S Négrier1, A G Bushmakin2, J C Cappelleri2, B Korytowsky3, R Sandin4, C Charbonneau5, M D Michaelson6, R A Figlin7, R J Motzer8. 1. Université de Lyon, Centre Léon Bérard, 28, rue Laennec, F-69373 Lyon Cedex 08, France. Electronic address: sylvie.negrier@lyon.unicancer.fr. 2. Statistics, Pfizer Inc., 445 Eastern Point Road, Groton, CT 06340, USA. 3. Global Health Economics and Outcomes Research, Pfizer Oncology, 235 E 42nd St, New York, NY 10017, USA. 4. Global Health Economics and Outcomes Research, Pfizer Oncology, Vetenskapsvägen 10, Sollentuna 10191, Sweden. 5. Global Outcomes Research, Specialty Care BU, Pfizer P.I.O., 23-25, avenue du Dr. Lannelongue, 75014 Paris, France. 6. Massachusetts General Hospital Cancer Center, 55 Fruit Street, YAW 7, Boston, MA 02114, USA. 7. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Saperstein Critical Care Tower, 1S28, Los Angeles, CA 90048, USA. 8. Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA.
Abstract
BACKGROUND: To determine suitability of progression-free survival (PFS) as a surrogate end-point for overall survival (OS), we evaluated the relationship between PFS and OS in 750 treatment-naïve metastatic renal cell carcinoma (mRCC) patients who received sunitinib or interferon-alpha (IFN-α) in a phase III study. METHODS: The relationship between PFS and post-progression survival (PPS; the difference between PFS and OS) was studied, which correctly removes inherent dependencies between PFS and OS, to properly estimate whether and to what extent PFS can serve as a surrogate for OS. A Weibull parametric model to failure time data was fit to determine whether longer PFS was significantly and meaningfully predictive of longer PPS. In a sensitivity analysis by Kaplan-Meier non-parametric method, PPS curves for three approximately equal numbered groups of patients categorised by PFS were compared by log-rank test. RESULTS: In the Weibull parametric model, longer PFS was significantly predictive of longer PPS (P<0.001). The model also allowed prediction of estimated median PPS duration from actual PFS times. In the Kaplan-Meier (non-parametric) analysis, incrementally longer PFS was also associated with longer PPS, and the PPS curves for the three PFS groups were significantly different (P<0.0001). CONCLUSIONS: A positive relationship was found between PFS and PPS duration in individual mRCC patients randomised to first-line treatment with sunitinib or IFN-α. These results indicate that PFS can act as a surrogate end-point for OS in the first-line mRCC setting and provide clinical researchers with a potentially useful approach to estimate median PPS based on PFS.
BACKGROUND: To determine suitability of progression-free survival (PFS) as a surrogate end-point for overall survival (OS), we evaluated the relationship between PFS and OS in 750 treatment-naïve metastatic renal cell carcinoma (mRCC) patients who received sunitinib or interferon-alpha (IFN-α) in a phase III study. METHODS: The relationship between PFS and post-progression survival (PPS; the difference between PFS and OS) was studied, which correctly removes inherent dependencies between PFS and OS, to properly estimate whether and to what extent PFS can serve as a surrogate for OS. A Weibull parametric model to failure time data was fit to determine whether longer PFS was significantly and meaningfully predictive of longer PPS. In a sensitivity analysis by Kaplan-Meier non-parametric method, PPS curves for three approximately equal numbered groups of patients categorised by PFS were compared by log-rank test. RESULTS: In the Weibull parametric model, longer PFS was significantly predictive of longer PPS (P<0.001). The model also allowed prediction of estimated median PPS duration from actual PFS times. In the Kaplan-Meier (non-parametric) analysis, incrementally longer PFS was also associated with longer PPS, and the PPS curves for the three PFS groups were significantly different (P<0.0001). CONCLUSIONS: A positive relationship was found between PFS and PPS duration in individual mRCC patients randomised to first-line treatment with sunitinib or IFN-α. These results indicate that PFS can act as a surrogate end-point for OS in the first-line mRCC setting and provide clinical researchers with a potentially useful approach to estimate median PPS based on PFS.
Authors: Aracelis Z Torres; Nathan C Nussbaum; Christina M Parrinello; Ariel B Bourla; Bryan E Bowser; Samuel Wagner; David C Tabano; Daniel George; Rebecca A Miksad Journal: Adv Ther Date: 2022-04-17 Impact factor: 4.070