Assessment of progression-free survival as a surrogate end-point for overall survival in patients with metastatic renal cell carcinoma.
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.
Université de Lyon, Centre Léon Bérard, 28, rue Laennec, F-69373 Lyon Cedex 08, France. Electronic address: sylvie.negrier@lyon.unicancer.fr.
S
S
Négrier
Statistics, Pfizer Inc., 445 Eastern Point Road, Groton, CT 06340, USA.
A G
AG
Bushmakin
Statistics, Pfizer Inc., 445 Eastern Point Road, Groton, CT 06340, USA.
J C
JC
Cappelleri
Global Health Economics and Outcomes Research, Pfizer Oncology, 235 E 42nd St, New York, NY 10017, USA.
B
B
Korytowsky
Global Health Economics and Outcomes Research, Pfizer Oncology, Vetenskapsvägen 10, Sollentuna 10191, Sweden.
R
R
Sandin
Global Outcomes Research, Specialty Care BU, Pfizer P.I.O., 23-25, avenue du Dr. Lannelongue, 75014 Paris, France.
C
C
Charbonneau
Massachusetts General Hospital Cancer Center, 55 Fruit Street, YAW 7, Boston, MA 02114, USA.
M D
MD
Michaelson
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Saperstein Critical Care Tower, 1S28, Los Angeles, CA 90048, USA.
R A
RA
Figlin
Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA.
R J
RJ
Motzer
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018572:Disease-Free Survival; D023381:Endpoint Determination; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015337:Multicenter Studies as Topic; D011758:Pyrroles / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D000077210:Sunitinib; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007211:Indoles; D016898:Interferon-alpha; D011758:Pyrroles; D000077210:Sunitinib
Overall survival; Progression-free survival; Renal cell carcinoma; Sunitinib; Surrogate end-point