TUESDAY, Jan. 10 (HealthDay News) -- Dutch researchers report
disappointing results from an early clinical trial of the drug
Nexavar (sorafenib) in fighting a tough-to-treat form of lung
But, in better news, an experimental drug known as ganetespib
showed promise in laboratory and animal experiments.
The results of both studies were to be presented Tuesday at an
American Association for Cancer Research/International Association
for the Study of Lung Cancer meeting in San Diego.
In recent years, researchers have made some headway in finding
treatments to combat lung cancer, which often doesn't respond well
to chemotherapy, explained Dr. Len Lichtenfeld, deputy chief
medical officer of the American Cancer Society.
Those treatments include drugs such as crizotinib (Xalkori) and
erlotinib (Tarceva), which are most effective in tumors that
contain certain genetic mutations.
However, those drugs tend to not work well in people with tumors
that contain a particular type of mutation in the KRAS gene. KRAS
is the most common molecular mutation, present in about 25 percent
of people with non-small cell lung cancers such as adenocarcinoma,
particularly smokers, said Dr. Paul Bunn, a professor of lung
cancer research at the University of Colorado and executive
director of the International Association for the Study of Lung
"The patients who have this mutation have a somewhat worse prognosis than patients who don't have this mutation, and have worse outcomes with chemotherapy," Bunn said. "Most drugs produce a shrinkage of the tumor in less than 10 percent of KRAS patients."
While a smaller, even earlier trial showed sorafenib might be
that drug, the latest findings were not impressive. This larger
trial by researchers in the Netherlands involving 57 patients with
non-small cell lung cancer who had already failed chemotherapy and
who had the KRAS mutation showed the median progression-free
survival was just 2.3 months. Overall survival was about five
"They were undoubtedly hoping that progression-free survival would be longer, maybe four or five months, and overall survival would be six or eight months," Bunn said. "The results were not encouraging. Their basic conclusion is that we should find something better for these patients, and not spend a lot of time on a big randomized trial to show it has a teeny effect or no effect."
In addition, sorafenib was not compared to other drugs, or even
to no treatment, Lichtenfeld said, so there is no way of gauging if
the 2.3 months represents a true benefit above and beyond what
patients would experience otherwise.
A second study done on non-small cell cancer cells and mice with
the KRAS mutation showed more promise, experts said.
In it, researchers tested the drug ganetespib, which inhibits
the Hsp90 protein. When combined with other cancer drugs,
ganetespib seems to affect multiple other proteins present in the
cancer cell that help the cancer cell thrive, Lichtenfeld said.
"The presence of this protein [Hsp90] really directs or impacts many proteins within the cancer cell that are necessary for it to survive," Lichtenfeld said. "If you can block that protein's effect, you then have other proteins that are blocked, and by blocking them you could shut down the cancer cell and severely impact the cell and its growth patterns. That is interesting and exciting from a laboratory point of view."
However, Lichtenfeld noted, "the problem we always face is
translating what we see in the laboratory to clinical medicine.
There are so many times we have promising and exciting findings in
the laboratory that don't translate into patients, but occasionally
The next step will be larger trials involving cancer patients,
"I would say this other approach is more promising than the sorafenib, and certainly worthy of additional studies, but not ready for clinical primetime," Bunn said.
Non-small cell lung cancer is the most common type of lung
cancer. Non-small cell cancers include squamous cell and
"The big picture is we are learning about these mutations that tell us something about lung cancer, which has in some cases given us targets to guide us to use certain drugs because we know they have a higher chance of being effective," Lichtenfeld said.
Lung cancer is the leading cause of cancer deaths in the United
States for men and women, killing an estimated 157,000 people this
year, according to the American Cancer Society.
Experts note that research presented at meetings has not been
subjected to the same type of rigorous scrutiny given to research
published in peer-reviewed medical journals.
U.S. National Cancer Institute has more on lung
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