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SOLTI-0701, a randomized Phase IIb trial evaluating the efficacy and safety of sorafenib in combination with

capecitabine for the treatment of patients with locally advanced or metastatic breast cancer

Presented by Dr. Jose BaselgaAuthors: Sunil Verma

Date posted: September 28th, 2009

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R

Control arm:

Capecitabine 1000mg/m2 bid (d1-14) + Placebo

Experimental arm:

Capecitabine 1,000 mg/m2 bid + Sorafenib 400mg po bid

N=229MBC

1st or 2nd lineHer 2 normal

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RESULTS

Cape +

Placebo

Cape +

Sorafenibp-value

PFS/TTP (median,

mos) 4.1 6.4 P=0.0006

OS

(median, mos)

Not mature – data will be available in 2010

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STUDY COMMENTARY

• Sorafenib is an oral multi-kinase inhibitor with anti-angiogenic and anti-tumor activity. It has documented activity and use in Hepatocellular and Renal Cell Cancer

• This is a large well conducted randomized phase IIb placebo-controlled clinical trial

•Efficacy results show a marked improvement in PFS which is particularly impressive for patients receivng this combination in first line MBC setting (7.6 m vs 4.1m)

• Toxicity was concerning especially for Hand Foot Syndrome in combination arm where 45% of patients had grade3/4 HFS.

• OS data in not yet mature and is expected in 2010

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BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS

• RIBBON-1 Trial was the first trial that showed that capecitabine + anti-angiogenic agent (Bevacizumab) improves outcomes in MBC

• This study confirms that anti-angiogenic approach in combination with capecitabine is effective even when combined with an oral multi-kinase inhibitor i.e. sorafenib

• This is the second trial that shows that small molecules when combined with chemotherapy are efficacious. The previous trial evaluated lapatinib in combination with capecitabine for her2 positive patients

• While there is significant improvement in PFS in this trial, there is considerable Grade ¾ HFS toxicity with this combination

• It is exciting to have a new player in MBC in sorafenib, but more work needs to be done to evaluate predictive biomarkers, use with ideal chemo/targeted partners and addressing toxicity with this agent.