30- und 90-Tage-Letalität bei Patienten mit Lungenkarzinom im Stadium IV in Abhängigkeit der Primärtherapie

Zusammenfassung

Die frühe Letalität nach der Therapieeinleitung bei Patienten mit Lungenkarzinom im Stadium IV stand bisher selten im Fokus wissenschaftlicher Arbeiten. Die wenige verbleibende Zeit zwischen Diagnosestellung, Therapiebeginn und Todeseintritt sowie die evtl. beeinflussenden Faktoren beschäftigen jedoch Patienten und Behandler in hohem Maße. Entsprechend ist das Ziel dieser Arbeit die 30- und 90-Tage-Letalität nach Einleitung einer First-Line-Therapie zu analysieren und mögliche Einflussfaktoren auf eine frühe Letalität zu eruieren. Hierzu wurden retrospektiv die Daten von 225 Patienten mit Lungenkarzinom im Stadium IV und Behandlung im Lungenkrebszentrum Martha-Maria Halle-Dölau und in der Lungenklinik Ballenstedt im Zeitraum vom 01. 01. 2017 bis zum 18. 05. 2020 erfasst. Therapieformen und Patientenmerkmale wurden mittels Häufigkeitsverteilung analysiert und die Überlebenswahrscheinlichkeiten durch die Kaplan-Meier-Methode geschätzt. Die Analyse der frühen Letalität aller tumorspezifisch behandelten Patienten brachte zum Zeitpunkt 30 Tage nach Therapiebeginn eine Letalität von 8,5 % und nach 90 Tagen eine Rate von 23,5 %. Im direkten Vergleich der unterschiedlichen Therapiegruppen fielen die Patienten mit einer Monotherapie mit Checkpointinhibitoren mit einer höheren Letalität auf (16,6 % nach 30 Tagen und 44,3 % nach 90 Tagen). Hingegen blieb die Letalität der Patienten der anderen Therapiegruppen bei unter 10 % nach 30 Tagen und unter 23,3 % nach 90 Tagen. Als Prädiktoren für eine höhere frühe Letalität konnten ein schlechter Allgemeinzustand, eine fortgeschrittene Tumorerkrankung, eine Polymetastasierung sowie die positive Raucheranamnese eruiert werden. Dagegen bestand kein relevanter Unterschied der Letalität zwischen den unterschiedlichen Tumorentitäten, dem Geschlecht sowie dem PD-L1- und Mutationsstatus. Mit dieser Analyse konnte eine sehr hohe, mit anderen Untersuchungen vergleichbare frühe Letalität bei Patienten mit Lungenkarzinom nachgewiesen werden. Relevante Unterschiede zwischen den Therapieformen verdeutlichen die Wichtigkeit einer individuellen Patientenselektion zu den jeweiligen Therapieoptionen und die rasche Entscheidung zu einer Therapieeinleitung.

Abstract

Early lethality after initiation of therapy in patients with stage IV lung cancer has rarely been the focus of scientific studies yet. The little time remaining between diagnosis, start of therapy and onset of death, as well as any influencing factors, are of special interest for both, patients and physician. Accordingly, the aim of this work was to analyze the 30- and 90-day morbidity after initiation of systemic therapy and to determine possible factors influencing early lethality. For this purpose, the data of 225 patients with stage IV lung cancer and treatment at the Martha-Maria Halle-Dölau Lung Cancer Center between 01/01/2017 and 05/18/2020 were retrospectively analyzed. Forms of therapy and patient characteristics were analyzed with a frequency distribution and the probability of survival was estimated using the Kaplan-Meier method. The analysis of the early morbidity of all tumor-specifically treated patients showed a morbidity of 8.5 % at day 30 after the start of therapy and a rate of 23.5 % after 90 days. In a direct comparison of the different therapy groups, the patients receiving mono-checkpointinhibition had higher lethality (16.6 % after 30 days and 44.3 % after 90 days). In contrast, the morbidity of patients in the other therapy groups remained below 10 % after 30 days and below 23.3 % after 90 days. A poor general condition, an advanced tumor disease, polymetastasis and a positive history of smoking could be determined as predictors for higher early lethality. In contrast, there was no relevant difference in morbidity between the different tumor entities, gender, PD-L1 and mutation status. With this analysis, very high early lethality, comparable to other studies, could be detected in patients with lung cancer. Relevant differences between the forms of therapy illustrate the importance of individual patient selection for the respective therapy options and the rapid decision to initiate therapy.

Publication History

Article published online:
23 July 2021

• Literatur

• 1 Khoja L, McGurk A, OʼHara C. et al. Mortality within 30 days following systemic anti-cancer therapy, a review of all cases over a 4 year period in a tertiary cancer centre. Eur J Cancer 2015; 51: 233-240
• 2 Ohe Y, Yamamoto S, Suzuki K. et al. Risk factors of treatment-related death in chemotherapy and thoracic radiotherapy for lung cancer. European Journal of Cancer 2001; 37: 54-63
• 3 Ang E, Newton LV. Thirty-day mortality after systemic anticancer treatment as a real-world, quality-of-care indicator: the Northland experience. Intern Med J 2018; 48: 403-408
• 4 Wallington M, Saxon EB, Bomb M. et al. 30-day mortality after systemic anticancer treatment for breast and lung cancer in England: a population-based, observational study. The Lancet Oncology 2016; 17: 1203-1216
• 5 Gibson AJW, Li H, D'Silva A. et al. Factors associated with early mortality in non-small cell lung cancer patients following systemic anti-cancer therapy: A 10 year population-based study. Lung Cancer 2019; 134: 141-146
• 6 Horn L, Mansfield AS, Szczęsna A. et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med 2018; 379: 2220-2229
• 7 Gandhi L, Rodríguez-Abreu D, Gadgeel S. et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med 2018; 378: 2078-2092
• 8 Peters S, Camidge DR, Shaw AT. et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med 2017; 377: 829-838
• 9 Reck M, Rodríguez-Abreu D, Robinson AG. et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med 2016; 375: 1823-1833
• 10 Minami-Shimmyo Y, Ohe Y, Yamamoto S. et al. Risk factors for treatment-related death associated with chemotherapy and thoracic radiotherapy for lung cancer. J Thorac Oncol 2012; 7: 177-182
• 11 Spencer K, Morris E, Dugdale E. et al. 30 day mortality in adult palliative radiotherapy – A retrospective population based study of 14,972 treatment episodes. Radiother Oncol 2015; 115: 264-271
• 12 Mok TSK, Wu Y-L, Kudaba I. et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet 2019; 393: 1819-1830
• 13 Solomon BJ, Mok T, Kim D-W. et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014; 371: 2167-2177
• 14 Zhou C, Wu YL, Chen G. et al. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol 2015; 26: 1877-1883
• 15 Yang JC-H, Wu Y-L, Schuler M. et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. The Lancet Oncology 2015; 16: 141-151
• 16 Socinski MA, Jotte RM, Cappuzzo F. et al. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med 2018; 378: 2288-2301
• 17 Temel JS, McCannon J, Greer JA. et al. Aggressiveness of care in a prospective cohort of patients with advanced NSCLC. Cancer 2008; 113: 826-833
• 18 Kas B, Talbot H, Ferrara R. et al. Clarification of Definitions of Hyperprogressive Disease During Immunotherapy for Non-Small Cell Lung Cancer. JAMA Oncol 2020;
• 19 Kim CG, Kim KH, Pyo K-H. et al. Hyperprogressive disease during PD-1/PD-L1 blockade in patients with non-small-cell lung cancer. Ann Oncol 2019; 30: 1104-1113
• 20 Morita M, Tamiya M, Fujimoto D. et al. Prediction of patients with a tumor proportion score 50 % who do not respond to first-line monotherapy with pembrolizumab. BMC Cancer 2020; 20: 93
• 21 Mok TS, Wu Y-L, Thongprasert S. et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947-957
• 22 Callahan MK, Rampal R, Harding JJ. et al. Progression of RAS-mutant leukemia during RAF inhibitor treatment. N Engl J Med 2012; 367: 2316-2321
• 23 Mellema WW, Burgers SA, Smit EF. Tumor flare after start of RAF inhibition in KRAS mutated NSCLC: a case report. Lung Cancer 2015; 87: 201-203
• 24 Su F, Viros A, Milagre C. et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med 2012; 366: 207-215
• 25 Sweeney CJ, Zhu J, Sandler AB. et al. Outcome of patients with a performance status of 2 in Eastern Cooperative Oncology Group Study E1594. Cancer 2001; 92: 2639-2647
• 26 Langer C, Li S, Schiller JH. et al. Randomized phase II trial of paclitaxel plus carboplatin or gemcitabine plus cisplatin in Eastern Cooperative Oncology Group performance status 2 non-small-cell lung cancer patients: ECOG 1599. J Clin Oncol 2007; 25: 418-423
• 27 Schiller JH, Harrington D, Belani CP. et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346: 92-98
• 28 Lee SM, Khan I, Upadhyay S. et al. First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology 2012; 13: 1161-1170
• 29 Thatcher N, Chang A, Parikh P. et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). The Lancet 2005; 366: 1527-1537
• 30 Zamboni MM, da Silva CT, Baretta R. et al. Important prognostic factors for survival in patients with malignant pleural effusion. BMC Pulm Med 2015; 15: 29
• 31 Parsons A, Daley A, Begh R. et al. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ 2010; 340: b5569
• 32 Tsao AS, Liu D, Lee JJ. et al. Smoking affects treatment outcome in patients with advanced nonsmall cell lung cancer. Cancer 2006; 106: 2428-2436
• 33 Tammemagi CM, Neslund-Dudas C, Simoff M. et al. In lung cancer patients, age, race-ethnicity, gender and smoking predict adverse comorbidity, which in turn predicts treatment and survival. J Clin Epidemiol 2004; 57: 597-609
• 34 Thu KL, Vucic EA, Chari R. et al. Lung adenocarcinoma of never smokers and smokers harbor differential regions of genetic alteration and exhibit different levels of genomic instability. PLoS ONE 2012; 7: e33003
• 35 Dias M, Linhas R, Campainha S. et al. Lung cancer in never-smokers – what are the differences?. Acta Oncol 2017; 56: 931-935
• 36 Wolf M, Holle R, Hans K. et al. Analysis of prognostic factors in 766 patients with small cell lung cancer (SCLC): the role of sex as a predictor for survival. Br J Cancer 1991; 63: 986-992