Management and outcome of venous thromboembolic events (VTEs) during sunitinib treatment

Abstract

14625 Background: Sunitinib (SU) is a multi target tyrosine kinase inhibitor approved by FDA and EMEA in Renal Cell Cancer (RCC) and Gastric intestinal stromal tumor (GIST). SU has not been reported to increase the rate of VTEs in RCC, GIST. VTEs’ management and outcome under SU treatment is unknown. We reviewed cases of VTEs in RCC, GIST and NSCLC pts treated with SU. Methods: RCC, GIST and NSCLC pts treated with SU in prospective clinical trials at Institut Gustave Roussy (IGR) were analyzed to assess the risk of VTEs rate and identify predisposing factors. SU was given at 50 mg/d 4 wks out of 6, as a 2nd or 3rd line in GIST, as maintenance therapy after 4 cycles of paclitaxel-carboplatin in NSCLC and in RCC pts after cytokine failure. Key exclusions criteria of these trials were: pts with history of thrombosis within 6 months, brain metastasis, PS WHO>1, or squamous cell lung cancer. Diagnoses of symptomatic pulmonary embolism (PE) confirmed by CT pulmonary angiography were centrally reviewed. Results: Between Aug.05 and Oct.06, 72 pts were included (21 GIST, 8 NSCLC, 43 RCC). Baseline characteristics were (RCC/GIST/NSCLC): female 23%/57%/50%, mean age 54/54/51yrs, PS 0: 84%/57%/38%, indwelling central venous catheters (ICVC) 0%/0%/100%, bone metastases: 11%/0%/75%, liver metastases: 76 %/28%/37%. None has history of previous cancer or surgery within 1 yr. Five pts (6.9%, 95%CI: 3.0–15.2%) developed symptomatic PE., 3 in NSCLC pts (37%), 1 in RCC (2%) and 1 in GIST (5%). PE occurred early aftersunitinib initiation (4 wks in 2 pts, 6 wks in 2 pts, 10 wks in 1 pt). In case of PE, SU was interrupted in NSCLC but continued in GIST and RCC pts. All 5 PE were treated with low molecular weight heparin (LMWH). In 1 pt (GIST), LMWH was discontinued after 4 months due to a grade 3 esophageal hemorrhage (peptic esophagitis) but SU was maintained for 3 additional months untill disease progression. In 1 pt (RCC), LMWH and SU were maintained for up to 24 months. Conclusions: The incidence of symptomatic PE among pts treated with SU was within the expected range for cancer patients receiving chemotherapy, but PE occurred early after SU initiation. Concomitant SU and LMWH treatment is feasible but might expose to severe hemorrhage. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology Pfizer Oncology