This document summarizes biologics and targeted therapy in the management of lung cancer. It discusses the different types and stages of lung cancer and molecular testing to identify targets for targeted therapies like EGFR and ALK inhibitors. Immunotherapy options for advanced NSCLC and extensive SCLC are also covered, including immune checkpoint inhibitors like pembrolizumab, atezolizumab, and cemiplimab. Comparative data on survival outcomes between chemotherapy and chemo-immunotherapy are presented. Limitations and challenges with targeted and immunotherapies are noted.

1. Biologics and targeted therapy
in the management of lung
cancer
Dr. Mohammad Zannatul Rayhan
Pulmonologist

2. —Prophet ‫ﷺ‬
"There is no disease that Allah
has created, except that He
also has created its treatment."
Sahih al-Bukhari
Vol. 7, Book 71, Hadith 582

3. New cases
130,000
Death
230,000
USA
Annually
Lung cancer

4. 1.8 million
Death due to lung cancer in 2020
World wide

5. Death
Lung cancer
Breast
Prostate
Colorectal
Brain
cancer

6. Diagnosed at
Metastatic stage
>50%

7. Survival is
improving
Screening and treatment advances:
targeted therapy and biologics

8. Types of lung cancer
Small cells Squamous cells
Adenocarcinoma Large cells
15% 25-30%
35-40% 10-15%
Types
Small cell
Non
small cell
Squamous
Non
squamous

9. Non small cell lung cancer stages
Stage I Stage II Stage III Stage IV
Small cell lung cancer stages
Limited Extensive

10. Molecular character
Spread and degree of
differentiation
Nature of malignancy
Health status
Treatment depends
Histopathology
ECOG etc.
Comorbidities
Staging and grading
Performance status
 Presence or absence of driver mutation
 Programmed death ligand-1 expression
(PD-L1)

11. Treatment of NSCLC
Platinum based
Chemotherapy
Different types
Radiation
Most appropriate if
possible
Surgery

12. Advanced NSCLC ?
Some of stage III and stage IV
•Targeted therapy
•Biologics(immunotherapy)

13. Targeted therapy
● Drugs that inhibit specific
molecules that play a
critical role in the growth
and survival of cancer
cells
● Given alone or with other
modalities of treatment

14. Finding target
Got it
Genetic mutation

15. Molecular target

16. Molecular testing technique
● Tissue PCR sequencing
● Tissue type allele PCR
sequencing
● Tissue next generation
sequencing
● Tissue immunohistochemistry
● Tissue RNA detection

17. EGFR TK mutation
● 15% USA, up to 62% in Asian people
● (Adenocarcinoma)
● Frequently in non-smoker
● Predictors of favorable outcome:
adenocarcinoma, women, non-smoker, Asian

18. EGFR TK Inhibitor
● First generation: Erlotinib, Gefitinib
● Second generation: Afatinib
● Third generation: Osimertinib

19. Comparison: survival outcome
● Osimertinib > Gefitinib or Erlotinib1
● Erlotinib > chemotherapy2,3,4
● Gefitinib > chemotherapy5
● Afatinib > chemotherapy6

20. Inter-comparison
● Osimertinib is frontline drug
● Afatinib have strongest disease outcome
but most side effects
● Gefitinib is most tolerated but have
inconsistent disease outcome
● Generally all are effective in positive EGFR
mutation
● Duration: until disease progression

21. Drugs: Tyrosine kinase Inhibitor(TKI)
● Osimertinib: Frontline EGFR TKI
● Dose:
Cell type Treatment
type
Genetic
changes
Dose Duration
NSCLC Adjuvant EGFR exon 19
deletion- or
exon 21 L858R
mutation
80 mg daily Until disease
progression
NSCLC
With mets
First time EGFR exon 19
deletion- or
exon 21 L858R
mutation
80 mg daily Until disease
progression
NSCLC with
mets
Previously
treated
T790M EGFR
mutation-
positive
80 mg daily Until disease
progression
NSCLC,adeno
With brain mets
EGFR
mutation-
positive
160 mg daily

22. ALK rearrangement
● 4% of NSCLC adenocarcinoma(USA)
● Non smoker
● Young
● Predict more response to ALK TKI
● Predict significant progression free survival

23. ALK TKI
● First generation: Crizotinib
● Second generation: Alectinib, Brigatinib,
Ensartinib, Ceritinib
● Third generation: Loratinib

24. ALK TK Inhibitor
● Preferred: Alectinib, Brigatinib, Loratinib
● Less preferred: Ceritinib, Crizotinib
● Duration: until disease progression

25. Other mutations
Mutation Choice of drug
ROS1 Crizotinib, Entrectinib
MET Capmatinib, Tepotinib
RET Selpercatinib, Pralsetinib
BRAF Dabrafenib, Trametinib
NTRK Larotrectinib, Entrectinib
KRAS Sotorasib, Adagrasib
HER2 Fam-trastuzumab deruxtecan

26. Common problems with targeted therapy
● Development of resistance ( by mutation e.g.
T790M mutation)
● Side effects of the drugs: commonly fatigue,
nausea, diarrhea. Some are life threatening
● Limited applicability: only used in specific
mutations
● Lack of lab facilities
● High cost
● Lack of long-term data

27. No mutation !!!
Advanced NSLC
Biologics

28. Biologics(Immunotherapy)
● Biologics, such as
monoclonal
antibodies, are
designed to target
specific proteins that
are overexpressed in
cancer cells

29. Cancer immunotherapy
Checkpoint

30. Programmed cell death ligand 1(PD L1)
● Determine need of immunotherapy
● By PD-L1 IHC, should be done in all patients
● Patients with PD-L1 expression ≥50% :
 biologics or
 a platinum-doublet chemotherapy+ biologics
● For patients with PD-L1 expression <50%:
 platinum-doublet chemotherapy+ biologics

31. Management of advanced NSCLC without a targetable mutation
-Cancer care Ontario guideline 12

32. Pembrolizumab
● Monoclonal antibody
● Immune checkpoint inhibitor(PD1)
● Doses:
 Stage III NSCLC : 200 mg every weekly
 Stage IV NSCLC( non squamous): 200mg every 3
weekly + combination chemotherapy first 4 cycle
F/B 200mg every 3 weekly
 Stage IV NSCLC( squamous): 200mg every 3 weekly
+ combination chemotherapy first 4 cycle F/B
200mg every 3 weekly
● Duration: until unacceptable side effects or disease
progression( 24 months or 35 cycles)

33. Pretreatment considerations
● Immune status: use with caution in autoimmune
disease
● Thyroid function test
● Prophylaxis of infection, infusion reaction,
emesis is not required.

34. Monitoring
● Complete blood count, electrolytes, renal
function test, liver function test, blood
glucose in every 3 weeks.

35. Atezolizumab
● Anti-PD-L1 Monoclonal Antibody
● Immune checkpoint inhibitor
● Doses:
 Stage IV NSCLC: 1200mg every 3 weekly +
combination chemotherapy first 4 cycle F/B
200mg every 3 weekly
● Duration: until unacceptable side effects or
disease progression ( 12 months)

36. Cemiplimab
● Anti-PD1 Monoclonal Antibody
● Immune checkpoint inhibitor
● Doses:
 Stage IV NSCLC: 350mg every 3 weekly +
combination chemotherapy first 4 cycle F/B
200mg every 3 weekly
● Duration: until unacceptable side effects or
disease progression ( 25 months)

37. PD-L1 IHC can’t be done!!!
● Nivolumab plus Ipilimumab, with or without
chemotherapy
● Nivolumab:
 PD1 inhibitor
 Dose: 240 mg once every 2 weeks or 480 mg once every
4 weeks until disease progression or unacceptable
toxicity.
● Ipilimumab:
 Cytotoxic T cell associated protein 4 inhibitor
 Dose: 1 mg/kg once every 6 weeks until disease
progression or unacceptable toxicity.

38. Comparison
● Chemo immunotherapy Vs chemotherapy alone
● Median survival was better in
Chemoimmunotherapy
● Cemiplimab with chemo Vs chemo alone
(22 versus 13 months)7

39. Comparison
● Immunotherapy alone Vs Chemoimmunotherapy
● No direct comparison trial but indirect evidence
● Median survival was better in
Chemoimmunotherapy
(9.6 versus 7.1 months)8

40. Comparison
● Immunotherapy Vs Chemotherapy
● Tremelimumab + Durvalumab Vs Chemotherapy
● Median survival was better in immunotherapy
(15 versus 11 months)9

41. Common problems with biologics
● Increase risk of infection: bacterial, viral,
fungal( checkpoint inhibitor does not cause
immune suppression)
● High cost
● Infusion reaction
● Immunogenicity: may provoke autoimmunity
● Increased risk of certain types of cancer
● Route of administration

42. SCLC
• Limited:
Chemo-radiotherapy
• Extensive:
Immunotherapy plus
platinum-etoposide

43. Extensive SCLC
● No brain metastasis: anti-PDL1 antibody+
platinum-etoposide
● Brain metastasis with no symptoms: anti-PDL1
antibody+ platinum-etoposide WBRT
● Brain metastasis: WBRT

44. Anti-PDL1 antibody
● Atezolizumab
● Durvalumab

45. Atezolizumab
● Anti-PD-L1 Monoclonal Antibody
● Immune checkpoint inhibitor
● Doses:
 Extensive SCLC: 1200mg every 3 weekly +
combination chemotherapy first 4 cycle F/B
200mg every 3 weekly
● Duration: until unacceptable side effects or
disease progression

46. Durvalumab
● Anti-PD-L1 Monoclonal Antibody
● Immune checkpoint inhibitor
 Doses: Extensive SCLC: 1200mg every 3 weekly +
combination chemotherapy first 4 cycle F/B
200mg every 4 weekly
● Duration: until unacceptable side effects or
disease progression

47. Comparison
● Chemo immunotherapy Vs chemotherapy alone
● Median survival was better in
chemoimmunotherapy
● Atezolizumab with chemo Vs chemo with palcebo
(12.3 versus 10.3 months)10
Durvalumab with chemo Vs chemotherapy
(13 versus 10.3 months)11

48. Summary
Lung
cancer
NSCLC
Operable
± Other
modalities
Inoperable
Mutation
Targeted
therapy
No mutation
PDL1 expression
<50%
expression
Chemo-
immunotherapy
Immunotherapy
>50%
expression
Extensive
Chemo-immunotherapy
Not extensive
Immunotherapy
SCLC
Extensive
Chemo-
immunotherapy
Limited
Chemo-radiotherapy
Or,

49. At last!!!
Don’t forget!!!
Smoking cessation
Screening with low dose CT

50. CREDITS: This presentation template was created
by Slidesgo, including icons by Flaticon and
infographics & images by Freepik
Thanks!
Do you have any questions?
Zannatulrayhan@gmail.com
+880 1557033829
https://www.facebook.com/zannatul.rayhan

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