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Adv Ther. 2019 Sep;36(9):2327-2341. doi: 10.1007/s12325-019-01034-0. Epub 2019 Jul 26.

Survival Analysis in Patients with Metastatic Merkel Cell Carcinoma Treated with Avelumab.

Author information

1
Evidera, London, UK. Tereza.Lanitis@evidera.com.
2
Evidera, Montreal, QC, Canada.
3
Evidera, London, UK.
4
Mapi, an ICON plc company, Munich, Germany.
5
EMD Serono Inc., Rockland, MA, USA.
6
Merck KGaA, Darmstadt, Germany.

Abstract

INTRODUCTION:

Complex underlying risk functions associated with immuno-oncology treatments have led to exploration of different methods (parametric survival, spline, landmark, and cure-fraction models) to estimate long-term survival outcomes. The objective of this study was to examine differences in estimated short- and long-term survival in previously treated metastatic Merkel cell carcinoma (mMCC) patients receiving avelumab, when using alternative extrapolation approaches.

METHODS:

Efficacy data from the phase 2 JAVELIN Merkel 200 trial (part A) with at least 12 months of follow-up were analyzed. Standard parametric survival analyses and analyses of overall survival (OS) as a function of surrogate outcomes comprised of response (landmark analyses) and progression-free survival plus post-progression survival (PFS + PPS) were used to project OS. Overall survival throughout lifetime was projected and compared with the observed OS data with at least 24 months of follow-up.

RESULTS:

Estimated OS from all three approaches provided a good fit to the observed OS curve from at least 12 months of follow-up. However, performance compared with OS data from at least 24 months showed that the landmark approach followed by PFS + PPS provided a better fit to the data as compared to standard parametric analysis. Mean life expectancy estimated with avelumab was 2.48 years with best-fitting parametric function (a log-normal distribution), 3.15 years with the landmark approach, and 3.54 years with PFS + PPS.

CONCLUSION:

Although standard parametric survival analysis may provide a good fit to short-term survival, it appears to underestimate the long-term survival benefits associated with avelumab in mMCC. Extrapolations based on surrogate outcomes of response or progression predict OS outcomes from longer follow-up better and appear to provide more clinically plausible projections.

FUNDING:

EMD Serono Inc, Rockland, MA, a business of Merck KGaA, Darmstadt, Germany.

KEYWORDS:

Avelumab; Extrapolation; Immuno-oncology; Landmark analyses; Merkel cell carcinoma; Overall survival; Post-progression survival; Standard parametric analysis

PMID:
31350728
DOI:
10.1007/s12325-019-01034-0

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