ASCO 2011 Update June 5

This morning’s program included over 25 different research presentations on kidney cancer. To summarize just a few:

Pazopanib (Votrient) studies:
– the incidence of clinically relevant hypothyroidism in patients with advanced rcc receiving pazopanib is low compared to other anti-angiogenic TKIs. May explain lower levels of fatigue.

– liver toxicity with pazopanib  (elevated ALT 10.9%  and AST 7.4%). While over 50% of patients had elevated liver function tests, only 2% or less needed to stop treatment because of it. Dosage may need to be adjusted per guidelines.

– phase 2 trial of 46 patients using pazopanib 2nd line post Sutent or Afinitor reported an ORR (overall response rate) of 22% and a PFS (Progression Free Survival) of 9 months. 

Sunitinib (Sutent) studies

– After treatment discontinuation, tumour growth resumes the same growth rate as before the treatment. (No acceleration of growth was noted.)

– Small study of mrcc with brain mets showed no safety issues but limited efficacy.

-Sutent efficacy in elderly patients comparable (>70 years old). Side effect profile was similar but certain side effects were more prevalent such as fatigue, cough and edema (e.g., leg swelling). Net: age should not dictate the treatment or dose level to be used.

Afinitor (everolimus) studies

– combination of Afinitor + Nexavar needed 50% reduced dosage of both drugs due to toxicity, but not more effective than either drug on its own.

– international expanded access program (including Canada) for Afinitor showed over 50% of patients achieved stable disease.

Nexavar (sorafenib) studies

– Swedish study using national registry data indicates that treatment duration is similar for both Sutent and Nexavar and interestingly noted that Nexavar was favourable as a 1st line treatment choice.

– UK dose escalation study indicated that doses beyond 400mg twice a day were not well tolerated. Study showed a median PFS of 7.4 months for first-line treatment.

Other interesting studies
– Sutent study with patients on dialysis or with impaired renal function. Efficacy and toxicity generally unchanged. Safer to start at lower dose and increase.

– History of smoking: overall survival and cancer-specific survival are higher for non-smokers. A history of smoking was associated with worse clinical and pathological features and higher risk of a mutation in the p53 gene. In non-metastatic rcc, the more a patient smokes, the worse the survival outcome.

— for patients with prior heart disease: hypertension, heart failure and ejection fraction changes are all well documented with VEGF inhibitors. Patients with cardiac conditions may be safer with mTOR inhibitors.

— for rarer subtypes of rcc (non clear cell), discussion that VEGF inhibitors show some activity, but not as much as with clear cell. Different treatment paths for papillary type 1 and 2 based upon different gene profiles (cMET vs FH).

Summary by Dr. Eric Jonasch from MD Anderson Cancer Center:  “Serial application of available therapy is the accepted therapeutic strategy in 2011.”

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