with advanced renal cell carcinoma that has progressed
despite treatment with at least one antiangiogenic
therapeutic after it was shown to improve overall survival
for patients enrolled in a phase III clinical trial compared
with everolimus, a recommended treatment in this situation
(158) (see Blocking the Blood Supply to Tumors, p. 80).
The approval for Hodgkin lymphoma came in May 2016,
after results from early-stage clinical trials showed that
it caused partial or complete shrinkage of tumors in the
majority of patients with classical Hodgkin lymphoma
that had relapsed or progressed despite treatment with an
autologous hematopoietic stem cell transplant and post-transplantation brentuximab vedotin (Adcetris) (159).
The fourth immunotherapeutic to be approved by the FDA
that works by releasing brakes on the immune system is
atezolizumab (Tecentriq). Atezolizumab targets PD-L1,
preventing it from attaching to PD- 1 and triggering its
brake function. It also prevents PD-L1 from attaching to
and triggering another brake on T cells called B7.1 (160).
In May 2016, atezolizumab was approved for treating
patients with locally advanced or metastatic urothelial
carcinoma that has progressed despite treatment with a
platinum-based cytotoxic chemotherapeutic. The decision
was based on the fact that atezolizumab treatment led to
partial shrinkage or complete disappearance of tumors
for patients enrolled in a phase II clinical trial (161). This
approval provides tremendous hope for patients with
urothelial carcinoma because atezolizumab is the first
new treatment shown to improve outcomes for patients,
like Dave Maddison (see p. 88), in 30 years.
The spectacular successes highlighted here have
motivated researchers to begin testing these revolutionary
immunotherapeutics as a potential treatment for numerous
other types of cancer. Results are not yet available for
most of these clinical trials. However, initial results show
that nivolumab and pembrolizumab may benefit some
patients with head and neck cancer (162, 163), and that
pembrolizumab may benefit a subgroup of patients with
colorectal cancer (164).
Despite the tremendous achievements, treatment with FDA-approved immunotherapeutics that work by releasing brakes
on the immune system does not yield remarkable and long-term responses for all patients. As a result, researchers are
testing various ways to help increase the number of patients
who may benefit from these immunotherapeutics, including
evaluating how well they work in combination. The FDA
approved the first of these combinations, ipilimumab and
nivolumab, in September 2015, after it was shown in a phase II
clinical trial that adding nivolumab to ipilimumab increased
the percentage of patients with metastatic melanoma to have
tumor shrinkage or disappearance more than five-fold (165).
The concept of combining members of this burgeoning
class of immunotherapeutics with immunotherapeutics
that work in different ways, as well as other types of
anticancer treatments, including radiotherapy, cytotoxic
chemotherapeutics, and molecularly targeted therapeutics,
is also being tested in clinical trials for a wide array of
types of cancer.
Hodgkin
lymphoma
is a rare type of cancer;
it is expected that there will be
8,500 new cases
of the disease diagnosed
in the United States in 2016.
Urothelial carcinoma
is the most common type of bladder cancer, which is the
fifth most commonly diagnosed cancer
in the United States ( 3)
ninth most commonly diagnosed cancer
worldwide ( 8).
and the
