Cancer: Highly personalized therapy can improve outcomes

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By Maria Cohut 

Fact checked by Gianna D’Emilio

The findings of a new study
suggest that people who receive highly personalized combination therapy for
treatment-resistant cancer can experience improved disease control and survival
Recently, precision medicine
has been gaining ground as a potentially more effective approach to treating a
range of stubborn conditions and diseases, including many forms of cancer.
With this type of approach,
researchers aim to better anticipate which types of treatments would best suit
an individual, depending on their genetic makeup and the environmental and
lifestyle factors that are relevant to them.
A new study — the findings of
which appear in the journal Nature Medicine — now suggests that further
personalizing precision medicine may be useful in treating cancers that do not
respond to commonly prescribed therapies.
The researchers, many of whom
are from the University of California, San Diego, in La Jolla, conducted a
clinical trial to test whether personalized combination therapy can have a
positive effect in people with refractory tumors. These are tumors that did not
respond to previous treatment.
In order to find the best
combination therapy match, they analyzed the participants’ specific tumor
mutations and tried to target them individually.
“Response rates to
therapies that target one alteration can be low and not durable,” notes
first author Dr. Jason K. Sicklick. “Our approach went beyond targeting a
single alteration. In collaboration with a multispecialty team of oncology
experts, we formulated a personalized combination therapy for each
patient,” he explains.
“With this approach, we
saw an increased response rate, as well as improved overall survival and
progression-free survival in patients who were highly matched to treatment,
versus those who were unmatched or less well-matched.”
-Dr. Jason K. Sicklick
Results of the prospective

For their prospective study —
which they called the Investigation of Profile-Related Evidence Determining
Individualized Cancer Therapy (I-PREDICT) — the researchers recruited
participants with metastatic cancer. Each had previously received treatment at
one of two oncology centers: the Moores Cancer Center in La Jolla, CA, or the
Avera Cancer Institute in Sioux Falls, SD.
In total, the team enrolled
149 participants with metastatic, refractory cancer, and they managed to match
73 participants (or 49 percent) with combination therapy.
The researchers were not able
to provide treatment for 66 of the enrolled participants, either because the
disease was progressing quickly or because it was in a very advanced stage.
To find good treatment
matches, the researchers conducted tumor DNA sequencing to identify the
specific mutations in each person’s tumors.
Then, the investigators
consulted a team of specialists, including oncologists, pharmacologists, cancer
biologists, surgeons, and geneticists, who helped them determine the best
treatment combinations and matches.
For a person to be
“highly matched” with a combination therapy, the researchers had to
match over 50 percent of the individual’s tumor mutations to drugs that could
address each.
The investigators report that
half of the highly matched participants responded to the prescribed therapies,
while only 22 percent of those who either had no treatment matches or matches
of a poorer quality responded to treatment.
“Having 50 percent of
patients with heavily pretreated disease responding when highly matched speaks
to the importance of personalized precision medicine combination
approaches,” says the study’s senior author, Dr. Razelle Kurzrock.
“Our next step is to
determine if we can increase the benefit rate further if this strategy is
instituted earlier in the course of the disease,” adds Dr. Kurzrock.

‘No two tumors are exactly the

In total, 83 participants
received treatments, informed by their oncologists’ advice and their own
preferences. Of these, 10 received unpersonalized treatments that did not match
their tumor mutations.
The 73 individuals who
accessed personalized combination therapies received a mix of treatments
including gene product-targeted drugs, hormone therapies, immunotherapies, and
“The percentage of
patients matched was much higher than in most precision medicine studies
because we implemented a team who instituted immediate review of genomic
results, as well as navigators who helped patients and physicians access
clinical trials and off-label [Food and Drug Administration (FDA)]-approved
drugs,” notes one of the study’s lead authors, Dr. Shumei Kato.
There are, nevertheless, many
concerns regarding the feasibility of the new approach. According to Dr.
Sicklick, “Personalized multidrug therapies have not been used as standard
treatment because there are concerns about the safety of administering drug
combinations that have not been previously studied together.”
In the current study, the
researchers monitored the treatment outcomes until a participant’s cancer
developed further, until they no longer tolerated the therapy, or until they
passed away.
At the same time, however, the
first author argues that it is important to lean toward as personalized an
approach to cancer therapy as possible.
combinations are necessary, since no two tumors are exactly the same and so no
two regimens will be the same,” emphasizes Dr. Sicklick.
“Our findings demonstrate
that this approach is feasible and safe when patients are monitored closely and
started on reduced doses,” he suggests.
Yet, the researchers admit
that future clinical studies must further test this method and confirm its
Furthermore, many of the study
team members have acknowledged that they received research funds from various
pharmaceutical and clinical research companies, including Novartis
Pharmaceuticals, Blueprint Medicines, Amgen, and Pfizer.


Kayode Ojo
Kayode Emmanuel Ojo is the Co-Founder and Managing Director at SHEFFA Limited. He is presently studying Computer Science at the National Open University, Victoria Island, Lagos.