Mixed News on Tough-to-Treat Lung Cancer

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 cancer.

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 Cancer.

“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 months.

“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 they do.”

The next step will be larger trials involving cancer patients, Bunn

“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 adenocarcinomas.

“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.

More information

The U.S. National Cancer Institute has more on lung

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