Lung Cancer Drugs:

Lung cancer is cancer that begins in
the lungs, the two organs found in the
chest that help you breathe.

The lungs are made up of areas called
lobes. The right lung has three lobes;
the left lung has two, so there's room
for the heart. When you breathe, air
goes through your nose, down your
windpipe (trachea), and into the lungs
where it spreads through tubes called
bronchi. Most lung cancer begins in
the cells that line these tubes.

There are two main types of lung
cancer:

Non-small cell lung cancer (NSCLC) is
the most common type of lung cancer.
Small cell lung cancer makes up about
20% of all lung cancer cases.


FDA APPROVES XALKORI
(CRIZOTINIB) FOR A TYPE OF LATE
STAGE LUNG CANCER
In August 2011 the FDA approved
Xalkori  (crizotinib) to treat certain
patients with late-stage (locally
advanced or metastatic), non-small cell
lung cancers (NSCLC) who express
the abnormal anaplastic lymphoma
kinase (ALK) gene.

Xalkori is being approved with a
companion diagnostic test that will help
determine if a patient has the
abnormal ALK gene, a first-of-a-kind
genetic test called the Vysis ALK Break
Apart FISH Probe Kit. It is the second
such targeted therapy approved by the
FDA this year.

This ALK gene abnormality causes
cancer development and growth.
About 1 percent to 7 percent of those
with NSCLC have the ALK gene
abnormality. Patients with this form of
lung cancer are typically non-smokers.
Xalkori works by blocking certain
proteins called kinases, including the
protein produced by the abnormal ALK
gene.

Xalkori is a pill taken twice a day as a
single-agent treatment.

Xalkori’s safety and effectiveness were
established in two multi-center, single-
arm studies enrolling a total of 255
patients with late-stage ALK-positive
NSCLC. A sample of a patient’s lung
cancer tissue was collected and tested
for the ALK gene abnormality prior to
study enrollment. Most patients in the
studies had received prior
chemotherapy.

In one study, the objective response
rate was 50 percent with a median
response duration of 42 weeks. In
another, the objective response rate
was 61 percent with a median
response duration of 48 weeks.

This new drug does offer promise for
roughly 4% of people who develop
lung cancer. And 4% isn't a tiny
number considering lung cancer is the
leading cause of cancer deaths for
both men and women in the United
States.
The medication crizotinib was studied
on patients with stage 4 non-small cell
lung cancer with a particular gene
mutation. In these people (who make
up 4% of lung cancer patients) the
gene ALK fuses with another gene
called EML4, resulting in the
production of a protein that stimulates
the growth of cancers. Crizotinib works
by blocking this protein.

In patients treated with crizotinib, 57%
were found to have a reduction in their
tumors and 87% had stabilization of
their disease after 8 weeks.
This response rate is unprecedented
in lung cancer. The patients taking
part in this clinical trial had already
failed on at least 2 previous
chemotherapies, and their chances of
responding to a third chemotherapy
would be at best 10%.
This work adds another biomarker to
the field of lung cancer.




ROCHE'S METMAB
Roche's Metmab, an antibody
targeting the MET receptor. This
phase II evaluated the antibody in
combination with Tarceva in lung
cancer patients.

Roche's Metmab,  when combined with
Tarceva,  led to a dramatic effect in
patients who overexpressed MET on
their tumors.

The drug appeared deleterious in MET
negative patients.

Met is a  protein or receptor
associated with a poor outcome in
many cancers.

Although the number of patients is
relatively small, the overall survival
benefit was astounding (12.6 vs. 4.6
months). This trial will surely lead to a
phase III study in MET positive lung
cancer in the coming future.

Given the spectacular results, Metmab
has become a real threat to Arqule's
ARQ197, a small molecule MET
inhibitor that also generated a positive
signal in combination with Tarceva in
lung cancer. It is very hard to compare
the two drugs due to patient selection
and stratification issues (discussed
here). Arqule is currently evaluating
patients in its phase II trial
retrospectively using the same criteria
used for Metmab, so it would be very
interesting to see whether  a similar
trend is observed.


LILLY'S ALIMTA FOR NON-SMALL
CELL LUNG CANCER
Lilly's  Alimta has been able to capture
market share in non-small cell lung
cancer (NSCLC) thanks to impressive
activity as second line or maintenance
therapy in a large subset (70%) of
patients.  

This year (in  2011), investigators will
present results from a phase III trial
which evaluated Alimta given both as
first line and maintenance therapy.
Although the drug is approved for both
treatment lines separately, positive
results could help Lilly drive sales even
higher and increase the average
number of cycles patients receive.


THE DRUG REOLYSIN TESTED FOR
MULTIPLE CANCERS
Oncolytics has concluded 12 human
clinical trials with Reolysin.  Besides
head and neck cancer, Reolysin is
being studied in multiple early- and
mid-stage settings by the NCI and by
Oncolytics in a variety of advanced
malignancies.

Phase  2 Reolysin trials on schedule to
report data in 2010-11, including  a 36-
patient lung cancer trial.
The  Phase 2 lung cancer data,
expected later this year, is of particular
importance as it may be a trigger for a
partnership with Big Pharma.

Experts have hailed the new drug,
made from a harmless bug that can
cause stomach upsets, as a major new
weapon in the battle to find a cure for
cancer.
Early evidence from a trial carried out
in patients with advanced, untreatable
cancers who had stopped benefiting
from radiotherapy has seen
remarkable results.
The simple injection has stopped the
spreading of the deadly disease in its
tracks and has even successfully
reversed its growth.
In one remarkable case, a man who
had a large tumor mass saw it shrink
enough to be surgically removed.
Another patient with the most deadly
form of skin cancer which had spread
was still alive 17 months after
treatment started.



TARCEVA IS EFFECTIVE FOR LUNG
CANCER WITH CERTAIN MUTATIONS
Already, there is a body of evidence
showing that lung cancer with tumors
that harbor a mutation of the epidermal
growth-factor receptor (EGFR) benefit
from the EGFR inhibitor erlotinib (with
about a 70% response rate). This drug
has become a first-line therapy and is
used alone in this patient subgroup.
Now there is another subgroup and
another targeted agent.
EGRF mutations are found in about
10% of patients with NSCLC, and ALK
gene rearrangements in about 3% to
5% of these patients.But these 2
biomarkers are mutually exclusive.
Tarceva is  marketed in the United
States by Genentech and OSI
Pharmaceuticals and elsewhere by
Roche.

Lung cancer patients given drugs such
as Tarceva and Nexavar fare better
when personalized: their tumors are
first tested for certain genetic traits
and then matched with the
corresponding treatment, a study
found at the University of Texas M.D.
Anderson Cancer Center in Houston.


OTHER DEVELOPMENTS
Motesanib for Non-Small Cell Lung
Cancer made by Amgen, Takeda and
Millennium in  trial Phase 3;