80 AACR CANCER PROGRESS REPORT 2017
was granted accelerated approval for treating both patients
with locally advanced or metastatic urothelial carcinoma
that has progressed despite treatment with a platinum-containing cytotoxic chemotherapeutic and those for
whom a platinum-containing cytotoxic chemotherapeutic
is not an option.
In addition, in March 2017, pembrolizumab was granted
accelerated approval for treating patients with classical
Hodgkin lymphoma that has not responded to treatment
or that has relapsed after three or more different treatments.
The approval was based on results from a phase II clinical
trial showing that pembrolizumab treatment led to tumor
shrinkage in the majority of patients (176).
The number of uses for which atezolizumab is an FDA-approved treatment option was also expanded during
the 12 months covered by this report. In October 2016,
it was approved by the FDA for treating patients with
metastatic NSCLC that has progressed despite treatment
with a platinum-based cytotoxic chemotherapeutic or an
appropriate molecularly targeted therapeutic. The approval
was based on results from a phase III clinical trial that
showed that atezolizumab improved survival compared
with the cytotoxic chemotherapeutic docetaxel, which is
standard of care for patients with metastatic NSCLC that
has progressed during or after initial chemotherapy (177).
The successes highlighted here have led to clinical trials
in which PD-1/PD-L1–targeted checkpoint inhibitors are
being tested as a potential treatment for numerous other
types of cancer. Results are not available yet for most of these
trials. However, initial data show that pembrolizumab may
benefit some patients with gastric cancer and mesothelioma
(178, 179) and that nivolumab may benefit some patients
with liver cancer (180).
Despite the rapid expansion in the number of FDA-
approved checkpoint inhibitors and the number of FDA-
approved uses for these revolutionary immunotherapeutics,
it is important to note that several of the approvals were
granted through the FDA accelerated approval program
(see sidebar on Accelerated Approval, p. 63). As such,
additional clinical testing is ongoing to confirm that the
checkpoint inhibitors do indeed provide clinical benefit
for patients as anticipated.
Additional clinical trials and longer follow-up of patients
in the initial clinical trials are vital for deepening our
understanding of the benefits and potential harms
of checkpoint inhibitors. They may also lead to the
identification of biomarkers that identify the patients
most likely to benefit from a given treatment. This is
important because it could allow a patient unlikely to
benefit from a particular checkpoint inhibitor to be spared
the potential toxicity of the treatment and to immediately
start an alternative treatment, saving patients precious
time in their race to find an effective therapy.
Currently, the only biomarkers used in the clinic for
identifying which patients are most likely to benefit from
a given PD-1/PD-L1 checkpoint inhibitor are the presence
of PD-L1 in a tumor and the presence of microsatellite
instability–high or DNA mismatch–repair deficiency in
a solid tumor (see Figure 17, p. 76). These biomarkers are
used for identifying those patients with lung cancer and
those with solid tumors, respectively, who are most likely
to benefit from pembrolizumab. In some other cases—
for example, the use of durvalumab as a treatment for
bladder cancer and the use of nivolumab as a treatment
for lung cancer—the presence of high tumor levels of PD-
L1 has been linked to a greater chance of benefit from
a PD-1/PD-L1 checkpoint inhibitor. However, some
patients whose tumors lack PD-L1 also benefited from
these treatments. Thus, it is clear that new biomarkers are
needed for identifying patients most likely to benefit from
treatment with a checkpoint inhibitor, and this is an area
of intensive research investigation (181).
Supporting Cancer Patients and Survivors
Research is driving advances in cancer detection, diagnosis,
and treatment that are helping more and more people to
survive longer and lead fuller lives after a cancer diagnosis.
According to the latest estimates, more than 15. 5 million
U.S. adults and children with a history of cancer were
alive on January 1, 2016, compared with just 3 million in
1971, and this number is projected to rise to 20. 3 million
by January 1, 2026 (182, 183).
Each of these people has a unique experience and outlook,
which can range from successful treatment and living
cancer free for the remainder of his or her life to living
continuously with cancer for the remainder of life.
Therefore, not all people who receive a cancer diagnosis
identify with the frequently used term “cancer survivor.”
Cancer survivorship encompasses three distinct phases:
the time from diagnosis to the end of initial treatment,
the transition from treatment to extended survival, and
Urothelial carcinoma is
the most common type
of bladder cancer, which
is expected to be the
sixth most commonly
diagnosed cancer in the
United States in 2017 ( 2).
continued from p. 77