The document discusses various targeted therapies used in oncology including monoclonal antibodies, small molecule inhibitors, and tyrosine kinase inhibitors. It provides information on drug indications, mechanisms of action, FDA approvals, and common adverse effects for several targeted agents such as palbociclib, bortezomib, imatinib, crizotinib, ceritinib, osimertinib, and vemurafenib. The document is intended to educate medical practitioners on modern targeted therapies for cancer treatment.

1. Dr. Rajib Bhattacharjee
Apollo Gleneagles Hospital,
kolkata

3. Monoclonal Antibodies Small molecule agent

4. ENZYME
INHIBITORS
PARP Inhibitors
Fernesyl
Transferase
inhibitors
CDK Inhibitors
Histone
Deacetylase
Inhibitors
Proteasome
Inhibitors
EMP
Dehydrogenase
inhibitors
TYROSINE KINASE
INHIBITORS
Single
Receptor TKI
Erlotinib
Multireceptor
TKI
Sunitinib
Non
Receptor TKI
Imatinib

7. Defined as the situation when a mutation in either of two genes
individually has no effect, but combining the mutations lead to death.

16. P
A
L
O
M
A
1

19. Conclusion: PALOMA-2 expands and confirms the
significant clinical benefit and safety of P+L in
ER+/HER2– ABC pts who had not received prior
systemic therapy for their advanced disease.

20. Conclusion: Palbociclib plus Fulvestrant improves
PFS and was well tolerated in this study.

21. Palbociclib is indicated for the treatment of
HR-positive, HER2-negative advanced or
metastatic breast cancer in combination
with:
 An aromatase inhibitor as initial endocrine
based therapy in postmenopausal women; or.
 Fulvestrant in women with disease
progression following endocrine therapy

26. FDA approved indications
 Third-line treatment of
multiple myeloma
(2003) and expanded
to first-line treatment
in 2008.
 Mantle cell lymphoma
(2006).
 First-line in multiple
myeloma with
Melphalan &
Prednisolone(VMP).
Adverse effects
 Thrombocytopenia
 Peripheral
Neuropathy
Possible use in Solid tumors
•NSCLC
•RCC
•Breast carcinoma

27. Indications
Relapsed or refractory
Multiple Myeloma 2-4th
line
 Monotherapy: 20/27 or
20/56 schedule
 Dual regimen: with
Dexamethasone
 Triple combination: with
Lenalidomide &
Dexamethasone (Aspire
Trial)
Toxicities
 Hematologic –
Neutropenia,
Thrombocytopenia
 Cardiac – CHF, IHD
 Pulm HTN
 Hepatic – elevation of
transaminase
 Peripheral neuropathy

29. Receptor TKIs
 EGFR – Geftinib.
Erlotinib, Afatinib,
Osimertinib
 HER2 – Lapatinib
 VEGFR – Sunitinib,
Sorafenib, Pazopanib,
Axitinib
 PDGFR - Imatinib
Non receptor TKI
 ALK - Crizotinib
 BCR-ABL - Imatinib
 KIT – Imatinib, Sunitinib
 TORC1 - Sirolimus
 mTOR - Everolimus
 BRAF - Vemurafenib
 BTK - Ibrutinib
 RET - Cabozantinib
 MEK - Trametinib
 JAK2 – Ruxolitinib
 SRC - Bosutinib

32.  Imatinib
 Dasatinib
 Nilotinib
 Bosutinib
 Ponatinib

35. Indications
 CML - Ph+
 ALL
 GIST
 Darmatofibrosarcoma
protuberance
 MDS/MPS
 Hypereosinophillic
syndrome
 Mastocytosis
Adverse effects
 Edema
 Neutropenia
 Nausea
 Muscle cramps
 Thrombocytopenia
 Rash, fatigue, diarrhea
 Headache, arthralgia,
 Myalgia

38. 1st generation 2nd generation 3rd generation
Crizotonib Ceritinib Lorlatinib
Alectinib
Brigatinib

39. Crizotinib is active both in 1st as well as 2nd line

40. 2. Poor CNS Penetration
Toxicities
Visual disorders
GI effects
Edema
Fatigue
Elevated liver
enzymes
QT Prolongation
Pneumonitis

41. Indications
 In April 2014, Ceritinib
received accelerated
approval for patients with
ALK-positive metastatic
NSCLC whose disease
has progressed or who
are intolerant to crizotinib
 On May 26, 2017, the
U.S. F.D.A granted regular
approval to ceritinib for
metastatic ALK-positive
NSCLC
Adverse Effects
 GI Effects
 Anemia
 Elevated liver enzymes
 Fatigue
 Pneumonitis

46. Indications
 In ALK +ve advanced
NSCLC – after
progression
/intolerance to
Crizotinib (FDA 2015)
 Upfront setting (FDA
2017)
Adverse Effects
 Constipation
 Elevated CPK
 Fatigue, myalgia
 Fluid retention
 Elevated liver enzymes
 Bradycardia
 Pneumonitis

52. Indication
1st line drug in
metastatic
NSCLC with
sensitising EGFR
mutation
Adverse Effects
 Elevated liver enzymes
 GI Effects
 Skin reaction
 Proteinuria
 Anorexia
 Asthenia
 Interstitial lung disease
 Keratitis, Dry eye

56. Indication
 Metastatic NSCLC with
sensitising EGFR
mutations receiving 1st
line, maintenance, or
≥2nd line treatment
 1st line treatment in
locally advanced,
unresectable, or
metastatic pancreatic
cancer
Adverse Effects
 Rash
 Fatigue
 Diarrhoea
 Anorexia
 Dyspnoea, cough
 Nausea , vomiting
 Infection,
 Conjunctivitis, keratitis
 Elevated liver enzymes
 IHD
 ILD

67. Adverse Effects
 Diarrhea, stomatitis
 Acneiform rash/dermatitis
 Paronychia, dry skin
 Decreased appetite
 Loss of weight
 Cystitis
 Epistaxis, rhinorrhea
 Elevated liver enzymes
 Pyrexia

77.  Lymphopenia
 Thrombocytopenia
 Anemia
 Diarrhea
 Rash
 Neutropenia
 Dry skin
 Hyponatremia
 Nail toxicity
 Venous
thromboembolism
 Pneumonia
 Interstitial lung
disease/pneumonitis
 QTc prolongation
 Cardiomyopathy
 Keratitis
Adverse Effects