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    Recent Therapeutic Advances in ES-SCLC: Dr. Andika Chandra Putra, PH.D, SP.P (K)

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    dicky wahyudi
    The document discusses recent clinical trials and meta-analyses on immunotherapy treatments for extensive-stage small cell lung cancer (ES-SCLC). Several phase III trials showed that adding immune checkpoint inhibitors like atezolizumab, pembrolizumab and serplulimab to first-line chemotherapy improved overall survival and progression-free survival compared to chemotherapy alone. A network meta-analysis found serplulimab plus chemotherapy had the highest probability of better OS and PFS outcomes with no significant differences in objective response rates or grade 3 or higher adverse effects between different treatment options.

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    Recent Therapeutic Advances in ES-SCLC: Dr. Andika Chandra Putra, PH.D, SP.P (K)

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    dicky wahyudi
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    The document discusses recent clinical trials and meta-analyses on immunotherapy treatments for extensive-stage small cell lung cancer (ES-SCLC). Several phase III trials showed that adding immune checkpoint inhibitors like atezolizumab, pembrolizumab and serplulimab to first-line chemotherapy improved overall survival and progression-free survival compared to chemotherapy alone. A network meta-analysis found serplulimab plus chemotherapy had the highest probability of better OS and PFS outcomes with no significant differences in objective response rates or grade 3 or higher adverse effects between different treatment options.

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    The document discusses recent clinical trials and meta-analyses on immunotherapy treatments for extensive-stage small cell lung cancer (ES-SCLC). Several phase III trials showed that adding immune checkpoint inhibitors like atezolizumab, pembrolizumab and serplulimab to first-line chemotherapy improved overall survival and progression-free survival compared to chemotherapy alone. A network meta-analysis found serplulimab plus chemotherapy had the highest probability of better OS and PFS outcomes with no significant differences in objective response rates or grade 3 or higher adverse effects between different treatment options.

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    25 views19 pages

    Recent Therapeutic Advances in ES-SCLC: Dr. Andika Chandra Putra, PH.D, SP.P (K)

    Uploaded by

    dicky wahyudi
    The document discusses recent clinical trials and meta-analyses on immunotherapy treatments for extensive-stage small cell lung cancer (ES-SCLC). Several phase III trials showed that adding immune checkpoint inhibitors like atezolizumab, pembrolizumab and serplulimab to first-line chemotherapy improved overall survival and progression-free survival compared to chemotherapy alone. A network meta-analysis found serplulimab plus chemotherapy had the highest probability of better OS and PFS outcomes with no significant differences in objective response rates or grade 3 or higher adverse effects between different treatment options.

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    Recent Therapeutic Advances in ES-SCLC

    Dr. Andika Chandra Putra, Ph.D, Sp.P(K)


    Small-cell lung cancer
    SCLC: Staging and General Approach to Treatment
    Published SCLC immunotherapy studies, focusing on ES-SCLC

    ES-SCLC

    First-line maintenance 2/3 line of treatment


    First-line treatment
    therapy

    IMpower133 Keynote-604 CAPSTONE-1 CheckMate-451 CheckMate-331


    (Atezolizumab) (Pembrolizumab) (Adebrelimab) (Nivolumab) (Nivolumab)
    Phase III
    Clinical CASPIAN TQB2450
    RATIONALE 312
    studies (Durvalumab) +ANIO+EP
    ASTRUM-005 JS001+EP
    (Serplulimab) ZKAB001+EP

    BGB-A317-206 NCT02359019 PASSION


    (Tislelizumab) (Camrelizumab)

    Phase I/II EA5161 CheckMate-032


    (Nivolumab)
    Clinical
    studies Keynote-028/158
    (Pembrolizumab)

    IFCT-1603

    The phase I/II study In progress/not The study reached The study did not reach
    reported endpoints reported the primary to the end
    endpoint
    Phase III Trials: Addition of Anti‒PD-L1 Checkpoint Inhibitors to First-
    line Platinum + Etoposide in ES-SCLC

    IMpower1331,2 CASPIAN3
    Stratified by sex, ECOG PS 0 vs 1, brain metastases (yes vs no) Stratified by planned carboplatin vs cisplatin
    Induction Maintenance
    Induction: 4 x 21-day cycles Maintenance* D + T + EP†
    D + T Q4W
    Patients with Q3W x 4 cycles
    Patients with until PD
    Atezolizumab + treatment-naive (n = 268)
    measurable ES-SCLC; Atezo
    Carboplatin/Etoposide ES-SCLC;
    ECOG PS 0/1; no prior until PD
    (n = 201) WHO PS 0/1; D + EP†
    systemic therapy for D Q4W
    asymptomatic or Q3W x 4 cycles
    ES-SCLC; treated, until PD
    treated and stable (n = 268)
    asymptomatic brain Placebo +
    Placebo brain metastases
    metastases eligible Carboplatin/Etoposide
    until PD (N = 805) EP†
    (N = 403) (n = 202) Optional
    Q3W x 4-6 cycles
    PCI
    *PCI per local SoC. (n = 269)
    †Either carboplatin or cisplatin.
    ▪ Coprimary endpoints: OS, PFS by investigator ▪ Primary endpoint: OS
    ▪ Secondary endpoints: ORR, DoR, safety ▪ Secondary endpoints: PFS, ORR, safety/tolerability, PROs

    1. Liu. JCO. 2021;39:619. 2. Horn. NEJM. 2018;379:2220. 3. Paz-Ares. ESMO Open. 2022;7:100408.
    Phase III Trials: First-line Platinum/Etoposide + ICI in ES-SCLC
    Effect of first-line serplulimab vs placebo added to chemotherapy on
    survival in patients with extensive-stage small cell lung cancer. The
    ASTRUM-005 randomized clinical trial
    Cheng Y, Han L, et al. JAMA 2022;328(12):1223-32

    Presented in ESMO Asia, Singapore 2022.


    Effect of first-line serplulimab vs placebo added to chemotherapy on survival in
    patients with extensive-stage small cell lung cancer. The ASTRUM-005
    randomized clinical trial
    Effect of first-line serplulimab vs placebo added to chemotherapy on
    survival in patients with extensive-stage small cell lung cancer. The
    ASTRUM-005 randomized clinical trial
    Updated OS in Subgroups
    Effect of first-line serplulimab vs placebo added to chemotherapy on
    survival in patients with extensive-stage small cell lung cancer. The
    ASTRUM-005 randomized clinical trial
    Effect of first-line serplulimab vs placebo added to chemotherapy on
    survival in patients with extensive-stage small cell lung cancer. The
    ASTRUM-005 randomized clinical trial
    Effect of first-line serplulimab vs placebo added to chemotherapy on
    survival in patients with extensive-stage small cell lung cancer. The
    ASTRUM-005 randomized clinical trial
    Effect of first-line serplulimab vs placebo added to chemotherapy on
    survival in patients with extensive-stage small cell lung cancer. The
    ASTRUM-005 randomized clinical trial
    Effect of first-line serplulimab vs placebo added to chemotherapy on
    survival in patients with extensive-stage small cell lung cancer. The
    ASTRUM-005 randomized clinical trial
    Efficacy and safety of first-line immunotherapy plus chemotherapy in
    treating patients with extensive-stage small cell lung cancer: A Bayesian
    network meta-analysis
    Zhang T, Li W, et al. Front Immunol. 2023;14:1197044
    • Metode: Meta-analisis (n= 4.352 pasien, 9 RCT).
    • Subjek: Pasien dengan SCLC stadium ekstensif.
    • Terapi: Lini pertama imunoterapi plus kemoterapi
    ✓ Ipilimumab plus etoposide/paclitaxel dan platinum
    ✓ Durvalumab plus tremelimumab plus platinum dan
    etoposide
    ✓ Pembrolizumab plus etoposide dan platinum
    ✓ Adebrelimab plus carboplatin dan etoposide
    ✓ Serplulimab plus carboplatin dan etoposide
    ✓ Atezolizumab plus tiragolumab plus carboplatin dan
    etoposide
    ✓ Nivolumab plus carboplatin dan etoposide
    Efficacy and safety of first-line immunotherapy plus chemotherapy in
    treating patients with extensive-stage small cell lung cancer: A Bayesian
    network meta-analysis
    Zhang T, Li W, et al. Front Immunol. 2023;14:1197044

    Kesimpulan:
    •Serplulimab plus kemoterapi memiliki probabilitas paling tinggi untuk OS dan PFS yang lebih baik.
    •Tidak terdapat perbedaan bermakna dalam hal ORR dan efek samping derajat ≥ 3 di antara berbagai
    pilihan terapi.
    Summary

    In the updated analysis, serplulimab plus chemotherapy continued to provide benefits in OS,
    PFS, ORR, and DOR compared with placebo plus chemotherapy.
    ➢ Median OS: 15.8 vs. 11.1 months; HR, 0.62; p<0.001.
    ➢ Median PFS by IRRC per RECIST v1.1: 5.8 vs. 4.3 months; HR, 0.47; p<0.001.
    ➢ ORR: 68.9% vs. 58.7%; median DOR: 6.5 vs. 4.2 months (HR, 0.45) as assessed by IRRC per
    RECIST v1.1.
    ➢ The improved OS with serplulimab plus chemotherapy was observed across subgroups,
    including Asian and non-Asian.
    The safety profile was similar between the two groups and consistent with that previously
    observed.
    TERIMA KASIH

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