von Rajiv Shah ; Eva L. Buchmeier ; Hans-Georg Kopp ; Daniel C. Christoph ; Frank Griesinger ; Martin Reck ; Petra Hoffknecht ; Jonas Kuon ; Nikolaj Frost ; Christian Grohé ; Martin Faehling ; Jingting Luan ; Julia Roeper ; Paolo Chesi ; Miriam Blasi ; Martin Kimmich ; Till Olchers ; Helge Bischoff ; Laura Valentina Klotz ; Inn Chung ; Petros Christopoulos ; Michael Thomas
Background - Despite the approval of nivolumab/ipilimumab, the prognosis of patients with pleural mesothelioma (PM) remains poor. Although this combination has shown improved survival in the landmark CheckMate (CM)-743 trial, evidence from real-world settings remains limited. - Methods - In this retrospective, multicenter study, the outcome and safety data for 135 consecutive patients with first-line nivolumab/ipilimumab were evaluated among 1,575 adult patients with PM from 12 German cancer centers. Radiologic response and progression were analyzed according to the revised modified RECIST criteria. - Results - The median overall survival (OS) was 13.1 months for the unselected real-world cohort, and 15.5 months for CM-743-eligible patients (16.7 months for the non-epithelioid and 10 months for the epithelioid subtypes). Patients who experienced partial responses to nivolumab/ipilimumab had significantly longer survival than those without (24 months vs. 10.3 months; p = 0.00026). 37 % of patients experienced immune-related adverse events (irAEs), among whom 58 % had grade 3/4 toxicity. IrAEs of any grade were associated with longer survival (17.3 months vs. 11.7 months for patients without irAEs; p = 0.022). Furthermore, grade 1/2 irAEs were associated with even better outcomes when compared to grade 3/4 toxicities (22.7 months vs. 16.7 months median OS) and absence of toxicity (p < 0.0167 for trend). - Conclusions - Overall survival with first-line nivolumab/ipilimumab in the real-world setting is comparable to the CM-743 results among trial-eligible patients, especially with non-epithelioid tumors, but shorter for the unselected cohort. IrAEs, in particular those of low-grade, were associated with better outcomes. In the absence of predictive biomarkers and with few therapeutic options available, both dual checkpoint blockade and platinum-pemetrexed chemotherapy remain viable first-line regimens.
Lung cancer Amsterdam [u.a.] : Elsevier, 1985 207(2025) vom: Sept., Artikel-ID 108702, Seite 1-10 Online-Ressource
von Martin Metzenmacher ; Hans-Georg Kopp ; Frank Griesinger ; Niels Reinmuth ; Martin Sebastian ; Monika Serke ; Cornelius Florian Waller ; Michael Thomas ; Jochen Eggert ; Gerald Schmid-Bindert ; Mathias Hoiczyk ; Daniel Christian Christoph ; Martin Kimmich ; Burkhard Deuß ; Stephanie Seifert ; Swantje Held ; Martin Schuler ; Thomas Herold ; Frank Breitenbuecher ; Wilfried Ernst Erich Eberhardt
Background:Pemetrexed and cisplatin is a first-line standard in non-squamous non-small-cell lung cancer without targetable mutations. It became the backbone of checkpoint-inhibitor?chemotherapy combinations. Single high doses of cisplatin pose toxicity risks and require hyperhydration, potentially prolonging outpatient application. The aim of this study was to compare efficacy, safety and tolerability of split-dose cisplatin with the standard schedule.Methods:Patients with metastatic non-squamous non-small-cell lung cancer were randomly assigned to up to six 21-day cycles of pemetrexed 500?mg/m2 and cisplatin 75?mg/m2 on day 1 (arm A), or pemetrexed 500?mg/m2 (day 1) and cisplatin 40?mg/m2 (day 1?+?8, arm B), followed by pemetrexed maintenance. Primary endpoint was objective response rate. Secondary objectives were overall survival, progression-free survival, time to progression, treatment compliance, toxicity profile, and quality of life.Results:We enrolled 130 patients (129 evaluable). Median cycle numbers in A and B were six (1?6) and five (1?6). Dose intensities were comparable between arms. More patients in A received pemetrexed maintenance (24.2% versus 11.1%). With 16 (24.2%) in A and 19 (30.2%) patients in B achieving objective responses [odds ratio 0.74 (0.34?1.62), p?=?0.55] the primary endpoint was met. Overall survival was not different between arms (median 14.4 versus 14.9?months); [HR?=?1.07; (0.68?1.68), p?=?0.78]. Median progression-free survival was 7.0?months in A and 6.2?months in B [HR?=?1.63; (1.17?2.38); p?=?0.01]. Adverse events of CTCAE grade??3, particularly hematological, were more frequent in B. No difference in grade 4 and 5 infections between arms was noted. Treatment-related asthenia and nausea/vomiting of any grade were more frequent in A. Global health status, fatigue and constipation measured on day 1 of cycle 4 demonstrated superior scores in B.Conclusion:Pemetrexed and split-dose cisplatin is safe and effective. Advantages of split-dose cisplatin with regard to specific toxicities allow personalization of this important chemotherapy backbone.Trial Registration:European Clinical Trials Database (EudraCT) number 2011-001963-37.
Therapeutic advances in medical oncology Thousand Oaks, Calif. : Sage, 2009 13(2021) vom: Jan., Artikel-ID 1758835921996506, Seite 1-16 Online-Ressource
In dieser Arbeit wurde eine Methode zur systematischen Suche von Photokatalysatoren für die photolytische Wasserspaltung etabliert. Sie soll das Finden von Leitstrukturen für den effizienten Ablauf der kinetisch gehemmten Wasseroxidation beschleunigen. Deshalb wurden hier kombinatorische Methoden basierend auf Materialbibliotheken entwickelt. Hier wird ein neuer Präparationsweg für Materialbibliotheken beschrieben, der vorgeschlagene Weg garantiert homogenere Proben. Die Bibliothek wird mit einer optischen Sonde gescreent durch die gemessene photoelektrochemische Aktivität, kann das aktivste Material identifiziert werden. So konnten Materialbibliotheken des Zink-Eisensystems hergestellt werden und mit einem Screening in Abhängigkeit der Zusammensetzung für die Aktivität der Photoanode optimiert werden. Durch Vereinigung zweier Photoanoden auf einem Substrat konnte der vorhandene Aufbau genutzt werden, um die Aktivität dünner Schichtsysteme mit den Streueigenschaften des Materials zu korrelieren. <dt.>
In this work, a systematic methodology was established to evaluate photocatalysts towards photolytic water splitting by focusing on the search for lead structures that pave the way to accelerate the sluggish oxygen evolution reaction in an effective manner. Hence, combinatorial methods based on material libraries were developed. Here, a new preparation procedure for material libraries is described that guarantees homogenous samples. The library is screened with an optical probe the measured photo activity allows to identify the most active compound. By using the developed printing procedure material libraries of zinc iron system were prepared and screened towards the mixing ratio with the highest activity. By the unification of two photoanodes on one substrate the existing system was used to correlate activity with scattering properties of thin layers. <engl.>
von Jan Alexander Stratmann ; Sebastian Michels ; Sofia Emily Tsion Hornetz ; Daniel C. Christoph ; Sandra Sackmann ; Werner Spengle ; Helge Bischoff ; Monica Schäfer ; Jürgen Alt ; Annette Müller ; Eckart Laack ; Martin Kimmich ; Frank Griesinger ; Martin Sebastian
