819P - Hypertension, neutropenia, thrombocytopenia, normal sodium and LDH within the first 12 weeks of treatment as independent biomarkers of outcome in m...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Renal Cell Cancer
Complications of Treatment
Presenter Anne Soerensen
Citation Annals of Oncology (2014) 25 (suppl_4): iv280-iv304. 10.1093/annonc/mdu337
Authors A.V. Soerensen1, P.F. Geertsen2, I.J. Christensen3, G.G. Hermann4, N.V. Jensen5, K. Fode6, A. Petersen7, R. Sandin8, F. Donskov6
  • 1Department Of Oncology, University Hospital of Copenhagen Herlev, 2730 - Herlev/DK
  • 2Department Of Oncology, Herlev University Hospital, 2730 - Herlev/DK
  • 3Finsen Laboratory And Biotech Research And Innovation Centre (bric), Rigshospitalet and University of Copenhagen, 2300 - Copenhagen/DK
  • 4Department Of Urology, University Hospital of Copenhagen Rigshospitalet, 2100 - Copenhagen/DK
  • 5Department Of Oncology, Odense University Hospital, 5000 - Odense/DK
  • 6Department Of Oncology, Aarhus University Hospital, 8000 - Aarhus/DK
  • 7Department Of Pathology, Aalborg University Hospital, 9100 - Aalborg/DK
  • 8Oncology, Pfizer, 19190 - Sollentuna/SE

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Abstract

Aim

Treatment-related hypertension and neutropenia are biomarkers of outcome in patients with mRCC. Other biomarkers are needed.

Methods

Baseline Heng risk group status and time-dependent biomarkers within the first 12 weeks after treatment initiation were analyzed with univariate and multivariate Cox proportional hazard model in a complete national cohort of all Danish mRCC patients receiving first line tyrosinekinase-inhibitors (TKI) or interleukin-2 based immunotherapy (IT) from 2006 – 2010. Measurements were made day 1 of each cycle after the first cycle.

Results

735 patients received first line TKI (59%) or IT (41%). Overall median survival (OS) was 14.0 months and median OS for baseline Heng favourable, intermediate and poor risk groups were 33.4, 18.5 and 5.8 months, respectively (p < 0.0001). Systolic blood pressure ≥ 140 mmHg, neutrophils < lower level of normal (LLN), platelets < LLN, sodium > LLN and LDH < 1.5 x upper level of normal were significantly associated with favourable OS independent of baseline Heng risk group status in multivariate analyses stratified for TKI and IT (p ≤ 0.04 for these analyses). For patients with a good (3-5 factors) and poor (0-2 factors) biomarker profile median OS were 23.5 and 9.6 months, respectively (p < 0.0001). Adding the 5-factor biomarker profile to Heng risk groups provided significantly improved prognostication of patients in Heng intermediate and poor risk groups, Table 1.

OS per biomarker profile within 12 weeks treatment for baseline Heng risk group status

Favourable Intermediate Poor
Biomarker profile N OS 95% CI p value N OS 95% CI p value N OS 95% CI p value
Good 40 38.9 29.7-NA 0.112 175 25.7 20.9-33.6 <0.0001 67 12.8 10.7-19.8 <0.0001
Poor 17 28.7 23.4-NA 77 12.0 7.9-16.5 86 6.4 5.2-10.8

This table contains 462 patients with complete data; OS = Overall Survival (months); N = Number; CI = Confidence interval; NA = Not applicable.

Conclusions

Hypertension, neutropenia, thrombocytopenia, normal sodium, and LDH within the first 12 weeks of treatment are independent biomarkers of favourable outcome in mRCC and provide additional prognostic information for patients in Heng intermediate and poor risk groups. These biomarkers seem independent of treatment type.

Disclosure

A.V. Soerensen: has received research funding from Pfizer; R. Sandin: is a fulltime employee at Pfizer and has stock ownership; F. Donskov: has received a research grant from Novartis and GSK. All other authors have declared no conflicts of interest.