JTO Clinical and Research Reports (Apr 2024)
Checkpoint Inhibitor Monotherapy in Potentially Trial-Eligible or Trial-Ineligible Patients With Metastatic NSCLC in the German Prospective CRISP Registry Real-World Cohort (AIO-TRK-0315)
- Frank Griesinger, MD, PhD,
- Wilfried E.E. Eberhardt, MD, PhD,
- Wolfgang M. Brueckl, MD, PhD,
- Horst-Dieter Hummel, MD, PhD,
- Bastian Jaeschke, MD,
- Jens Kern, MD,
- Claas Wesseler, MD,
- Martina Jänicke, PdD,
- Annette Fleitz, PhD,
- Stefan Zacharias, PhD,
- Annette Hipper, PhD,
- Annika Groth, MD, PhD,
- Wilko Weichert, MD, PhD,
- Steffen Dörfel,
- Volker Petersen, MD,
- Jan Schröder, MD,
- Jochen Wilke, MD,
- Martin Sebastian, MD,
- Michael Thomas, MD, PhD,
- Juliana Ababei,
- Jürgen Alt,
- Andreas Ammon,
- Jürgen Anhuf,
- Ivo Azeh,
- Stefan Bauer,
- Dirk Behringer,
- Winfried Berger,
- Christiane Bernhardt,
- Mathias Bertram,
- Michael Boesche,
- Sabine Bohnet,
- Harald-Robert Bruch,
- Wolfgang Brückl,
- Ulrike Burkhard-Meier,
- Petros Christopoulos,
- Klaus-Ulrich Däßler,
- Maike de Wit,
- Tobias Dechow,
- Reinhard Depenbusch,
- Lutz Dietze,
- Markus Dommach,
- Steffen Dörfel,
- Wilfried Eberhardt,
- Corinna Elender,
- Wolfgang Elsel,
- Till-Oliver Emde,
- Martin Faehling,
- Thomas Fietz,
- Jürgen R. Fischer,
- Dimitri Flieger,
- Anke Freidt,
- Werner Freier,
- Christian Frenzel,
- Florian Fuchs,
- Roswitha Fuchs,
- Tobias Gaska,
- Wolfgang Gleiber,
- Christian Grah,
- Frank Griesinger,
- Christian Grohé,
- Matthias Groschek,
- Björn Güldenzoph,
- Andreas Günther,
- Siegfried Haas,
- Matthias Hackenthal,
- Volker Hagen,
- Lars Hahn,
- Verena Hannig Carla,
- Richard Hansen,
- Hanns-Detlev Harich,
- Monika Heilmann,
- Kathrin Heinrich,
- Christiane Hering-Schubert,
- Jörg Heßling,
- Petra Hoffknecht,
- Patricia Hortig,
- Gerdt Hübner,
- Horst-Dieter Hummel,
- Ulrich Hutzschenreuter,
- Thomas Illmer,
- Georg Innig,
- Bastian Jaeschke,
- Christian Junghanß,
- Ulrich Kaiser,
- Haytham Kamal,
- Kato Kambartel,
- Jens Kern,
- Martin Kimmich,
- Dorothea Kingreen,
- Heinz Kirchen,
- Martine Klausmann,
- Ortwin Klein,
- Konrad Kokowski,
- Wolfgang Körber,
- Cornelius Kortsik,
- Dirk Koschel,
- Benoit Krämer,
- Beate Krammer-Steiner,
- Eckart Laack,
- Christof Lamberti,
- Rumo David Leistner,
- Christoph Losem,
- Andreas Lück,
- Christoph Maintz,
- Kerstin Martin,
- Dirk Medgenberg,
- Martin Metzenmacher,
- Christian Meyer zum Büschenfelde,
- Philipp Meyn,
- Enno Moorahrend,
- Annette Müller,
- Lothar Müller,
- Michael Neise,
- Holger Nückel,
- Arnd Nusch,
- Tobias Overbeck,
- Henning Pelz,
- Volker Petersen,
- Bettina Peuser,
- Margarete Plath,
- Winfried J. Randerath,
- Jacqueline Rauh,
- Martin Reck,
- Dietmar Reichert,
- Niels Reinmuth,
- Marcel Reiser,
- Roland Repp,
- Daniel Reschke,
- Achim Rittmeyer,
- Yolanda Rodemer,
- Sandra Sackmann,
- Parvis Sadjadian,
- Reiner Sandner,
- Annette Sauer,
- Harald Schäfer,
- Christoph Schaudt,
- Rudolf Schlag,
- Burkhard Schmidt,
- Stephan Schmitz,
- Jan Schröder,
- Michael Schroeder,
- Mathias Schulze,
- Christian Schumann,
- Wolfgang Schütte,
- Martin Schwaiblmair,
- Florian Schwindt Peter,
- Martin Sebastian,
- Bernd Seese,
- Gernot Seipelt,
- Thomas Sorgenfrei,
- Johannes Steiff,
- Heike Steiniger,
- Tanja Trarbach,
- Amanda Tufman,
- Jens Uhlig,
- Ursula Vehling-Kaiser,
- Eyck von der Heyde,
- Ulla von Verschuer,
- Cornelius Waller,
- Thomas Wehler,
- Georg Weißenborn,
- Florian Weißinger,
- Martin Wermke,
- Claas Wesseler,
- Jörg Wiegand,
- Stefan Wilhelm,
- Jochen Wilke,
- Mark-Oliver Zahn,
- Matthias Zaiss,
- Matthias Zeth
Affiliations
- Frank Griesinger, MD, PhD
- Department of Hematology and Oncology, University Department Internal Medicine-Oncology, Pius-Hospital, University Medicine Oldenburg, Oldenburg, Germany; Corresponding author. Address for correspondence: Frank Griesinger, MD, PhD, Department of Hematology and Oncology, Pius-Hospital, University Medicine Oldenburg, Georgstraße 12, 26121 Oldenburg, Germany.
- Wilfried E.E. Eberhardt, MD, PhD
- Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; Division of Thoracic Oncology, West German Cancer Center, University Medicine Essen - Ruhrlandklinik, Essen, Germany
- Wolfgang M. Brueckl, MD, PhD
- Department of Respiratory Medicine, Allergology and Sleep Medicine, Paracelsus Medical University, General Hospital Nuremberg, Nuremberg, Germany
- Horst-Dieter Hummel, MD, PhD
- Translational Oncology/Early Clinical Trial Unit (ECTU), Comprehensive Cancer Center Mainfranken and Bavarian Cancer Research Center (BZKF), University Hospital Würzburg, Würzburg, Germany
- Bastian Jaeschke, MD
- HELIOS Dr. Horst Schmidt Kliniken Wiesbaden, IM III: Hämatologie, Onkologie, Palliativmedizin, Interdisziplinäre Onkologische Ambulanz, Wiesbaden, Germany
- Jens Kern, MD
- Klinikum Würzburg Mitte, Missioklinik, Medizinische Klinik – Schwerpunkt Pneumologie und Beatmungsmedizin, Würzburg, Germany
- Claas Wesseler, MD
- Asklepios Tumorzentrum Hamburg, Klinikum Harburg, Lungenabteilung, Hamburg, Germany
- Martina Jänicke, PdD
- Clinical Epidemiology and Health Economics, iOMEDICO, Freiburg, Germany
- Annette Fleitz, PhD
- Clinical Epidemiology and Health Economics, iOMEDICO, Freiburg, Germany
- Stefan Zacharias, PhD
- Biostatistics, iOMEDICO, Freiburg, Germany
- Annette Hipper, PhD
- AIO-Studien-gGmbH, Berlin, Germany
- Annika Groth, MD, PhD
- AIO-Studien-gGmbH, Berlin, Germany
- Wilko Weichert, MD, PhD
- Institute of Pathology, School of Medicine, Technical University of Munich, Munich, Germany
- Steffen Dörfel
- Onkozentrum Dresden/Freiberg/Meißen, Dresden, Germany
- Volker Petersen, MD
- Onkologische Schwerpunktpraxis Dr. med. Volker Petersen, Heidenheim a.d.B, Germany
- Jan Schröder, MD
- Gemeinschaftspraxis für Hämatologie und internistische Onkologie, Mülheim a.d.R., Germany
- Jochen Wilke, MD
- Schwerpunktpraxis Hämatologie & Internistische Onkologie, Fürth, Germany
- Martin Sebastian, MD
- Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Germany; Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt, Germany
- Michael Thomas, MD, PhD
- Department of Thoracic Oncology, Thoraxklinik, University Hospital Heidelberg and Translational, Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
- Juliana Ababei
- Jürgen Alt
- Andreas Ammon
- Jürgen Anhuf
- Ivo Azeh
- Stefan Bauer
- Dirk Behringer
- Winfried Berger
- Christiane Bernhardt
- Mathias Bertram
- Michael Boesche
- Sabine Bohnet
- Harald-Robert Bruch
- Wolfgang Brückl
- Ulrike Burkhard-Meier
- Petros Christopoulos
- Klaus-Ulrich Däßler
- Maike de Wit
- Tobias Dechow
- Reinhard Depenbusch
- Lutz Dietze
- Markus Dommach
- Steffen Dörfel
- Wilfried Eberhardt
- Corinna Elender
- Wolfgang Elsel
- Till-Oliver Emde
- Martin Faehling
- Thomas Fietz
- Jürgen R. Fischer
- Dimitri Flieger
- Anke Freidt
- Werner Freier
- Christian Frenzel
- Florian Fuchs
- Roswitha Fuchs
- Tobias Gaska
- Wolfgang Gleiber
- Christian Grah
- Frank Griesinger
- Christian Grohé
- Matthias Groschek
- Björn Güldenzoph
- Andreas Günther
- Siegfried Haas
- Matthias Hackenthal
- Volker Hagen
- Lars Hahn
- Verena Hannig Carla
- Richard Hansen
- Hanns-Detlev Harich
- Monika Heilmann
- Kathrin Heinrich
- Christiane Hering-Schubert
- Jörg Heßling
- Petra Hoffknecht
- Patricia Hortig
- Gerdt Hübner
- Horst-Dieter Hummel
- Ulrich Hutzschenreuter
- Thomas Illmer
- Georg Innig
- Bastian Jaeschke
- Christian Junghanß
- Ulrich Kaiser
- Haytham Kamal
- Kato Kambartel
- Jens Kern
- Martin Kimmich
- Dorothea Kingreen
- Heinz Kirchen
- Martine Klausmann
- Ortwin Klein
- Konrad Kokowski
- Wolfgang Körber
- Cornelius Kortsik
- Dirk Koschel
- Benoit Krämer
- Beate Krammer-Steiner
- Eckart Laack
- Christof Lamberti
- Rumo David Leistner
- Christoph Losem
- Andreas Lück
- Christoph Maintz
- Kerstin Martin
- Dirk Medgenberg
- Martin Metzenmacher
- Christian Meyer zum Büschenfelde
- Philipp Meyn
- Enno Moorahrend
- Annette Müller
- Lothar Müller
- Michael Neise
- Holger Nückel
- Arnd Nusch
- Tobias Overbeck
- Henning Pelz
- Volker Petersen
- Bettina Peuser
- Margarete Plath
- Winfried J. Randerath
- Jacqueline Rauh
- Martin Reck
- Dietmar Reichert
- Niels Reinmuth
- Marcel Reiser
- Roland Repp
- Daniel Reschke
- Achim Rittmeyer
- Yolanda Rodemer
- Sandra Sackmann
- Parvis Sadjadian
- Reiner Sandner
- Annette Sauer
- Harald Schäfer
- Christoph Schaudt
- Rudolf Schlag
- Burkhard Schmidt
- Stephan Schmitz
- Jan Schröder
- Michael Schroeder
- Mathias Schulze
- Christian Schumann
- Wolfgang Schütte
- Martin Schwaiblmair
- Florian Schwindt Peter
- Martin Sebastian
- Bernd Seese
- Gernot Seipelt
- Thomas Sorgenfrei
- Johannes Steiff
- Heike Steiniger
- Tanja Trarbach
- Amanda Tufman
- Jens Uhlig
- Ursula Vehling-Kaiser
- Eyck von der Heyde
- Ulla von Verschuer
- Cornelius Waller
- Thomas Wehler
- Georg Weißenborn
- Florian Weißinger
- Martin Wermke
- Claas Wesseler
- Jörg Wiegand
- Stefan Wilhelm
- Jochen Wilke
- Mark-Oliver Zahn
- Matthias Zaiss
- Matthias Zeth
- Journal volume & issue
-
Vol. 5,
no. 4
p. 100626
Abstract
Introduction: Patients with metastatic NSCLC (mNSCLC) treated with immune checkpoint inhibitors in clinical practice may often not meet the strict inclusion criteria of clinical trials. Our aim was to assess the trial eligibility of patients with mNSCLC treated with pembrolizumab monotherapy in real-world and to compare the outcome of “trial-ineligible” and “potentially trial-eligible” patients. Methods: Data from the prospective, clinical research platform CRISP were used to compare patient characteristics, treatment, and outcome of patients with programmed cell death-ligand 1 tumor proportion score greater than or equal to 50% tumors treated with pembrolizumab monotherapy who are deemed either “potentially trial-eligible” or “trial-ineligible” according to inclusion and exclusion criteria of the registrational studies (KEYNOTE-024 and -042). Results: Of 746 patients included, 343 patients (46.0%) were classified as “trial-ineligible” and had significantly worse outcomes compared with “potentially trial-eligible” patients (n = 403, 54.0%): median progression-free survival: 6.2 (95% confidence interval [CI]: 5.2–8.4) versus 10.3 (95% CI: 8.4–13.8) months, hazard ratio (trial-ineligible versus potentially trial-eligible) of 1.43 (95% CI: 1.19–1.72), p less than 0.001; median overall survival: 15.9 (95% CI: 11.4–20.3) versus 25.3 (95% CI: 19.8–30.4) months, hazard ratio of 1.36 (95% CI: 1.10–1.67), p equals 0.004. Conclusions: Our data reveal that a considerable proportion of patients with mNSCLC are not eligible to participate in a clinical trial and were found to have worse outcomes than potentially trial-eligible patients, whose outcomes were comparable with those obtained from pivotal clinical trials. This is of substantial clinical relevance for physicians discussing outcomes to be expected with their patients and stresses the need for real-world effectiveness analyses.