2. Outline
Brentuximab as first line for Hodgkin lymphoma; first line for peripheral T-cell
lymphoma
Brigatinib for NSCLC with positive ALK previously treated with crizotinib
Lenvatinib for unresectable NSCLC
Osimertinib as first line for locally advanced or metastatic NSCLC with positive EGFR
Eribulin for progressive locally advanced or metastatic breast cancer
3. Brentuximab as first line
for Hodgkin lymphoma;
first line for peripheral
T-cell lymphoma
4. Brentuximab
• Antibody Drug Conjugate (ADC) that delivers an antineoplastic agent that results in apoptotic cell
death selectively in CD30-expressing tumor cells
• Brand label : Adcetris
• Class of agents : antibody drug conjugate (ADC)
• Labeled indications
• Anaplastic large cell lymphoma (primary cutaneous), relapsed
• Anaplastic large cell lymphoma (systemic), previously untreated
• Anaplastic large cell lymphoma (systemic), relapsed
• Hodgkin lymphoma, previously untreated
• Hodgkin
5. Brentuximab
Recommended dosages
Previously untreated : 1.2 mg/kg (max 120
mg) every 2 weeks
Relapsed or refractory : 1.8 mg/kg (max 180
mg) every 3 weeks
Administration
Intravenous, each 50 mg vial with 10.5 sterile
water for injection resulting in a concentration of
5 mg/ml
Use within 24 hours of initial reconstitution
6. Approval of Use
US (FDA)
2011: relapse refractory Hodgkin
lymphoma, relapse refractory
systemic anaplastic large cell
lymphoma, maintenance for
Hodgkin lymphoma after ASCT
2017: relapse refractory cutaneous
T-cell lymphoma
2018: first line Hodgkin lymphoma,
first line peripheral T-cell
lymphoma
Europe (EMA)
2012: relapse refractory Hodgkin
lymphoma, relapse refractory
systemic anaplastic large cell
lymphoma, maintenance for
Hodgkin lymphoma after ASCT
2017: relapse refractory cutaneous
T-cell lymphoma
2018: first line Hodgkin lymphoma,
first line peripheral T-cell
lymphoma
Indonesia (BPOM)
2017: relapse refractory Hodgkin
lymphoma, relapse refractory
systemic anaplastic large cell
lymphoma
2019: relapse refractory cutaneous
T cell lymphoma
7.
8.
9.
10. Pivotal Studies (1)
No Studies Study
phase
Study design Result
1 SGN35-003
Subject:
Relapsed or refractory
Hodgkin lymphoma
after autologous stem-
cell transplantation
As:
Salvage, monotherapy
2 Multinational,
open-label
n=102
Progression-free survival
Brentuximab vedotin: 9.3 mo (95% CI 1.2-36.4)
Overall survival
Brentuximab vedotin: 40.5 mo (95% CI 28.7-not
estimable)
Duration of response
6.7 mo
CR: 34%
PR: 40%
Grade of recommendation: 2B
11. Pivotal Studies (2)
No Studies Study
phase
Study design Result
2 SGN35-004
Subject:
Relapsed or refractory
systemic anaplastic
large-cell lymphoma
As:
Salvage, monotherapy
2 Multinational,
open-label
n=58
Progression-free survival
Brentuximab vedotin: 13.3 mo (95% CI 6.9-NE)
Overall survival
Brentuximab vedotin: median not reached (95%CI
21.3-NE)
Duration of response
12.6 mo (95%CI 5.7 to NE)
CR: 57%
PR: 29%
Grade of recommendation: 2B
NE: not estimable
12. Pivotal Studies (3)
No Studies Study
phase
Study design Result
3 ALCANZA
Subject:
Relapsed or refractory
cutaneous T-cell
lymphoma
As:
First line
3 International,
open-label,
randomized,
multicentre
n=131
Progression-free survival (EMA criteria)
Brentuximab vedotin: 16.7 mo
Physician choice: 3.5 mo
HR 0.270 (95%CI 0.169-0.430; p<0.0001)
Progression-free survival (FDA criteria)
Brentuximab vedotin: 17.2 mo
Physician choice: 3.5 mo
HR 0.181 (95%CI 0.101-0.324; p<0.0001)
Response (ORR4)
Brentuximab vedotin: 56.3%
Physician choice: 12.5%
Grade of recommendation: 2C
NE: not estimable
ORR4: objective global response lasting at least 4 mo
13. Pivotal Studies (4)
No Studies Study
phase
Study design Result
4 AETHERA
Subject:
Unfavourable-risk
relapsed or primary
refractory classic
Hodgkin’s lymphoma
who had undergone
ASCT
As:
Salvage
3 Randomised,
double-blind,
placebo-
controlled
n=131
Hazard ratio
HR 0.57 (95%CI 0.40-0.81; p=0.0013)
Grade of recommendation: 3B
14. Brigatinib
• Brand label : Alunbrig
• Class of agents : targeted therapy, ALK inhibitor
• Labeled indications
• Non-small cell lung cancer, metastatic (ALK-positive)
• Dosage : 90 mg once daily for 7 days; if tolerated, increase dose to 180 mg once daily
• Off-label indications:
• Non-small cell lung cancer, advanced (initial ALK-inhibitor therapy)
• Dosage : 90
15. Briganitib
Recommended dosages
90 mg once daily for 7 days; if tolerated, increase
dose to 180 mg once daily
Administration
Oral, with or without fodd, swallow tablets
whole; do not crush or chew
16. Approval of Use
US (FDA)
April 28th, 2017: ALK+ NSCLC in
previously treated with crizotinib
Europe (EMA)
September 20th 2018: ALK+ NSCLC
in previously treated with crizotinib
Indonesia (BPOM)
On registration process
17.
18. Pivotal Studies (1)
No Studies Study
phase
Study design Result
1 ALTA Trial
Subject:
Non-small cell lung
cancer previously
treated with crizotinib
As:
Salvage
2 Open-label,
randomized,
multicenter,
international
n=222
Progression-free survival
Brigatinib: 16.7 mo (95% CI 1.2-36.4)
Overall survival
Brigatinib: not reached
22. • In 2018, international, multicentre, randomised, open-label, non-inferiority trial
(REFLECT) conducted in 954 patients with previously untreated, metastatic or
unresectable HCC.
• Patients were randomised (1:1) to receive lenvatinib (12 mg orally once daily for patients
with a baseline body weight of ≥60 kg and 8 mg orally once daily for patients with a
baseline body weight of <60 kg) or sorafenib (400 mg orally twice daily).
23. RESULTS
• REFLECT demonstrated that lenvatinib was
non-inferior but not statistically superior to
sorafenib for overall survival (OS) (HR 0.92;
95% CI: 0.79, 1.06).
• Median OS in the lenvatinib arm was 13.6
months and 12.3 months in the sorafenib
arm.
• REFLECT also demonstrated a statistically
significant improvement in progression-free
survival (PFS) with lenvatinib as compared to
sorafenib.
• Median PFS was 7.3 months in the lenvatinib arm and 3.6
months in the sorafenib arm (HR 0.64; 95% CI: 0.55, 0.75;
p<0.001) per modified RECIST for HCC (mRECIST)
24. FDA Approval
• On August 16, 2018, lenvatinib (Lenvima) was approved for the first-
line treatment of patients with unresectable hepatocellular
carcinoma
• The recommended lenvatinib dosages for patients with HCC :
• 12 mg orally once daily in patients 60 kg or greater actual body weight or
• 8 mg orally once daily in patients less than 60 kg actual body weight.
ESMO 2018
25. Efek Samping
Hematologi (Jumlah %) Non Hematologi (Jumlah %)
Kenaikan bilirubin darah (15%) Hand and foot syndrome (27%)
Diare (39%)
Hipertensi (42%)
Penurunan nafsu makan (34%)
Penurunan berat badan (31%)
Lemas (30%)
Kerontokan rambut (3%)
Proteinuria (25%)
Gangguan suara (24%)
Mual (20%)
Nyeri abdomen (17%)
Peningkatan transaminase (14%)
Hipotiroid (14%)
Muntah (16%)
Konstipasi (16%)
Bercak merah (10%)
27. Osimertinib (Tagrisso)
•Osimertinib is a third generation, irreversible, oral EGFR-
TKI that inhibits both EGFR mutations and EGFR T790M
resistance mutations
•Osimertinib is a tyrosine kinase inhibitor, which acts by
blocking the activity of the epidermal growth factor
receptor (EGFR).
28. FDA Approval
• 2016: Osimertinib 2L for EGFR-TKI resistant disease for patients with
T790M mutation
• 2017: granted approval for 1st-line treatment of patients with
metastatic NSCLC whose tumours have EGFR mutations (exon 19
deletions or exon 21 L858R mutations); In 2018 osimertinib got full
approval
• 2018: Osimertinib as monotherapy for the 1st-line treatment of adult
patients with locally-advanced or metastatic NSCLC with activating
EGFR mutations
29. FLAURA Study
• FLAURA enrolled treatment naive patients aged ≥18 years (≥20 in
Japan) with Ex19del/L858R EGFR-mutated advanced NSCLC, and WHO
performance status 0–1; patients having stable CNS metastases that
did not require steroids for ≥2 weeks were allowed.
• 279 patients were treated with oral osimertinib at 80 mg once daily
and 277 patients received either gefitinib at 250 mg daily or erlotinib
150 mg orally per day.
30. FLAURA Study
• Survival data : the median overall survival with osimertinib
was 38.6 months versus 31.8 months with first generation
EGFR-TKIs, with a hazard ratio of 0.799 (p=0.0462).
• More than half (54%) of patients in the osimertinib group
were alive at three years compared to 44% in the standard
care group
a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4).
Lenvatinib inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET.
also exhibits antiproliferative activity in hepatocellular carcinoma cell lines dependent on activated FGFR signaling with a concurrent inhibition of FGF-receptor substrate 2α phosphorylation.
