In February 2015, the FDA approved the molecularly
targeted therapeutic palbociclib (Ibrance) for use in
combination with letrozole for treating postmenopausal
women with estrogen receptor–positive, HER- 2–negative,
advanced breast cancer.
Palbociclib is the first in a new class of agents that block cell
multiplication by inhibiting the function of two proteins
that play a role in driving this natural process—
cyclin-dependent kinase 4 (CDK4) and CDK6 (see Figure 16, p.
78). Its FDA approval was based on early-stage clinical
trial results showing that adding palbociclib to letrozole
significantly increased the time to disease progression
among postmenopausal women with estrogen receptor–
positive, HER- 2–negative, advanced breast cancer ( 108),
and it is hoped that longer follow-up of these patients,
as well as an additional large-scale study that is already
underway, will show that this combination of therapeutics
also extends survival.
With recent early results from a phase III clinical trial
showing that adding palbociclib to another estrogen
receptor–targeted therapeutic, fulvestrant, also increases
the time to disease progression among postmenopausal
women with hormone receptor–positive, HER- 2–negative,
advanced breast cancer ( 109), there will undoubtedly be
many more women like Janet Klein (see p. 76) who will
benefit from palbociclib in the future.
Thwarting the Most Common Form of Skin Cancer
Basal cell carcinoma is the most commonly diagnosed
cancer among people of European ancestry ( 110, 111).
Most patients are cured with topical therapy, surgery,
radiotherapy, or a combination of these treatments.
However, in a small fraction of patients, the disease
progresses and becomes extremely challenging to treat.
The discovery two decades ago that genetic mutations
leading to overactivation of a signaling pathway, called
the Hedgehog pathway, fuel the growth of nearly all basal
cell carcinomas led researchers to develop therapeutics
that target the Hedgehog pathway ( 110). The first of these
molecularly targeted therapeutics, vismodegib (Erivedge),
was approved by the FDA for the treatment of locally
advanced or metastatic basal cell carcinoma in January
2012 ( 84).
A July 2015 decision by the FDA to approve a new
Blocking the Blood Supply to Tumors
Hedgehog pathway–targeted therapeutic called sonidegib
(Odomzo) provides a new treatment option for patients
with locally advanced basal cell carcinoma that has recurred
following surgery or radiotherapy. The decision was based
on early results from an ongoing clinical trial showing that
more than half of the patients who received sonidegib have
had their tumors shrink dramatically ( 112). It is hoped
that with more time, sonidegib will also prove to increase
survival for patients with this devastating disease.
Research has shown that many solid tumors need to
establish their own blood and lymphatic vessel network
to grow and survive. It has also led to the identification of
many molecules that control the growth of the new blood
and lymphatic vessels within a tumor. This combined
knowledge has guided the development of 11 anticancer
therapeutics that specifically block these many molecules
(see Figure 17, see p. 79). These therapeutics are sometimes
referred to as antiangiogenic agents.
Bevacizumab (Avastin) was the first of this growing class
of anticancer therapeutics; it was approved by the FDA for
the treatment of metastatic colorectal cancer in 2004. Since
then, bevacizumab has been approved for the treatment of
a variety of other types of cancer, with the most recent suite
of approvals coming 10 years after the first (see Appendix
Table 1, p. 10). Specifically, the use of bevacizumab in
combination with certain traditional chemotherapeutics
was approved for the treatment of persistent, recurrent,
or metastatic cervical cancer in August 2014, and for the
treatment of platinum-resistant recurrent epithelial ovarian,
fallopian tube, or primary peritoneal cancer in November
2014. The fact that adding bevacizumab to treatment with
traditional chemotherapeutics provided clinical benefit
in phase III clinical trials ( 113, 114), offers new hope for
patients with these diseases.
The newest member of the class is lenvatinib (Lenvima).
In February 2015, lenvatinib was approved by the FDA
for treating certain patients with thyroid cancer—those
with locally recurrent or metastatic differentiated thyroid
cancer that has progressed despite radioactive iodine
therapy. Differentiated thyroid cancers will account for
about 56,205 thyroid cancers newly diagnosed in the
United States in 2015. Although many patients with this
type of cancer are treated successfully, the 10-year survival
rate for those with disease that is refractory to radioactive
iodine therapy is just 10 percent from when metastases
are detected ( 115). With results of a phase III clinical trial
showing that lenvatinib was effective for almost 65 percent
of patients ( 115), this molecularly targeted therapeutic
will undoubtedly transform the lives of many patients with
metastatic differentiated thyroid cancer, like Lori Cuffari
(see p. 80), in the future.
The FDA recently also approved two new uses for another
antiangiogenic agent, ramucirumab (Cyramza). In
December 2014, it was approved for some patients with
the most deadly form of lung cancer, NSCLC, after it was