학술논문
Community-driven development of a modified progression-free survival ratio for precision oncology
Document Type
article
Author
Sebastian Schölch; Benedikt Brors; Albrecht Stenzinger; Ursula Ehmer; Ulrich-Frank Pape; Christoph Springfeld; Dirk Jäger; Felix J Hüttner; Andreas Mock; Christoph E Heilig; Simon Kreutzfeldt; Daniel Huebschmann; Christoph Heining; Evelin Schröck; Richard Schlenk; Hanno Glimm; Stefan Fröhling; Peter Horak; Leonidas Apostolidis; Marinela Augustin; Daniela Aust; Irfan Ahmed Bhatti; Johannes Bloehdorn; Cornelia Brendel; Christian Britschgi; Jan Braess; Stefan Burdach; Elena Busch; Jozefina Casuscelli; Alexander Desuki; Thomas Deutsch; Mareike Dietrich; Thomas J Ettrich; Johanna Falkenhorst; Tanja Fehm; Anne Flörcken; Andrea Forschner; Stefan Fuxius; Maria Gonzales-Carmona; Frank Griesinger; Sabine Grill; Stefan Gröschel; Georg Martin Haag; Ulrich Haag; Niels Halama; Holger Hebart; Nina Heidger; Barbara Hermes; Georg Hess; Simone Hettmer; Manuela Hoechstetter; Martin Hoffmann; Anna L Illert; Maximilian Jenzer; Bernd Kasper; Stefan Kasper-Virchow; Thomas Kindler; Ewa Koscielniak; Jan Krönke; Michael Kühn; Volker Kunzmann; Alois Lang; Jonas Leichsenring; Elisabeth Livingstone; Lucia Liotta; Kim Luley; Elisabeth Mack; Uwe M Martens; Klaus Metzeler; Jan Moritz Middeke; Lino Möhrmann; Roopa Jayarama-Naidu; Lukas Perkhofer; Arne Pfeufer; Constantin Pixberg; Michael Quante; Bernhard Rendenbach; Damian Rieke; Christian Rothermundt; Andre Norbert Sagerer; Martin Salzmann; Dieter Saur; Bastian Schilling; Jan Schleicher; Anke Schlenska-Lange; Thomas Schmidt; Sophia Schmitz; Rajiv Shah; Khalid Shoumariyeh; Alexander Siebenhüner; Martin Singh; Jens Siveke; Helen Starke; Sophia Strobel; Veronica Teleanu; Niklas Thon; Sebastian Wagner; Thomas Walle; Benedikt Westphalen; Bettina Whitlock; Eva Winkler; Naita Maren Wirsik; Lena Woydack; Angelika Zabel-du Bois; Stefanie Zschäbitz
Source
ESMO Open, Vol 4, Iss 6 (2019)
Subject
Language
English
ISSN
2059-7029
Abstract
Objective Measuring the success of molecularly guided therapies is a major challenge in precision oncology trials. A commonly used endpoint is an intra-patient progression-free survival (PFS) ratio, defined as the PFS interval associated with molecularly guided therapy (PFS2) divided by the PFS interval associated with the last prior systemic therapy (PFS1), above 1.3 or, in some studies, above 1.33 or 1.5.Methods To investigate if the concept of PFS ratios is in agreement with actual response evaluations by physicians, we conducted a survey among members of the MASTER (Molecularly Aided Stratification for Tumor Eradication Research) Programme of the German Cancer Consortium who were asked to classify the success of molecularly guided therapies in 194 patients enrolled in the MOSCATO 01 trial based on PFS1 and PFS2 times.Results A comparison of classification profiles revealed three distinct clusters of PFS benefit assessments. Only 29% of assessments were consistent with a PFS ratio threshold of 1.3, whereas the remaining 71% of participants applied a different classification scheme that did not rely on the relation between PFS times alone, but also took into account absolute PFS1 intervals. Based on these community-driven insights, we developed a modified PFS ratio that incorporates the influence of absolute PFS1 intervals on the judgement of clinical benefit by physicians. Application of the modified PFS ratio to outcome data from two recent precision oncology trials, MOSCATO 01 and WINTHER, revealed significantly improved concordance with physician-perceived clinical benefit and identified comparable proportions of patients who benefited from molecularly guided therapies.Conclusions The modified PFS ratio may represent a meaningful clinical endpoint that could aid in the design and interpretation of future precision oncology trials.