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DEPARTEMEN KEDOKTERAN DALAM

UNIVERSITAS HASANUDDIN

Beban dunia nyata daridiinduksi kemoterapimyelosupresi pada

pasien dengan kecilparu-paru selkanker: analisis retrospektif
darimedis elektronikdata dari kanker komunitaspenyedia perawatan

Oleh: Estiani Ningsih

Pembimbing: dr. dimasBayu,Sp.PD, K-HOM

 PENGANTAR
• Kanker paru-paru sel kecil (SCLC) 13% dari semua kasus kanker paru-paru di Amerika Serikatkebanyakan
pasien didiagnosis pada stadium lanjut

• Prognosis buruk dengan tingkat kelangsungan hidup 5 tahun 6%, menurun menjadi 3% di antara pasien dengan
metastasis jauh

• Kemoterapitetap menjadi komponen utama pengobatan untuk tahap terbatas (LS-) dan tahap ekstensif (ES-)penyakit

• DiAmerika Serikat, agen kemoterapi sistemik cisplatindan carboplatin (agen platinum),etoposida,irinotecan,

paclitaxel, dantopotan

• Sampai saat ini, pengobatan standar lini pertama (1L) untuk SCLCdiAmerika Serikatetoposida
plusplatinumkarboplatin lebihcisplatinkarena kemanjurannya yang sebanding dan profil toksisitas yang
menguntungkan
 PENGANTAR

• Ini baru-baru ini disetujuiimunoterapidalam kombinasi dengan

platinum plusetoposidarejimen kemoterapi direkomendasikan
(kategori 1) untuk pengobatan sistemik 1L ES-SCLC
diPedoman NCCN
• Untuk20 tahun terakhir,topotan telah menjadi satu-satunya
rejimen pilihan untuk sistemik berikutnyaterapinamun,
pada bulan Juni 2020,lurbinectedindisetujui oleh FDA untuk
pengobatan sistemik lini kedua (2L) SCLC setelah kegagalan
terapi berbasis platinum
rejimenuntuk SCLCkerusakanke sel punca
hematopoietik dan sel progenitor di
tulangsumsum multilineage myelosupresi
 bermanifestasi sebagai kisaransitopenia
anemia,neutropenia,dantrombositopenia
 Metode
Data source Patient selection
and study design
• EMR data • Adult patients with SCLC
(jan 2016-Dec 2019) in
from the PSJH primary EMR
Providence St.
Joseph Health • Patients have received
• Providence chemotherapy in 1L or
both 1L and 2L-and-
Cancer beyond (2L+) treatment
Reporting Jan 2016-Dec 2018
Registry
• Myelosuppressive AEs,
• The dataset
treatment, and HCRU
40 oncology were assessed for the
clinics in the follow-up period of 12
United Stat months from the index
date, or until the date of
the last visit, date of
death, or the end of the
study period (December
2019)
Statistical Analyses
Study Measure
• Identified based on • Descriptive
laboratory values from EMR statistics were
data according to the used to describe
Common Toxicity Criteria patient
definition of grade 3 or above characteristics
AEs.
• Myelosuppressive AEs:
and outcomes
hemoglobin <8.0 g/dL;
absolute neutrophil count
<1,000 mm3 and platelet
count <50,000 mm³
• Treatment of
myelosuppressive
Aestransfusions (RBC or
platelet), G-CSF
administration, and ESA
useq
 Hasil
Sabarkarakteristik
A total of 347 patients
diagnosed with SCLC who had
received chemotherapy were
eligible for the analysis
The range age of patients was
65 (35–93) years, 48.7% were
female, and 88.8% were White.
Almost two-thirds of patients
(61.1%) presented with stage
IV (ES) disease at diagnosis.
Overall, 36.9%
current smokers, 26.5% as past
smokers; 6.1% were
reported as having never
smoked, and 30.5% as not asked
Hasil
 Hasil
Pola pengobatan
Among study patients (N=347) 1L
treatment, and 29.7% (n= 103) 
2L+ treatment
recorded EMR during the study
period
Yang palingumum2L+rejimen pengobatan
topotan(n=21 dari 103, 20,4%), terapi
kombinasi
denganipilimumabplusnivolumabataupembroli
zumab(n=20 dari 103,
19,4%),karboplatin(sendiri atau dalam
kombinasi denganirinotecanatauetoposida;
n=15 dari 103, 14,6%, dan paclitaxel (n=11
dari 103, 10,7%)
Over 70% of patients received
platinum plus etoposide
as 1L treatment (carboplatin plus
etoposide: n= 192, 55.3%;
cisplatin plus etoposide: n=67,
19.3%)
Overall, 7.5% (n= 26)immune
checkpoint inhibitor (atezolizumab
[n= 19], nivolumab [n= 4],
pembrolizumab [n= 2]durvalumab
[n= 1]) as part of their 1L treatment
regimen
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 Diskusi
Our findings 2/3 of patients experienced grade ≥ 3 myelosuppressive AEs, most commonly neutropenia and anemia,
during the study period similar between patients receiving 2L+ therapy and 1L

In clinical trials of treatments for ES-SCLC, the percentage of patients

1) Chemotherapy-induced Neutropenia observed in this
study 44.9 events per 100 patients across all lines of
therapy
with grade 3/4 neutropenia has ranged from 22.7% for atezolizumab
plus etoposide and carboplatin, and 24.5% , and 33.0% for etoposide
plus carboplatin, to higher rates of 44.0–86.5% for etoposide plus
cisplatin
An observational study by Igawa et al. reported a rate of
chemotherapy-induced neutropenia of 40.0% with etoposide plus
carboplatin in their patient population, which is broadly comparable with
the current study

2) Chemotherapy-induced anemia  41.1 events per 100 patients in this study

Several clinical trials of therapies for ES-SCLC (e.g. atezolizumab plus etoposide
and carboplatin, etoposide plus carboplatin, and etoposide plus cisplatin) have
reported rates of grade ≥ 3 anemia of <20%
 Diskusi

42.1% of patients in the current study had received radiation therapy since previous studies have shown that radiotherapy
is associated with bone marrow suppression and contributes to severe myelosuppression in patients with SCLC receiving
chemotherapy

Subgroup analysis indicated that patients who received radiation had higher rates of grade ≥ 3 myelosuppressive Aes
(particularly neutropenia and anemia) compared with those without radiation, suggesting that prior receipt of radiation
therapy may have contributed to some of the myelosuppressive Aes reported in this study
Diskusi

If untreated, ES-SCLC is usually fatal within 2–5 months

By comparison, median overall survival with 1L platinum plus etoposide is 8–10 months, and this further increases
to 12–13 months with the addition of an immune checkpoint inhibitor (atezolizumab or durvalumab).

Survival times with 2L topotecan treatment in patients with relapsed SCLC range from 6 to 8 months, with one
study reporting a survival improvement of 3 months with the addition of oral topotecan to best supportive care

In addition to prolonging survival, chemotherapy treatment may also provide symptom control, thereby improving quality
of lifethe clinical benefit of cytotoxic chemotherapy may outweigh the risk of toxicity for many patients with SCLC

The potential impact of myelosuppression on treatment outcomes must also be deliberated hematologic
AEs commonly lead to dose delays, dose reductions, and reductions in relative dose intensity
Diskusi

Di bulan Maret2021,trilaciclib, intravenabersepeda-bergantungkinase4/6 inhibitor, telah disetujui

oleh FDA AS untukkurangiinsiden yang diinduksi kemoterapimyelosupresi pada pasiendengan ES-
SCLC bila diberikan sebelum aplatinum/etoposida-atautopotan-mengandungrejimen

Sekarangmenyarankanrejimen untuk pengobatan primerES-SCLC

termasuk:penghambat pos pemeriksaan (atezolizumabataudurvalumab)
dikombinasi denganetoposidadan platinakemoterapi untuk 4 –6
perawatansiklus

Hampir2/3 pasien dengan SCLC memiliki penyakit stadium luas saat diagnosis, temuan penelitian
ini di SCLC harus memberikan wawasan penting kepada dokter mengenai pencegahan dan
penanganan.mielosupresifAE pada pasien dengan ES-SCLC
 Kesimpulan

In this real-world study, a large and meaningful proportion of patients with

SCLC experienced grade ≥ 3 hematologic toxicity, which was associated with a
substantial increase in HCRU

Multilineage myelosuppression places an ever greater real-world burden on

patients and the healthcare system in a community cancer care setting

Innovative or improved management strategies, which may include trilaciclib

and other novel agents for the treatment of one or more cytopenias, have the
potential to address this burde
Thank You