Small cell lung cancer (SCLC) is an aggressive type of lung cancer linked to smoking. It is a neuroendocrine tumor that is highly sensitive to chemotherapy and radiation initially but often recurs. The two main types are limited stage, confined to one lung, and extensive stage, which has spread. Platinum-based chemotherapy is standard and some patients receive prophylactic brain radiation. For extensive stage with response to chemotherapy, radiation to the chest improves survival. Topotecan helps with symptoms for relapsed SCLC compared to multi-agent chemo. Immunotherapy like pembrolizumab shows benefit for some after standard therapies fail.

1. S.C.L.C
B Y
D R . H A T E M E L E T R I P Y

2. Lung SCLC
• Mostly caused by cigarette smoke
• Decreased incidence 20% to 13%
• Is a neuroendocrine tumor
• Most aggressive type and widely disseminated
• Highly sensitive to chemotherapy and radiotherapy, but recurrence is
common

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4. Pathology
• Virtually all SCLCs are immunoreactive for keratin and epithelial
membrane antigen because of their epithelial cellular origin. express
thyroid transcription factor-1 (TTF1), which can help distinguish SCLC
from neuroendocrine cancers originating in an organ other than the
lung.
• Markers of neuroendocrine differentiation can be found in
approximately 75 percent of SCLCs include synaptophysin,
chromogranin, and CD56 (neural cell adhesion molecule [NCAM]).
Expression of neuron-specific enolase (NSE), dopa decarboxylase,
calcitonin, gastrin releasing peptide (GRP), and insulin-like growth
factor-I (IGF-1) is also commonly observed.

5. Staging
• Limited disease – Tumor confined to the ipsilateral hemithorax and
regional nodes able to be included in a single tolerable radiotherapy
port (corresponding to Tumor, Node, Metastasis [TNM] stages I
through IIIB.
• Extensive disease – Tumor beyond the boundaries of limited disease
including distant metastases, malignant pericardial, or pleural
effusions, and contralateral supraclavicular and contralateral hilar
involvement.

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7. Chemotherapy
• combination chemotherapy with four cycles of a platinum-based
regimen.
• A meta-analysis that included 663 patients in four trials compared the
efficacy of cisplatin-based versus carboplatin-based regimens in SCLC
Overall, response rate, progression-free survival, and overall survival
were similar with cisplatin-based and carboplatin-based regimens.

8. Rossi et al, J Clin Oncol. 2012;30(14):1692. Epub 2012 Apr 2

10. Why THORACIC RADIATION THERAPY??
• Two large meta-analyses have reported benefit to the use of
combined chemotherapy and thoracic RT, both in regards to local
recurrence and survival.
• One meta-analysis, which included 11 randomized studies, found that
the addition of thoracic RT was associated with an absolute
improvement in local control of 23 percent (two-year local control
rate 47 versus 24 percent).

11. SCLC-LD: CHEMO-RADIOTHERAPY
Metaanalysis of 13 studies
SURVIVAL
Chemotherapy+ RT (n=1111)
Chemotherapy (n=992)
Years
Pignon et al. 1992

12. PROPHYLACTIC CRANIAL IRRADIATION
• Prophylactic cranial irradiation following chemotherapy has been
demonstrated to decrease the incidence of symptomatic brain
metastases and increase overall survival in patients with LS-SCLC.

13. LD-SCLC Prophylactic
cranial irradiation
Months
%cerebralrelapse
Arriagada et al 1995

14. Extensive-stage small cell lung cancer

15. Platinum-based combinations
• Platinum-based combinations are the standard of care for the initial
systemic therapy in patients with SCLC. Data suggest the addition of
atezolizumab to a backbone of carboplatin and etoposide improves
outcomes.

17. https://www.tecentriq-hcp.com/sclc/clinical-data-efficacy/study-design.html

18. N Engl J Med. 2018;379(23):2220. Epub 2018 Sep 25

19. N Engl J Med. 2018;379(23):2220. Epub 2018 Sep 25

20. N Engl J Med. 2018;379(23):2220. Epub 2018 Sep 25

21. Duration of treatment
• The optimal duration of induction chemotherapy for patients with
SCLC is not well defined; our general approach is to give four to six
cycles. When atezolizumab is administered, it is continued until
progression of disease or unacceptable toxicity.

22. RADIATION THERAPY AFTER RESPONSE TO
CHEMOTHERAPY
Thoracic radiation therapy
• For patients with ES-SCLC who have had a favorable response to their
initial chemotherapy and who have residual disease limited to the
chest, thoracic RT is associated with improved overall survival (OS).
• There is no evidence that thoracic RT improves survival in those
without residual thoracic disease by computed tomography (CT).

23. European multicenter phase lll trial

24. • OS at one year for the entire cohort was not significantly increased in
those given thoracic RT compared with chemotherapy alone (33
versus 28 percent, hazard ratio [HR] 0.84, 95% CI 0.69-1.01, p = 0.07).
• In a secondary analysis, the survival curves diverged after longer
follow-up, and subsequent survival was significantly better for those
receiving thoracic RT (two-year OS rate 13 versus 3 percent, p =
0.004).
• Progression-free survival (PFS) was significantly better for patients
receiving thoracic RT (24 versus 7 percent at six months, HR 0.73, 95%
CI 0.61-0.87).

27. PCI in ED-SCLC
Multicenter RCT by EORTC
286 patients with ED-SCLC achieving any response to chemotherapy
Median OS increased by 1.3 months (5.4 months in no PCI to 6.7 months in PCI; p = 0.003)
OS at 1 year increased from 13.3% to 27.1%
Decreased symptomatic brain metastases from 41.3% to 16.8% (p < 0.001)
Slotman B, N Engl J Med 2007; 357: 664-672

28. https://www.nccn.org version 1.2019 s.c.l.c

29. Topotecan
• This single agent has been shown to increase survival compared with
best supportive care (BSC) and results in greater symptom
management relative to a multiagent regimen.
Survival in weeks.
Regimen:
----Hycamtin; - - - 5 CAV.

30. In Phase lll Trial 141 patients randomly assigned to oral topotecan (2.3 mg/m2 daily
for five days every three weeks) or BSC, topotecan was associated with improved OS
(26 versus 14 weeks) .Patients on topotecan also experienced slower quality of life
deterioration and improved symptom control.

31. Subgroup analysis of survival according to the stratification factors of sex,
performance status (PS), time to progression from prior therapy, and
presence of liver metastases.

32. Refractory and Relapsed S.C.L.C
Data from CheckMate 032 open-label, phase 1/2 trial
In the initial treatment arms, pts with advanced SCLC and disease
progression after prior PLT-CT were assigned to :
nivo (3 mg/kg Q2W; n = 98) or nivo 1 + ipi 3 (1 mg/kg and 3 mg/kg
Q3W x 4, then nivo 3 Q2W; n = 61)

35. Phase 2 study of pembrolizumab in advanced
(SCLC): KEYNOTE-158
• 107 patients with SCLC who had previously been treated with
standard therapy, objective response rates were 19 percent overall,
36 percent in patients with PD-L1-positive tumors, and 6 percent in
PD-L1-negative tumors.
• Median PFS was 2.0 months in all patients, 2.1 months in those with
PD-L1-positive tumors, and 1.9 months in those with PD-L1-negative
tumors.

36. Thank you