofeek K. Owonikoko, MD, PhD, Carl M. Gay, MD, PhD, and Ticiana Leal, MD, prepared useful Practice Aids pertaining to small cell lung cancer for this CME/MOC/NCPD/AAPA activity titled “Progress on the Path to Improving Outcomes in the Treatment of SCLC: Making the Most of Current Standard-of-Care Therapies and Exploring New Promising Research.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/AAPA information, and to apply for credit, please visit us at https://bit.ly/3pijZiM. CME/MOC/NCPD/AAPA credit will be available until July 4, 2024.

1. SCLC Treatment Algorithm1-3
Full abbreviations, accreditation, and disclosure information available at
PeerView.com/WFE40
1. Created by Aakash Desai, MBBS, MPH. Used with permission from the author. 2. Paz-Ares L et al. ESMO Open. 2022;7:100408.3. Paz-Ares LG et al. ESMO 2021. Abstract LBA61.
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)?
!"#"$%&'($)*%
?#*@*&#($2,'$+'(%+3(-+$,2$0"'%+*)($*-+(-+
Limited-Stage Disease
Eligible for treatment of curative intent
%4$%5("6%'($)*%
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
JCOG 9104:
Concurrent RT vs
sequential RT
• mOS: 27.2
vs 19.7 mo
• HR, 0.70
Lobectomy +
mediastinal LN dissection
Platinum-based
chemotherapy
Platinum-based
chemotherapy
+
mediastinal RT
pT1-2,
N0-1,
R0
N2
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 ≤1 or ≥2 due to SCLC
PS ≥2 due to
comorbidities
BSC in consult
with palliative
medicine
1L: Chemo-immunotherapy
If ineligible for
immunotherapy,
use platinum-
based
chemotherapy
>6 mo treatment-
free interval?
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, 0.70
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
PMB1183-B005014: Single arm
• ORR: 35%
• mDOR: 5.1 mo
CAV
Lurbinectedin (preferred)
PMB1183-B005014: Single arm
• ORR: 35%
• mDOR: 5.1 mo
Topotecan (preferred)
Trial: Topotecan vs CAV
• ORR: 23.3% vs 18.3%
Clinical trials (preferred)
CAV
cT1-2, N0, M0
T1-2, N1, M0
T3-4, Nx, M0

2. The Immunotherapy Era in SCLC: Approved Treatments
and Immune-Related Adverse Event Management
Full abbreviations, accreditation, and disclosure information available at PeerView.com/WFE40
Currently Approved PD-L1–Blocking Antibodies in Immuno-Chemotherapies, Supporting Evidence, and Practical Guidance
Durvalumab1,2
Granted FDA approval in
combination with
etoposide and either
carboplatin or cisplatin as
first-line treatment of
patients with ES-SCLC
on March 27, 2020
Indicated in combination with etoposide and either
carboplatin or cisplatin as first-line treatment of
adult patients with ES-SCLC
Indication
1,500 mg every 3 weeks prior to chemotherapy
in combination with etoposide and either carboplatin
or cisplatin, then every 4 weeks as a single agent
Dosing2
CASPIAN: A Randomized, Controlled, Open-Label, Phase 3 Trial3-6
Most Common AEs
(All Grades)1
• Nausea (34%)
• Fatigue/asthenia (32%)
• Alopecia (31%)
Atezolizumab7,8
Granted FDA approval in
combination with
carboplatin and
etoposide for first-line
treatment of adult
patients with ES-SCLC
on March 18, 2019
Indicated in combination with carboplatin and etoposide
for first-line treatment of adult patients with ES-SCLC
Indication
1,200 mg every 3 weeks prior to chemotherapy with
carboplatin and etoposide; 840 mg every 2 weeks,
1,200 mg every 3 weeks, or 1,680 mg every 4 weeks following
completion of 4 cycles of carboplatin and etoposide
Dosing7
IMpower33: A Double-Blind, Placebo-Controlled, Phase 3 Trial9
Most Common AEs
(All Grades)7
"
• Fatigue/asthenia
• Nausea
• Alopecia
• Constipation
• Diarrhea
• Decreased appetite
Platinum-etoposide
(n = 269)
Durvalumab +
Platinum-etoposide
(n = 268)
156 (58)
182 (68)
5.1 (4.8-5.3)
5.1 (4.9-5.3)
Median duration of
response,
mo (95% CI)
10.5 (9.3-11.2)
12.9 (11.3-14.7)
Median OS,
mo (95% CI)
5.4 (4.8-6.2)
5.1 (4.7-6.2)
Median PFS,
mo (95% CI)
a
Objective response by investigator review per RECIST 1.1 is defined as patients with complete
response or partial response on at least one visit (unconfirmed responses); for confirmed
responses, a confirmatory scan was required ≥4 weeks after the initial response.
Placebo
(n = 202)
Atezolizumab
(n = 201)
130 (64.4)
121 (60.2)
3.9 (2.0-16.1)
4.2 (1.4-19.5)
Median duration of
response,
mo (range)c
Confirmed objective
response, n (%)a
Confirmed objective
response, n (%)b
10.3 (9.3-11.3)
12.3 (10.8-15.9)
Median OS,
mo (95% CI)
4.3 (4.2-4.5)
5.2 (4.4-5.6)
Median PFS,
mo (95% CI)
b
Assessed in patients in the ITT population who had measurable disease at baseline. Defined
as confirmed complete response or partial response by investigator review per RECIST 1.1.
c
Assessed in patients who had a confirmed objective response. Defined as the time from first
occurrence of a documented objective response to the time of disease progression as
determined by the investigator (according to RECIST) or death from any cause, whichever
occurred first.

3. The Immunotherapy Era in SCLC: Approved Treatments
and Immune-Related Adverse Event Management
Full abbreviations, accreditation, and disclosure information available at PeerView.com/WFE40
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 Barré
Myelopathy
Encephalitis
Myasthenia
Musculoskeletal
Arthritis
Dermatomyositis
Immune-Related Adverse Events (irAEs)10

4. General Recommendations for Treating irAEs11-14
Increasing
Intensity
of
Treatment
Required
Increasing Grade of irAE
Managed in Outpatient/Community Setting Generally Requires Hospital Admission
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
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
intravenous steroids
The Immunotherapy Era in SCLC: Approved Treatments
and Immune-Related Adverse Event Management
Full abbreviations, accreditation, and disclosure information available at PeerView.com/WFE40

5. The Immunotherapy Era in SCLC: Approved Treatments
and Immune-Related Adverse Event Management
Full abbreviations, accreditation, and disclosure information available at PeerView.com/WFE40
 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?11,15
 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)

6. The Immunotherapy Era in SCLC: Approved Treatments
and Immune-Related Adverse Event Management
Full abbreviations, accreditation, and disclosure information available at PeerView.com/WFE40
1. Imfinzi (durvalumab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761069s033lbl.pdf. 2. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-extensive-stage-small-cell-lung-cancer.
3. Paz-Ares L et al. Lancet. 2019;394:1929-1939. 4. Goldman JW et al. Lancet Oncol. 2021;22:51-65. 5. Paz-Ares L et al. ESMO Open. 2022;7:100408. 6. Paz-Ares LG et al. ESMO 2021. Abstract LBA61. 7. Tecentriq (atezolizumab) Prescribing Information. https://www.accessdata.fda.gov/
drugsatfda_docs/label/2023/761034s049s051lbl.pdf. 8. https://www.fda.gov/drugs/drug-approvalsand-databases/fda-approves-atezolizumab-extensive-stage-small-cell-lung-cancer. 9. Horn L et al. N Engl J Med. 2018;379:2220-2229. 10. Champiat S et al. Ann Oncol. 2016;27:559-
574. 11. Brahmer JR et al. J Clin Oncol. 2018;36:1714-1786. 12. https://www.esmo.org/content/download/124130/2352601/1/ESMO-Patient-Guide-on-Immunotherapy-Side-Effects.pdf. 13. https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf.
14. Puzanov I et al. J Immunother Cancer. 2017;5:95. 15. Provided courtesy of Marianne Davies, DNP, ACNP, AOCNP, FAAN, 2021; adapted from AIM with Immunotherapy, NCCN, and CTCAE. 16. https://ascopubs.org/doi/full/10.1200/JCO.21.01440.
17. https://www.esmo.org/content/download/124130/2352601/1/ESMO-Patient-Guide-on-Immunotherapy-Side-Effects.pdf. 18. https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf.
19. https://www.sitcancer.org/research/cancer-immunotherapy-guidelines/irae/immune-checkpoint-inhibitor-related-adverse-events.
Additional Guideline Recommendations for Treating irAEs16-19

7. Lurbinectedin: The Newest FDA-Approved
Second-Line Treatment Option in SCLC
Full abbreviations, accreditation, and disclosure information available at PeerView.com/WFE40
Lurbinectedin (Selective Inhibitor of Oncogenic Transcription)1,2
Granted accelerated
FDA approval
on June 15, 2020
based on overall
response rate and
duration of response
Indicated for the treatment of adult patients with
metastatic SCLC with disease progression on or
after platinum-based chemotherapy
Indication
3.2 mg/m2
via intravenous infusion every 21 d
(consider premedication with corticosteroids
and serotonin antagonists)
Dosing2
Mechanism of Action1
• Category 2A other recommended regimen following first-line platinum-based
chemotherapy
• For patients with ECOG PS 0-2 (consider dose reduction or growth factor support
for patients with ECOG PS 2)
NCCN Guidelines: Second-Line and Beyond Therapy3
ORR by Investigator Assessment1
Most Common Grade 3/4 AEs1
Other common adverse events include lymphopenia, fatigue, increased creatinine, increased
alanine aminotransferase, increased glucose, nausea, decreased appetite, musculoskeletal
pain, decreased albumin, constipation, dyspnea, decreased sodium, increased aspartate
aminotransferase, vomiting, cough, decreased magnesium, and diarrhea
Neutropenia
46%
Anemia
9%
Leukopenia
29%
Thrombocytopenia
7%
All patients
35.2%
Chemotherapy-free
interval ≥90 d
45.0%
Chemotherapy-free
interval <90 d
22.2%
Tumor
CCL2
Induction of
apoptosis
Monocyte
CCL2
CXCL8
VEGF
Reduced
cancer-related
inflammation
TAM
Inhibition of
cell migration
LURBINECTEDIN
• Synthetically produced
agent, originally
derived from
Ecteinascidia turbinata
• A selective inhibitor of
oncogenic transcription
1. Zepzelca (lurbinectedin) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213702s004lbl.pdf. 2. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-lurbinectedin-metastatic-small-cell-lung-cancer.
3. https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf.

8. LUNGevity Foundation: Small Cell Lung Cancer
Resource Compendium
Full abbreviations, accreditation, and disclosure information available at PeerView.com/WFE40
The following pages include information for patients with lung cancer for use as a printable resource
lungevity.org
Through research, advocacy, and community, LUNGevity is transforming
what it means to be diagnosed and live with lung cancer
www.lungevity.org/order-materials
LUNGevity educational materials order form for providers:
.

9. LUNGevity Foundation: Small Cell Lung Cancer
Resource Compendium
1 What Is Small Cell Lung Cancer (SCLC)? The Stages of SCLC
• Lung cancer staging describes where the cancer is located,
if and where it has spread, and whether it is affecting other
parts of the body
• Treatments are available for every stage
Extensive-stage: cancer has spread more widely throughout the
lung, to the other lung, to lymph nodes on the other side of the
chest, or to distant organs
Limited-stage: cancer is only in one side of the chest: one lung,
the tissues between the lungs, and nearby lymph nodes only
Most commonly used system: 2 stages
3
2
4
Diagnosis of SCLC Treatment Options
Many different tests are used to diagnose SCLC, including
• Biopsies: tests in which small
amounts of tissue are removed
for examination to find out if a
person has lung cancer and, if
so, which type
• Imaging: tests that create
pictures of the inside of the
body by x-rays, magnetic
fields, sound waves, or
radioactive particles
Currently approved treatment options for SCLC include:
• Surgery
• Radiation therapy
• Chemotherapy
• Immunotherapy
In addition, several new types of treatment are being studied
for SCLC. These are available through clinical trials.
https://sclc.lungevity.org/sclc/about-small-cell-lung-cancer
• SCLC is one of the two major types of lung cancer
• It accounts for about 15% of all lung cancers
• It is most often found in people with
a smoking history
• SCLC derives its name from
the way the cancer cells look
under a microscope
Trachea
Bronchoscope
or endoscope
Throat
Lymph nodes
Lung
Bronchi
Small cell
lung cancer
(cells under
microscope)

10. Booklets: www.LUNGevity.org/booklets
In booklet 1, you will learn
• What SCLC is
• What lung cancer staging is
• The stages of SCLC
What is small cell lung
cancer (SCLC)?
One-Page Fact Sheets
In booklet 2, you will learn
• Types of tests doctors do to find SCLC
• What happens during imaging tests
• Why doctors do biopsies and what happens
during them
• Other ways doctors learn about your health
In booklet 3, you will learn
• How you and your doctor will decide on a treatment plan
• What the treatment options are for SCLC
• Common side effects of treatment
Comprehensive
booklet
Questions to ask your
doctor to better
understand SCLC, stage,
and treatment options
Resources and support
for SCLC
2
Educational Materials and Supporting Resources
The Small Cell Lung Cancer Patient Gateway is a tailored portal for people with SCLC to learn more about
treatment for SCLC, connect to experts and SCLC patient communities, and access educational resources
Find a Specialist Find a Clinical Trial Blog and Forum
Find Your Community
3
1
2
LUNGevity Foundation: Small Cell Lung Cancer
Resource Compendium