nach oben

Cancer Immunology, Immunotherapy

Erschienen in:

27.09.2021 | Original Article

Efficacy and safety of atezolizumab, in combination with etoposide and carboplatin regimen, in the first-line treatment of extensive-stage small-cell lung cancer: a single-center experience

verfasst von: Seoyoung Lee, Hyo Sup Shim, Beung-Chul Ahn, Sun Min Lim, Hye Ryun Kim, Byoung Chul Cho, Min Hee Hong

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 5/2022

Einloggen, um Zugang zu erhalten

Abstract

Background

Patients with small-cell lung cancer (SCLC) have a dismal prognosis with limited overall survival (OS) despite a high response rate to chemotherapy. Recently, immune checkpoint inhibitors, combined with chemotherapy, as the first-line treatment for extensive-stage (ES)-SCLC have shown improvement in clinical outcomes.

Patients and methods

Real-world data from 68 Korean ES-SCLC patients, treated with atezolizumab, etoposide, and carboplatin at Yonsei Cancer Center between June 2019 and November 2020, were retrospectively analyzed to determine safety and efficacy using Cox regression analysis.

Results

The median follow-up was 11.6 months. The median progression-free survival was 4.6 months (95% confidence interval [CI] 4.0–5.2), and the median OS was 12.0 months (95% CI 7.4–16.6). Baseline bone metastasis, immune-related adverse events (IRAEs), and elevated LDH were related to OS (hazard ratio 2.18, 0.33, and 4.64; P = 0.05, 0.02, and 0.003, respectively). Among the 42 patients with disease progression, liver metastasis progression and baseline bone metastasis were associated with inferior OS, but without statistical significance (hazard ratio 2.47 and 1.97; P = 0.25 and 0.26, respectively). Overall, 61 (89.7%) patients experienced treatment-related adverse events (TRAEs), with hematologic toxicities as the most common grade 3–4 TRAEs. Twenty-two (32.4%) patients experienced IRAEs, with skin rash as the most common, and five (7.4%) patients had grade-3 IRAEs (pneumonitis, hyperglycemia, and aspartate aminotransferase elevation).

Conclusion

Atezolizumab, combined with etoposide and carboplatin, showed efficacy and safety in our real-world data. Further studies are needed to predict the response to immunotherapy in SCLC.

Nur mit Berechtigung zugänglich

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492CrossRefPubMed

Barta JA, Powell CA, Wisnivesky JP (2019) Global epidemiology of lung cancer. Ann Glob Health. https://doi.org/10.5334/aogh.2419CrossRefPubMedPubMedCentral

Farago AF, Keane FK (2018) Current standards for clinical management of small cell lung cancer. Transl Lung Cancer Res 7(1):69–79. https://doi.org/10.21037/tlcr.2018.01.16CrossRefPubMedPubMedCentral

Schabath MB, Nguyen A, Wilson P, Sommerer KR, Thompson ZJ, Chiappori AA (2014) Temporal trends from 1986 to 2008 in overall survival of small cell lung cancer patients. Lung Cancer 86(1):14–21. https://doi.org/10.1016/j.lungcan.2014.07.014CrossRefPubMed

Ready N, Farago AF, de Braud F, Atmaca A, Hellmann MD, Schneider JG et al (2019) Third-line nivolumab monotherapy in recurrent SCLC: checkmate 032. J Thorac Oncol 14(2):237–244. https://doi.org/10.1016/j.jtho.2018.10.003CrossRefPubMed

Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM (2017) Pembrolizumab in patients with extensive-stage small-cell lung cancer: results from the phase Ib KEYNOTE-028 study. J Clin Oncol 35(34):3823–3829. https://doi.org/10.1200/jco.2017.72.5069CrossRefPubMed

Chung HC, Piha-Paul SA, Lopez-Martin J, Schellens JHM, Kao S, Miller WH Jr et al (2020) Pembrolizumab after two or more lines of previous therapy in patients with recurrent or metastatic SCLC: results from the KEYNOTE-028 and KEYNOTE-158 studies. J Thorac Oncol 15(4):618–627. https://doi.org/10.1016/j.jtho.2019.12.109CrossRefPubMed

Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ et al (2018) First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med 379(23):2220–2229. https://doi.org/10.1056/NEJMoa1809064CrossRefPubMed

Mansfield AS, Każarnowicz A, Karaseva N, Sánchez A, De Boer R, Andric Z et al (2020) Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Ann Oncol 31(2):310–317. https://doi.org/10.1016/j.annonc.2019.10.021CrossRefPubMed

10.

Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D et al (2019) Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet 394(10212):1929–1939. https://doi.org/10.1016/s0140-6736(19)32222-6CrossRefPubMed

11.

Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D et al (2020) Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. https://doi.org/10.1016/s1470-2045(20)30539-8CrossRefPubMed

12.

Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T et al (2020) Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: randomized, double-blind, phase III KEYNOTE-604 study. J Clin Oncol 38(21):2369–2379. https://doi.org/10.1200/jco.20.00793CrossRefPubMedPubMedCentral

13.

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. https://doi.org/10.1016/j.ejca.2008.10.026CrossRefPubMed

14.

Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (2009) National Cancer Institute. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. Accessed 28 May 2009

15.

Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F et al (2018) Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 378(22):2078–2092. https://doi.org/10.1056/NEJMoa1801005CrossRefPubMed

16.

Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J et al (2018) Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med 379(21):2040–2051. https://doi.org/10.1056/NEJMoa1810865CrossRefPubMed

17.

Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G, Jr. et al (2019) Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet 394(10212):1915–1928. https://doi.org/10.1016/s0140-6736(19)32591-7CrossRefPubMed

18.

Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H et al (2018) Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 379(22):2108–2121. https://doi.org/10.1056/NEJMoa1809615CrossRefPubMed

19.

Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D et al (2019) Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 380(12):1116–1127. https://doi.org/10.1056/NEJMoa1816714CrossRefPubMed

20.

Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY et al (2020) Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 382(20):1894–1905. https://doi.org/10.1056/NEJMoa1915745CrossRefPubMed

21.

Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B et al (2021) Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 384(9):829–841. https://doi.org/10.1056/NEJMoa2026982CrossRefPubMedPubMedCentral

22.

Hamilton G, Rath B (2019) Immunotherapy for small cell lung cancer: mechanisms of resistance. Expert Opin Biol Ther 19(5):423–432. https://doi.org/10.1080/14712598.2019.1592155CrossRefPubMed

23.

Galluzzi L, Humeau J, Buqué A, Zitvogel L, Kroemer G (2020) Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat Rev Clin Oncol 17(12):725–741. https://doi.org/10.1038/s41571-020-0413-zCrossRefPubMed

24.

Golden EB, Frances D, Pellicciotta I, Demaria S, Helen Barcellos-Hoff M, Formenti SC (2014) Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death. Oncoimmunology 3:e28518. https://doi.org/10.4161/onci.28518CrossRefPubMedPubMedCentral

25.

Nakazawa K, Kurishima K, Tamura T, Kagohashi K, Ishikawa H, Satoh H, Hizawa N (2012) Specific organ metastases and survival in small cell lung cancer. Oncol Lett 4(4):617–620. https://doi.org/10.3892/ol.2012.792CrossRefPubMedPubMedCentral

26.

Landi L, D’Incà F, Gelibter A, Chiari R, Grossi F, Delmonte A et al (2019) Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer. J Immunother Cancer 7(1):316. https://doi.org/10.1186/s40425-019-0793-8CrossRefPubMedPubMedCentral

27.

Ricciuti B, Genova C, De Giglio A, Bassanelli M, Dal Bello MG, Metro G, Brambilla M, Baglivo S, Grossi F, Chiari R (2019) Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis. J Cancer Res Clin Oncol 145(2):479–485. https://doi.org/10.1007/s00432-018-2805-3CrossRefPubMed

28.

Grangeon M, Tomasini P, Chaleat S, Jeanson A, Souquet-Bressand M, Khobta N et al (2019) Association between immune-related adverse events and efficacy of immune checkpoint inhibitors in non-small-cell lung cancer. Clin Lung Cancer 20(3):201–207. https://doi.org/10.1016/j.cllc.2018.10.002CrossRefPubMed

29.

Sato K, Akamatsu H, Murakami E, Sasaki S, Kanai K, Hayata A et al (2018) Correlation between immune-related adverse events and efficacy in non-small cell lung cancer treated with nivolumab. Lung Cancer 115:71–74. https://doi.org/10.1016/j.lungcan.2017.11.019CrossRefPubMed

30.

Haratani K, Hayashi H, Chiba Y, Kudo K, Yonesaka K, Kato R et al (2018) Association of immune-related adverse events with nivolumab efficacy in non-small-cell lung cancer. JAMA Oncol 4(3):374–378. https://doi.org/10.1001/jamaoncol.2017.2925CrossRefPubMed

31.

Zhang Z, Li Y, Yan X, Song Q, Wang G, Hu Y, Jiao S, Wang J (2019) Pretreatment lactate dehydrogenase may predict outcome of advanced non small-cell lung cancer patients treated with immune checkpoint inhibitors: a meta-analysis. Cancer Med 8(4):1467–1473. https://doi.org/10.1002/cam4.2024CrossRefPubMedPubMedCentral

32.

Zhang X, Guo M, Fan J, Lv Z, Huang Q, Han J, Wu F, Hu G, Xu J, Jin Y (2016) Prognostic significance of serum LDH in small cell lung cancer: A systematic review with meta-analysis. Cancer Biomark 16(3):415–423. https://doi.org/10.3233/cbm-160580CrossRefPubMed

33.

Schultheis AM, Scheel AH, Ozretić L, George J, Thomas RK, Hagemann T, Zander T, Wolf J, Buettner R (2015) PD-L1 expression in small cell neuroendocrine carcinomas. Eur J Cancer 51(3):421–426. https://doi.org/10.1016/j.ejca.2014.12.006CrossRefPubMed

34.

Antonia SJ, López-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP et al (2016) Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol 17(7):883–895. https://doi.org/10.1016/s1470-2045(16)30098-5CrossRefPubMed

35.

Rudin CM, Poirier JT, Byers LA, Dive C, Dowlati A, George J et al (2019) Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data. Nat Rev Cancer 19(5):289–297. https://doi.org/10.1038/s41568-019-0133-9CrossRefPubMedPubMedCentral

36.

Gay CM, Stewart CA, Park EM, Diao L, Groves SM, Heeke S et al (2021) Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. Cancer Cell 39(3):346-360.e347. https://doi.org/10.1016/j.ccell.2020.12.014CrossRefPubMedPubMedCentral

37.

Yu J, Green MD, Li S, Sun Y, Journey SN, Choi JE et al (2021) Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination. Nat Med 27(1):152–164. https://doi.org/10.1038/s41591-020-1131-xCrossRefPubMedPubMedCentral

Titel: Efficacy and safety of atezolizumab, in combination with etoposide and carboplatin regimen, in the first-line treatment of extensive-stage small-cell lung cancer: a single-center experience
verfasst von: Seoyoung Lee
Hyo Sup Shim
Beung-Chul Ahn
Sun Min Lim
Hye Ryun Kim
Byoung Chul Cho
Min Hee Hong
Publikationsdatum: 27.09.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 5/2022
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-021-03052-w

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Efficacy and safety of atezolizumab, in combination with etoposide and carboplatin regimen, in the first-line treatment of extensive-stage small-cell lung cancer: a single-center experience