Sorafenib improves survival by 39% in advanced renal cell carcinoma

Overall survival was 19.3 months for patients on sorafenib and 14.3 months for placebo.

Issue: December 1, 2006

Treating renal cell carcinoma with sorafenib improved survival and quality of life, according to phase-3 trial data from the TARGETs study presented at ASCO 2006.

Tim Eisen, PhD, FRCP, consultant medical oncologist at The Royal Marsden Hospital in London, presented interim data from a double blind, placebo-controlled phase-3 trial. The TARGETs study demonstrated a 39% improvement in survival in patients treated with sorafenib (Nexavar; Bayer, Onyx), compared with placebo (P=.018, HR=0.72).

Researchers then unblinded the study and gave patients who were receiving placebo the opportunity to switch treatment to sorafenib, based on the clinical and statistical significance of a definitive analysis of progression-free survival. Eisen reported the interim overall survival results of the crossover.

Crossing over

Originally, researchers randomized more than 900 patients with advanced RCC to receive either 400 mg sorafenib (n=451) or placebo (n=452) twice a day. Each of the patients had previously failed one prior systemic therapy. The primary endpoint of the study was overall survival. Researchers also assessed progression-free survival, overall response rate, quality of life and safety.

In April 2005, the researchers unblinded the trial and more than 200 patients switched from placebo to sorafenib treatment. They based overall survival results on an analysis of 367 patient deaths that had occurred by November 30, 2005.

The updated data showed continued improvement in the median overall survival of 19.3 months for sorafenib, compared with 15.9 months for placebo (95% CI, 0.63-0.95, HR=0.77) despite the fact that 48% of placebo patients crossed over to sorafenib. Eisen also reported overall survival after censoring data from the placebo patients to examine the effect of crossover. Median overall survival was 19.3 months for sorafenib vs. 14.3 months for placebo (95% CI, 0.58-0.93, HR=0.74).

Although these data did not reach the trial endpoint, they suggest a favorable survival trend for patients who received sorafenib. Researchers will make their final analysis of overall survival when they observe 540 deaths.

“Consistent with the original interim analysis, patients receiving Nexavar lived longer than patients receiving placebo, despite almost 50% of placebo patients crossing over to Nexavar,” Eisen said in a prepared statement. “These data are encouraging and should be considered preliminary pending the final analysis.”

FDA Drug Approvals in 2006

Drug Name	Indication
anidulafungin (Eraxis, Pfizer)	candidemia, peritonitis, intra-abdominal abscesses, esophageal candidiasis
aprepitant (Emend, Merck)	chemotherapy-induced nausea and vomiting
bevacizumab (Avastin, Genentech)	metastatic colorectal cancer
bevacizumab (Avastin, Genentech)/carboplatin/paclitaxel	unresectable, locally-advanced, recurrent or metastatic non-squamous, non–small cell lung cancer
cetuximab (Erbitux; ImClone Systems, Bristol-Myers Squibb)	unresectable squamous cell carcinoma of the head and neck
darbepoetin alfa (Aranesp, Amgen)	chemotherapy-induced anemia
dasatinib (Sprycel, Bristol-Myers Squibb)	chronic myeloid leukemia
decitabine (Dacogen, MGI Pharma)	myelodysplastic syndrome
docetaxel (Taxotere, Sanofi Aventis)	inoperable locally-advanced squamous cell carcinoma of the head and neck
gemcitabine (Gemzar, Eli Lilly)	recurrent ovarian cancer
HPV vaccine (Gardasil, Merck)	prevention of cervical cancer
panitumumab (Vectibix, Amgen)	metastatic colorectal cancer
pegaspargase (Oncaspar, Enzon)	acute lymphoblastic leukemia
posaconazole oral suspension (Noxafil, Schering)	invasive Aspergillus and Candida infections in immunocompromised patients
rituximab (Rituxan; Genentech, Biogen)/CVP	follicular non-Hodgkin’s lymphomalow-grade NHL in patients with stable disease
rituximab (Rituxan; Genentech, Biogen)/CHOP	diffuse large B-cell, CD20-positive NHL
sorafenib (Nexavar; Bayer, Onyx)	advanced renal cell carcinoma
topotecan (Hycamtin, GlaxoSmithKline)/cisplatin	late-stage cervical cancer
vorinostat (Zolinza; Merck, Pantheon)	cutaneous T-cell lymphoma

Quality of life

Rahul Dhanda, PhD, presented an evaluation of health-related quality of life and symptoms observed in the phase-3 trial.

Researchers measured quality of life and symptoms of treatment at baseline, at the beginning of each of the five cycles of treatment and at the end of treatment. Researchers saw a clinical benefit among the patients taking sorafenib, compared with those taking placebo.

They found no differences in physical, emotional, social or functional well-being between patients treated with sorafenib and those treated with placebo. They also found that, compared with those taking placebo, the overall quality of life in patients treated with sorafenib was not adversely impacted.

The drug also had a positive effect on symptoms such as cough (P<.001), fevers (P<.002), shortness of breath (P<.031), concern over a worsening condition (P<.001), and the ability to enjoy life (P<.012). The only symptom that was lower among placebo patients was concern about treating adverse events (P<.001).

For more information:

Eisen T, Bukowski RM, Staehler M, et al. Randomized phase III trial of sorafenib in advanced renal cell carcinoma: Impact of crossover on survival. Abstract 4524.

Dhanda R, Gondek K, Song J, et al. A comparison of quality of life and symptoms in kidney cancer patients receiving sorafenib versus placebo. Abstract 4534.

Both presented at: 2006 ASCO Annual Meeting; June 2-6; Atlanta.