(RxWiki News) The newer generations of cancer treatment focus on highly specific molecular interactions, sometimes even specific genetic mutations. And despite the biological advancements, they may not work for everyone.
It's always good to have options. Researchers from several different universities from across Europe collaborated and recently finished phase II testing of tivantinib in a group of patients who haven't responded to other treatments for liver cancer -- hepatocellular carcinoma (HCC).
"Ask your oncologist about drug trials."
Their analysis showed that the drug, one of several c-met (a cellular protein involved in cancer growth) inhibitors still in testing, nearly doubled the overall survival time from 3.8 months in the placebo group to 7.2 months in the treatment group.
Time to disease progression showed a similar effect, from 1.5 months to 2.9 months.
Researchers also concluded that the frequency and type of side effects were acceptable, but said they will adjust the phase III trial to have a lower average dose.
As the completed phase II trial evaluates toxicity and dosage, no hard data on how well the drug works was available. The next phase of the drug trial -- phase III testing -- will directly compare tivantinib against the current gold standard treatment.
Results from all three phases documenting safety, side effects, and effectiveness of the drug will be used in an evaluation for formal approval by the U.S. Food and Drug Association.
Tivantinib targets a protein called c-Met, which is normally involved in the growth of healthy liver cells, but commonly becomes deranged during cancer progression.
"These findings are the first randomized data in HCC showing an overall survival advantage with a MET inhibitor administered as a single agent and are the first identification of a biologic subgroup of patients responding to a targeted therapy,” said Lorenza Rimassa, MD, deputy director of oncology at the Humanitas Cancer Center in Milan and the study's first author.
“The data suggest that patients significantly benefited in time to progression and, importantly, those in a biologically relevant MET-high subgroup had an additional significant advantage in overall survival,” Dr. Rimassa added.
Not everyone was enthusiastic about the drug, however. One doctor interviewed at the conference said the conclusions could be premature.
Jordan Berlin, MD, of the Vanderbilt-Ingram Cancer Center, referenced the problems with earlier studies on drugs for pancreatic cancer when he said that small studies such as this phase II trial can be misleading at times.
“We have been fooled by subset analyses…[before]. They are hypothesis driving, not trial driving,” Dr. Berlin said.
The study followed 107 patients with liver cancer during a treatment program using tivantinib.
Patients were evaluated every six weeks, with continual use of tivantinib until either the cancer stopped responding to the treatment or toxic side effects were documented.
All patients in the trial had not responded to prior treatments, and none of the patients in the study were candidates for surgery.
Side effects included low appetite, anemia and weakness in a quarter of patients. The most serious side effect documented was immune suppression, with sepsis due to bacterial infection occurring in five patients.
Studies presented at conferences should be considered preliminary until published in a peer-reviewed journal.
Researchers disclosed financial relationships with ArQule and Daiichi Sankyo, which are both involved in the research and manufacturing of the drug.