839P - Phase II study of individualized sunitinib as first-line therapy for metastatic clear cell renal cell cancer (mRCC)

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Renal Cell Cancer
Presenter Georg Bjarnason
Citation Annals of Oncology (2014) 25 (suppl_4): iv280-iv304. 10.1093/annonc/mdu337
Authors G.A. Bjarnason1, B. Naveen2, E. Winquist3, C.K. Kollmannsberger4, C. Canil5, S. North6, D.S. Ernst3, R.J. Macfarlane7, D. Heng8, P. Zalewski9, S.J. Hotte10, D. Soulieres11, P. Venner2, I.F. Tannock12, M.N. Reaume5, A. Kapoor10, B.J. Eigl13, D.J. Ruether8, B. Boyd14, J. Knox15
  • 1Medical Oncology, Sunnybrook Odette Cancer Centre, M4N 3M5 - Toronto/CA
  • 2Medical Oncology, Cross Cancer Institute, T6G 1Z2 - Edmonton/CA
  • 3Medical Oncology, London Regional Cancer Center, CA-N6A 4L6 - London/CA
  • 4Medical Oncology, British Columbia Cancer Agency, V5Z 4E6 - Vancouver/CA
  • 5Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa/CA
  • 6Medical Oncology, Cross Cancer Institute, Edmonton/CA
  • 7Medical Oncology, QE2 Health Sciences Centre, Halifax/CA
  • 8Medical Oncology, Tom Baker Cancer Centre, Calgary/CA
  • 9Medical Oncology, Durham Regional Cancer Centre, Oshawa/CA
  • 10Medical Oncology, Juravinski Cancer Centre, Hamilton/CA
  • 11Departement Of Medicine, CHUM Hôpital Notre-Dame, Montreal/CA
  • 12Dept Of Medical Oncology, Princess Margaret Hospital, M5G 2M9 - Toronto/CA
  • 13Oncology, British Columbia Cancer Agency, V5Z 4E6 - Vancouver/CA
  • 14Clinical Trials, Ozmosis Research Inc, Toronto/CA
  • 15Dept. Of Medical Oncology And Hematology, Princess Margaret Hospital, M5G 2M9 - Toronto/CA

Abstract

Aim

A high sunitinib area under the curve is associated with more toxicity, and a better response rate (RR), progression free (PFS) and overall survival (OS). Retrospective data (Urol Oncol 2014;32:480) show poorer PFS and OS in mRCC patients (pts) with minimum toxicity on the standard 28 day (d)/14 d schedule vs. pts with toxicity leading to schedule and/or dose changes. We hypothesized that toxicity (mucositis, diarrhea, hand foot syndrome, fatigue, hematological) could serve as a surrogate to individualize therapy (Rx) to optimize drug exposure and manage toxicity for each pt.

Methods

A prospective phase II study (same eligibility criteria as EFFECT trial) will enter 110 pts with the primary endpoint of improving PFS from 8.5 (EFFECT) to 14 Months. Pts start on a 50 mg dose with the intent to treat for 28 d with the Rx break reduced to 7 d for all Rx schedules. Pts with grade-2 toxicity by d 28 stay on the 28 d schedule. Patients with > grade-2 toxicity on d 28 on the first course continue Rx on a 50 mg dose with the number of d on Rx individually reduced aiming for ≤ grade-2 toxicity. Dose is reduced to 37.5 mg in pts that cannot tolerate 50 mg for at least 7 d and to 25 mg in pts that cannot tolerate 37.5 mg for at least 7 d with individualized duration of Rx based on toxicity. Pts with minimum toxicity on d 28 on the first course are dose escalated to 62.5 mg and then 75 mg on a 14 d /7 d schedule.

Results

With 73 pts on study, dose and schedule data are available for 69 pts with 13 pts (18.8%) dose escalated to 62.5 mg (9 pts) and 75 mg (4 pts). In 33 pts (47.8%), that would have been dose reduced by standard criteria, a 50 mg dose was continued but for fewer d (7-16 d) and 13 pts (18.8%) stayed on a 28d/7d schedule. Dose was reduced to 37.5 mg in 6 pts (8.7% vs. 36 - 63% in 4 large trials) and to 25 mg in 4 pts (5.8 % vs. 15 - 19% in 4 trials). Rx was discontinued due to toxicity in 3 pts (4.3% vs. 15-19% in 4 trials). In 61 evaluable pts, we found complete responses (CR) in 3 pts, partial responses (PR) in 27 pts, stable disease (SD) > 3 months in 23 pts (< 3 months in 2 pts) and progression in 6 pts (9.8% vs. 24.6% in EFFECT) for a CR + PR rate of 49.2% (vs. 32% in EFFECT 4/2 arm) and CR + PR + SD rate of 86.9% (vs. 75% in EFFECT).

Conclusions

Individualized sunitinib dosing is safe and feasible in a multicenter setting and associated with improved dose intensity and a good response rate.

Disclosure

G.A. Bjarnason: Pfizer - membership on an advisory board - Pfzer-sponsored research - Support to attend meetings; B. Naveen, C. Canil, S. North, D. Heng, P. Zalewski, D. Soulières, D.J. Ruether, M.N. Reaume and A. Kapoor: Pfizer member on advisory boards; P. Venner: Pfizer member on advisory boards and sponsored research; C.K. Kollmannsberger: Pfizer membership on an advisory board; B.J. Eigl: Pfizer: consultancy, honoraria, research funding; J. Knox: Pfizer grant support. All other authors have declared no conflicts of interest.