The Standard of Care for Cancer Should be Somatic Sequencing at
Diagnosis
Because the
Standard of Care Should be Better
by John J. Otrompke, JD
Within
five years, tumor sequencing at the time of a patient’s cancer diagnosis will
be the standard of care, according to a number of speakers at several 2020
oncology conferences, including ASCO, BIO and Cancer Progress.
Both
somatic and germline sequencing already form an important part of cancer care,
but too often cancer patients do not receive targeted therapies until they have
failed on other drugs, at which point it might be too late. (Somatic sequencing
is the sequencing of cells from a tumor, while germline sequencing applies to a
patient’s normal DNA).
In 2018, a National
Coverage Determination (NCD) from CMS provided coverage from federal health
payors for somatic sequencing, but it was only conclusive for patients in the
late stages of cancer. (Another
NCD from January 2020 applied to germline sequencing for breast and ovarian
cancer genes).
But it
is important to do sequencing at the time of a patient’s initial diagnosis, so
that patients can receive targeted therapies up-front; oncologists hope that
up-front treatment with the new therapies will reduce acquired tumor resistance,
and substantially improve patients’ results.
When a
patient has experienced an adverse medical result, they can sometimes file suit
against their provider, alleging that the provider was less careful than a
reasonable provider would have been (in other words, that the provider’s
treatment in the case fell below the standard of care). Medical malpractice
cases are usually governed by state law, but in some states, it’s possible that
triers of fact could consider a federal regulation like a NCD in deciding
whether the conduct of an oncologist was reasonable. Under the circumstances
forecasted above, a few years from now, the failure to sequence a patient’s
tumor at diagnosis could render a provider liable for professional negligence.
“Somatic sequencing at the time of
cancer diagnosis will be declared the standard of care within two years. We see
alterations in all solid tumors that mandate molecular profiling in everybody,”
said Ezra Cohen, MD, professor of
medicine at University of California at San Diego.
“I would consider it the standard
of care now for a few cancers, such as acute leukemias and myelodysplastic
syndromes,” added Cohen, who participated in a June 10 session called ‘What Was
Hot at ASCO?’ at the virtual BIO 2020 conference.
Time for a
Scientific Reimbursement Policy
“We have targeted therapies against
several low-frequency alterations that occur, such as NTRK fusions which occur
in up to 3% of lung cancer cases. The response rates to those therapies are 80%
and higher, so not detecting those rare alterations would have a substantial
negative effect on the patient,” added Cohen.
“It would be malpractice for a
patient to come in with suspected cancer and for us not to have the pathologist
look at the tissue and make a diagnosis.
At some point, not doing the fundamental diagnosis to understand cancer
would not be acceptable,” explained Razelle Kurzrock, MD, professor of medicine
at UCSD.
But
notwithstanding the new drugs like entrectinib, larotrectinib and
pembrolizumab, which enjoy tissue-agnostic approval from the FDA under certain
circumstances, the importance of early somatic sequencing has not caught on yet
in some quarters.
“I’m guessing that the majority of cancer
patients in the country are still not sequenced,” said Kurzrock, who is also
co-author of articles such as “Challenging Standard-of-Care
Paradigms in the Precision Oncology Era,” Subbiah V and Kurzrock R (Trends
Cancer. 2018 February ; 4(2): 101–109) (“Between 2003 and 2013, new cancer
drugs approved by the European Medicines Agency (EMA) or the Food and Drug
Administration (FDA) produced a total mean improvement in overall survival of
only 3.4 months relative to the treatments that were available in 2003”).
The recent FDA approval of
pembrolizumab for patients with tumor mutational burden high is a case in
point. “For all intents and purposes, that approval on June 16 requires
sequencing, but the approval is for patients who have failed standard therapy.
It’s not going to be a rationale for sequencing up front,” added Kurzrock, who
noted that the FDA often approves drugs based on studies done in patients who
had already failed other therapies.
“If we’re going to use targeted
therapies, we have to learn the lesson of chronic myeloid leukemia (CML), and
treat at diagnosis. If you wait two or three years to use therapies we know
work on CML, the treatments that give you a 100% response rate and normal life
expectancy will encounter much more resistance, and you might get a life
expectancy of a year,” explained Kurzrock. “Acquired tumor resistance always
happens when you let the cancer evolve.”
