Related Experiment Video
Updated: Mar 9, 2026
Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
Published on: February 12, 2017
Thirty-Month Complete Response as a Surrogate End Point in First-Line Follicular Lymphoma Therapy: An Individual
Qian Shi1, Christopher R Flowers1, Wolfgang Hiddemann1
1Qian Shi and Daniel J. Sargent, Mayo Clinic, Rochester; Bruce A. Peterson, University of Minnesota, Minneapolis, MN; Christopher R. Flowers, Winship Cancer Institute of Emory University, Atlanta, GA; Wolfgang Hiddemann and Eva Hoster, Ludwig-Maximilians University Hospital, Munich; Michael Herold, HELIOS Kliniken, Erfurt, Germany; Robert Marcus, Addenbrooke's Hospital, Cambridge, United Kingdom; Anton Hagenbeek, Academic Medical Center, Amsterdam, the Netherlands; Eva Kimby, Karolinska Institutet, Stockholm, Sweden; Howard Hochster, Yale Cancer Center, New Haven, CT; Umberto Vitolo, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin; Marco Ladetto, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy; Emmanuel Gyan, University Hospital, Tours; Franck Morschhauser, Service Université de Lille 2, Lille; Gilles Salles, Université Claude Bernard, Pierre Bénite, France; Michele Ghielmini and Emanuele Zucca, Oncology Institute of Southern Switzerland, Bellinzona; Michele Ghielmini and Emanuele Zucca, Swiss Group for Clinical Cancer Research, Bern; Tina Nielsen, F. Hoffmann-La Roche, Basel; Sabine De Bedout, Celgene, Boudry, Switzerland; Tommy Fu, Celgene, Summit, NJ; Nancy Valente, Genentech, South San Francisco, CA; and Nathan H. Fowler, University of Texas MD Anderson Cancer Center, Houston, TX.
Complete response at 30 months (CR30) can serve as a surrogate end point for progression-free survival (PFS) in follicular lymphoma (FL) trials. This finding may accelerate the development of novel FL therapies for patients.
Area of Science:
- Hematology
- Clinical Trials
- Oncology
Background:
- Follicular lymphoma (FL) is an indolent cancer with limited curative options.
- Current first-line therapy trials rely on progression-free survival (PFS), a lengthy endpoint requiring over 7 years of follow-up.
- Expediting clinical trials is crucial for patient access to novel treatments.
Purpose of the Study:
- To validate complete response at 30 months (CR30) as a surrogate endpoint for PFS in first-line FL therapy.
- To assess if CR30 can predict treatment effects on PFS, thereby shortening trial durations.
Main Methods:
- Pooled analysis of individual patient data from 13 randomized multicenter trials (post-1990) in first-line FL therapy.
- Evaluated the correlation between CR30 odds ratio and PFS hazard ratio using linear regression (R²WLS) and bivariate copula (R²Copula) models.
- Applied prespecified criteria for surrogacy (R² ≥ 0.80, lower-bound 95% CI > 0.60).
Main Results:
- Analysis included 3,837 patients from eight induction and five maintenance trials.
- The prespecified surrogacy threshold was met: R²WLS = 0.88 (95% CI, 0.77-0.96) and R²Copula = 0.86 (95% CI, 0.72-1.00).
- A 11% absolute improvement in CR30 predicted a significant PFS treatment effect (hazard ratio, 0.69).
Conclusions:
- Complete response at 30 months (CR30) is a validated surrogate endpoint for PFS in first-line FL treatment trials.
- Utilizing CR30 can significantly expedite the development and approval of novel therapies for FL patients.
- This surrogate endpoint allows for earlier patient access to innovative treatments, years ahead of traditional PFS maturation.
