Kleinzelliges Lungenkarzinom

Das kleinzellige Lungenkarzinom stellt eine besonders aggressive Tumorentität dar und ist durch schnellen Progress, sehr frühe Metastasierung und eine schlechte Prognose charakterisiert. Nur wenige Patienten werden in einem frühen Erkrankungsstadium diagnostiziert. Die systemische Therapie stellt die entscheidende Therapieform für die Mehrzahl der Patienten dar. Kürzlich konnte das systemische Therapiespektrum durch die Implementierung der Immuntherapie erstmal seit Jahrzehnten erweitert werden.

Abstract

Small cell lung cancer is an aggressive cancer entity and characterized by rapid progression, early distant metastasis and poor prognosis. Only the minority of patients presents with a non-metastatic stage disease where chemo-radiotherapy or – in very selected cases – even surgical resection may be discussed. For most patients, the efficacy of systemic therapy is crucial. However, although most patients respond to platinum doublet chemotherapy, virtually all patients with metastatic disease eventually develop tumor progression for which there are limited treatment options. Recently and for the first time since decades, the systemic approaches have been enriched by the implementation of immunotherapy. Moreover, novel therapeutic approaches such as new cytotoxic agents or further immune modulatory strategies are being tested in clinical studies that might broaden our treatment options in the future even further.

Kernaussagen

• Das kleinzellige Lungenkarzinom ist durch eine äußerst aggressive Verlaufsform, eine frühe Metastasierung und schlechte Prognose charakterisiert.

• Alle Patienten sollten nach der aktuellen TNM-Stadieneinteilung klassifiziert und im Tumorboard interdisziplinär besprochen werden.

• Bei kurativer Zielsetzung ist die Standardtherapie eine kombinierte Radiochemotherapie, die idealerweise simultan durchgeführt werden sollte.

• Im frühen Tumorstadium (N0, N1) kann eine vollständige Resektion mit adjuvanter Chemotherapie abgestrebt werden.

• Die Mehrzahl der Tumoren werden bereits im metastasierten Stadium diagnostiziert, bei denen eine (Kombinations-)Chemotherapie mit palliativer Intention die Standardtherapie darstellt.

• Als neuer Therapiestandard im fortgeschrittenen Stadium gilt die Kombination aus Platin, Etoposid und den Checkpointinhibitoren Atezolizumab oder Durvalumab.

Schlüsselwörter

Lungenkrebs - Bronchialkarzinom - Chemotherapie - Strahlentherapie - Tumorresektion - Checkpointinhibitor

Keywords

pulmonary cancer - bronchial carcinoma - chemotherapy - radiation therapy - tumor resection - checkpoint inhibitor

Publication History

Article published online:
19 April 2021

• Literatur

• 1 Robert Koch-Institut. Bericht zum Krebsgeschehen in Deutschland 2016. Im Internet (Stand 19.02.2021): https://www.krebsdaten.de/Krebs/DE/Content/Publikationen/Krebsgeschehen/Krebsgeschehen_node.html
• 2 Nicholson AG, Chansky K, Crowley J. et al. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the Revision of the Clinical and Pathologic Staging of Small Cell Lung Cancer in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2016; 11: 300-311
• 3 Goeckenjan G, Sitter H, Thomas M. et al. Prevention, diagnosis, therapy, and follow-up of lung cancer: interdisciplinary guideline of the German Respiratory Society and the German Cancer Society. Pneumologie 2010; 65: 39-59
• 4 Wolf M, Eberhardt W, Martin Früh M. et al. Lungenkarzinom, kleinzellig (SCLC). Onkopedia Leitlinie 2017. Im Internet (Stand 19.02.2021): https://www.onkopedia.com/de/onkopedia/guidelines/lungenkarzinom-kleinzellig-sclc/@@guideline/html/index.html
• 5 Schreiber D, Rineer J, Weedon J. et al. Survival outcomes with the use of surgery in limited-stage small cell lung cancer: should its role be re-evaluated?. Cancer 2010; 116: 1350-1357
• 6 Wong AT, Rineer J, Schwartz D. et al. Assessing the impact of postoperative radiation therapy for completely resected limited-stage small cell lung cancer using the National Cancer Database. J Thorac Oncol 2016; 11: 242-248
• 7 Auperin A, Arriagada R, Pignon JP. et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999; 341: 476-484
• 8 Pezzi TA, Fang P, Gjyshi O. et al. Rates of overall survival and intracranial control in the magnetic resonance imaging era for patients with limited-stage small cell lung cancer with and without prophylactic cranial irradiation. JAMA Netw Open 2020; 3: e201929
• 9 Brown PD, Ahluwalia MS, Khan OH. et al. Whole-Brain Radiotherapy for Brain Metastases: Evolution or Revolution?. J Clin Oncol 2018; 36: 483-491
• 10 Souhami RL, Law K. Longevity in small cell lung cancer. A report to the Lung Cancer Subcommittee of the United Kingdom Coordinating Committee for Cancer Research. Br J Cancer 1990; 61: 584-589
• 11 Horn L, Mansfield AS, Szczesna A. et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med 2018; 379: 2220-2229
• 12 Paz-Ares L, Dvorkin M, Chen Y. et al. 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 2019; 394: 1929-1939
• 13 O'Brien ME, Ciuleanu TE, Tsekov H. et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol 2006; 24: 5441-5447
• 14 von Pawel J, Jotte R, Spigel DR. et al. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol 2014; 32: 4012-4019
• 15 Inomata M, Hayashi R, Tokui K. et al. Outcome and prognostic factors in patients with small cell lung cancer who receive third-line chemotherapy. Tumori 2014; 100: 507-511
• 16 Slotman B, Faivre-Finn C, Kramer G. et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007; 357: 664-672
• 17 Takahashi T, Yamanaka T, Seto T. et al. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 2017; 18: 663-671
• 18 Slotman BJ, van Tinteren H, Praag JO. et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet 2014; 385: 36-42
• 19 Yu H, Batenchuk C, Badzio A. et al. PD-L1 Expression by Two Complementary Diagnostic Assays and mRNA In Situ Hybridization in Small Cell Lung Cancer. J Thorac Oncol 2016; 12: 110-120
• 20 Reck M, Luft A, Szczesna A. et al. Phase III Randomized Trial of Ipilimumab Plus Etoposide and Platinum Versus Placebo Plus Etoposide and Platinum in Extensive-Stage Small-Cell Lung Cancer. J Clin Oncol 2016;
• 21 Pujol J-L, Greillier L, Audigier-Valette C. et al. A Randomized Non-Comparative Phase II Study of Anti-Programmed Cell Death-Ligand 1 Atezolizumab or Chemotherapy as Second-Line Therapy in Patients With Small Cell Lung Cancer: Results From the IFCT-1603 Trial. J Thorac Oncol 2019; 14: 903-913
• 22 Ott PA, Elez E, Hiret S. et al. Pembrolizumab in patients with extensive-stage small-cell lung cancer: results from the phase Ib KEYNOTE-028 Study. J Clin Oncol 2017;
• 23 Ready NE, Ott PA, Hellmann MD. et al. Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort. J Thorac Oncol 2020; 15: 426-435
• 24 Owonikoko TK, Kim HR, Govindan R. et al. Nivolumab (nivo) plus ipilimumab (ipi), nivo, or placebo (pbo) as maintenance therapy in patients (pts) with extensive disease small cell lung cancer (ED-SCLC) after first-line (1L) platinum-based chemotherapy (chemo): Results from the double-blind, randomized phase III CheckMate 451 study. Annals of Oncology 2019; LBA1_PR 30
• 25 Rudin CM, Awad MM, Navarro A. et al. KEYNOTE-604: Pembrolizumab (pembro) or placebo plus etoposide and platinum (EP) as first-line therapy for extensive-stage (ES) small-cell lung cancer (SCLC). J Clin Oncol 2020; 38: 9001
• 26 Leal T, Wang Y, Dowlati A. et al. Randomized phase II clinical trial of cisplatin/carboplatin and etoposide (CE) alone or in combination with nivolumab as frontline therapy for extensive-stage small cell lung cancer (ES-SCLC): ECOG-ACRIN EA5161. J Clin Oncol 2020; 38: 9000
• 27 Markham A. Lurbinectedin: first approval. Drugs 2020; 80: 1345-1353
• 28 Trigo J, Subbiah V, Besse B. et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol 2020; 21: 645-654