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Poster display session

3908 - Phase II study of individualized sunitinib (SUN) as first-line therapy for metastatic renal cell cancer: Pharmacokinetic data.

Date

10 Sep 2017

Session

Poster display session

Topics

Cytotoxic Therapy;  Renal Cell Cancer

Presenters

Georg Bjarnason

Citation

Annals of Oncology (2017) 28 (suppl_5): v295-v329. 10.1093/annonc/mdx371

Authors

G.A. Bjarnason1, J. Knox2, C.K. Kollmannsberger3, D. Soulieres4, D.S. Ernst5, P. Zalewski6, C.M. Canil7, E. Winquist8, S.J. Hotte9, S.A. North10, D.Y.C. Heng11, R.J. Macfarlane12, P.M. Venner13, A. Kapoor14, A.R. Hansen15, P. Czaykowski16, B. Boyd17, L. Wang18, N.S. Basappa19

Author affiliations

  • 1 Medical Oncology, Sunnybrook Odette Cancer Center, Sunnybrook HSC, M4N 3M5 - Toronto/CA
  • 2 Division Of Medical Oncology And Hematology, Princess Margaret Cancer Centre, Toronto/CA
  • 3 Department Of Oncology, British Columbia Cancer Agency, V5Z 4E6 - Vancouver/CA
  • 4 Oncology, Notre Dame du CHUM, H2L 4M1 - Montreal/CA
  • 5 Medical Oncology, London Regional Cancer Center, London Health Science Center, University of Western Ontario, N6A 4L6 - London/CA
  • 6 Medical Oncology, Durham Regional Cancer Centre, Oshawa/CA
  • 7 Medical Oncology, Ottawa Hospital Cancer Centre, K1H8L6 - Ottawa/CA
  • 8 Medical Oncology, London Health Science Centre, London/CA
  • 9 Medical Oncology, Juravinski Cancer Centre, L8V 5C2 - Hamilton/CA
  • 10 Oncology, University of Alberta, Cross Cancer Institute, Edmonton/CA
  • 11 Department Of Oncology, Tom Baker Cancer Centre, T2N 4N2 - Calgary/CA
  • 12 Medical Oncology, Queen Elizabeth II Health Centre, Halifax/CA
  • 13 Medical Oncology, Cross Cancer Institute, Edmonton/CA
  • 14 Surgical Oncology, Juravinski Cancer Centre, L8V 5C2 - Hamilton/CA
  • 15 Division Of Medical Oncology And Hematology, Princess Margaret Cancer Centre, M5G 1Z5 - Toronto/CA
  • 16 Hematology And Oncology, CancerCare Manitoba, R3E0V9 - Winnipeg/CA
  • 17 Data Management, Ozmosis Research, Toronto/CA
  • 18 Biostatistics Department, Princess Margaret Cancer Centre, M5G 2M9 - Toronto/CA
  • 19 Medical Oncology, University Of Alberta, Cross Cancer Institute, T6G1Z2 - Edmonton/CA
More

Resources

Abstract 3908

Background

Higher SUN exposure is associated with better outcomes but SUN PK on day 28 does not correlate with toxicity (# 363, ASCO-GU 2012).

Methods

Toxicity-driven dose/schedule individualization was tested in a prospective phase II study where all pts start on 50 mg/day (d). Pts with minimum toxicity on d 28 are dose escalated to 62.5 mg and then 75 mg. Samples for SU011248 and SU012662 were drawn on day 14 on the first course (100 pts) and again after the optimal dose/schedule had been established (58 pts). 11 patients had 2-3 more samples drawn during continued Rx on the optimal dose.

Results

117 pts were enrolled. Of 108 pts evaluable for response, dose was escalated in 20 pts to 62.5 mg (12 pts) and then to 75 mg (8 pts). In 49 pts eligible for dose reduction by standard criteria, a 50 mg dose was maintained but for 7 - 24 d. Dose was reduced to 37.5 mg in 22 pts and to 25 mg in 10 pts with individualized days on Rx. For 100 pts sampled on the first course the mean concentration (standard error) was 93.8 (3.0) and 29.8 (1.4) ng/mL for SU011248 and SU012662 respectively. For 58 pts, sampled again when optimal dose was established, the mean change from the 1st course for SU011248 and SU012662 was significantly different between dose levels (P 

Conclusions

While dose individualization corrects for some of the differences in PK values on the 1st Rx course, differences remain even after dose optimization emphasizing the importance of pharmacodynamics for toxicity and outcome. An ongoing dose optimization may be important to correct for the decline in PK over time.Table:

900P

Dose level (n pts)SU011248 (standard error)SU012662 (standard error)
During 1st course ng/mLDuring 1st course ng/mL
mean change at optimal dosemean change at optimal dose
50 mg (n = 27)90.7 (5.2)27.6 (2.6)
−11.8 (5.6)0 (2.3)
< 50 mg (n = 13)95.4 (10.1)33.6 (4.6)
−22.6 (12.7)−12.7 (4.4)
>50 mg (n = 18)77.1 (5.7)24.1 (2.6)
+29.6 (10.6)+12.4 (2.5)
After optimizationSU011248 (SE) at optimal doseSU012662 (SE) at optimal dose
50 mg (n = 27)78.9 (4.7)27.5 (2.3)
< 50 mg (n = 13)72.8 (8.0)21.7 (2.8)
>50 mg (n = 18)106.7 (11.9)36.5 (3.6)

Clinical trial identification

NCT01499121

Legal entity responsible for the study

Dr. Georg A Bjarnason and the Sunnybrook Research Institute

Funding

Pfizer Canada

Disclosure

G.A. Bjarnason: Funding for this trial from Pfizer. Honoraria and support to attend meetings from Pfizer. C.K. Kollmannsberger: Pfizer: adboards, honoraria for presentations, participation in clinical trials. D. Soulieres: Pfizer Ad boards and honorarium for talks. P. Zalewski: Pfizer Advisory boards. C.M. Canil, R.J. Macfarlane: Pfizer advisory boards. S.J. Hotte: Pfizer advisory boards and CME talks. S.A. North: Honoraria from Pfizer. D.Y.C. Heng: Advisory boards: Pfizer, Novartis, Bristol-Myers Squib. A. Kapoor: Pfizer advisory boards and CME talks. A.R. Hansen: Advisory board with Pfizer. N.S. Basappa: Pfizer honoraria, advisory boards, travel support. All other authors have declared no conflicts of interest.

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