AMERICAN ASSOCIATION FOR CANCER RESEARCH 61
set the stage for the new era of precision medicine, an era
in which the standard of care for many patients is changing
from a one-size-fits-all approach to one in which greater
understanding of the patient and his or her tumor dictates
the best treatment option for the patient.
Therapeutics directed to the molecules involved in different
aspects of the cancer process target the cells within a
tumor more precisely than cytotoxic chemotherapeutics,
thereby limiting damage to healthy tissues. The greater
precision of these molecularly targeted therapeutics tends
to make them more effective and less toxic than cytotoxic
chemotherapeutics. As a result, they are not only saving the
lives of countless patients with cancer, but also allowing
these individuals to have a higher quality of life than many
who came before them.
In the 12 months spanning August 1, 2016, to July 31,
2017, the FDA approved seven new molecularly targeted
anticancer therapeutics (see Table 1, p. 10). During this
period, they also approved new uses for four previously
approved molecularly targeted anticancer therapeutics,
dabrafenib ( Tafinlar), ibrutinib (Imbruvica), regorafenib
(Stivarga), and trametinib (Mekinist).
Ibrutinib targets a protein called BTK, which is a
component of a signaling pathway that promotes the
survival and expansion of immune cells called B cells. In
January 2017, the FDA granted accelerated approval to
ibrutinib for treating certain patients with a type of non-Hodgkin lymphoma called marginal zone lymphoma,
which arises in a certain population of B cells (see sidebar
on Accelerated Approval, p. 63). The approval was based on
results from a phase II clinical trial showing that ibrutinib
caused significant tumor shrinkage in about 50 percent of
patients whose disease had progressed despite standard-of-care treatment (129). This followed approvals in 2013,
2014, and 2015 for chronic lymphocytic leukemia and
two other forms of non-Hodgkin lymphoma—mantle cell
lymphoma and Waldenström macroglobulinemia—all
of which also arise in B cells. These prior approvals were
highlighted in earlier editions of the AACR Cancer Progress
Report ( 1, 25).
Regorafenib targets proteins that promote the growth of
new blood and lymphatic vessels, which tumors need to
grow and survive. In April 2017, the FDA expanded the use
of regorafenib to include the treatment of certain patients
with the most common form of liver cancer, hepatocellular
carcinoma, after it was shown in a phase III clinical trial to
improve survival for patients with hepatocellular carcinoma
that had progressed despite standard-of-care treatment with
sorafenib (Nexavar) compared with placebo (130). The new
approval followed approvals in 2012 and 2013 for colorectal
cancer and gastrointestinal stromal tumors, which were
highlighted in the AACR Cancer Progress Report 2013 ( 33).
The following discussion focuses on the other FDA
approvals for molecularly targeted anticancer therapeutics
that occurred in the 12 months covered by this report.
Adding Precision to Treatment
for Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is the most common type
of leukemia diagnosed in the United States, with more
than 21,000 new cases anticipated in 2017 ( 2). It is also the
type of leukemia with the lowest overall five-year relative
survival rate, 27 percent ( 5).
Treatment has changed little in the past few decades (131).
It usually occurs in two phases. The first, which is known
as the induction phase, includes an intensive course of
cytotoxic chemotherapy designed to put the leukemia into
remission. The second phase is known as the consolidation
phase. It includes further cytotoxic chemotherapy or a
stem cell transplant and it is designed to keep the leukemia
in remission.
In recent years, research has substantially increased our
understanding of the biology of AML, in particular the
genetic mutations that fuel leukemia growth (132). One
of the genes most frequently mutated in AML is FLT3,
and patients with this form of AML have particularly poor
outcomes (133).
This knowledge ultimately led to the first new FDA-
approved treatment for AML in almost three decades,
midostaurin (Rydapt). Midostaurin is also the first
molecularly targeted therapeutic approved for treating
AML. It targets several related molecules called tyrosine
kinase receptors, including FLT3 and KIT, and it was
approved by the FDA in April 2017 for treating adults ne wly
diagnosed with AML harboring a mutation in the FLT3
Regorafenib (Stivarga) is the
first
new anticancer therapeutic
approved for treating advanced
hepatocellular carcinoma
in a decade.
continued from p. 57
