A NEW TARGET, A NEW DRUG AND A CHILD IN NEED
In 2015, I was contacted by colleagues in Campo Grande in southwestern Brazil. We met
during my lecture tour and I became friends with their medical and pediatric oncologists.
The pediatric oncologist contacted me to discuss a child with sarcoma. We arranged
tissue transport and processed the tumor in our laboratory.
The results revealed activity for several drugs but I was puzzled by activity for a targeted
agent known as Crizotinib that inhibits genetic changes that include ALK, ROS1, and
more recently NTRK.
The patient at first responded to chemotherapy, but then progressed.
In late 2018, I was again contacted when the physician. The child had brain metastases
and was rapidly deteriorating. They inquired whether I could obtain the new drug
Larotrectinib, an agent related to Crizotinib with very good brain penetration.
The brain lesion was biopsied and a genomic analysis revealed an NTRK gene re-
arrangement. Suddenly our original 2015 findings came into focus. Crizotinib has activity
for NTRK. With our findings and the genomic results I knew these drugs held the key.
The child had an extremely large and rapidly growing mass in the center of her brain. She
required intubation in the ICU. Her prognosis was extremely grave.
The child's father contacted me to ask whether we could procure the drug here in the US.
Quite by chance, Larotrectinib for NTRK had just received FDA approval in November
of 2018 and here barely a month later we had our first candidate.
The problem: Larotrectinib had never been used in South America and was not approved in Brazil.
Undeterred we forged ahead, wrote the prescription and arranged for delivery to a
specialty pharmacy in Santa Monica, California. We reasoned that the father could fly to
LA, buy the drug and bring back to his daughter as she remained on a respirator in Sao
But the father did not speak English. He had never been to the US and felt hesitant to
undertake the trip. How might we get this potentially life-saving drug to this young girl?
As many of you may be aware, we have ongoing collaborations with Brazilian
investigators and our post-doctoral fellow, Dr D’Amora learning of the desperate
situation, offered to travel to the US to procure the drug on behalf of the family.
We arranged his travel. He arrived in LA, drove to the pharmacy purchased the drug and
got back on the plane to Brazil.
The child was in desperate straits, unresponsive on a respirator in the ICU. The
medication was fed through a nasogastric tube.
She improved immediately. I mean immediately! The father contacted me to ask if a
second month’s supply could be procured and Dr D’Amora again traveled to LA to
return with the second month’s drug.
By now the response was dramatic. She came off the respirator, was transferred to the
pediatric ward and began to eat.
Recognizing the miraculous response, the Government of Sao Paulo crafted a special
dispensation and the pharmaceutical company provided the medication free of charge.
Several months later she began first grade.
Every several months thereafter the family sent photographs. First of her in a hospital
bed, then at home with her family, then on her way to her first day of school and finally a
video of her dancing. We approached the pharmaceutical company and suggested that
this miraculous story should be reported.
Despite Dr D’Amora’s heroism, the efforts of referring physician and the family’s
dedication, they would not allow us to discuss the case and non-disclosure agreements
were required, the breech of which would compromise her capacity to have the drug
Recently I was apprised of a Case Report published in the Journal of Clinical Oncology
and Research about a young girl in Sao Paulo who received this therapy. It was our
patient. But, there was no mention of the referring physician who made the diagnosis nor
the efforts of Dr. D’Amora who procured the drug, nor the heroic efforts of the family.
For this case report, it was their football and they were captain.
Now, three years later, the child has recurred. I was again approached by the family and
we have initiated efforts to procure a 3rd generation NTRK inhibitor to save her life.
If we are fortunate she may have a chance. Working with colleagues at a new
pharmaceutical company we hope we can apply for compassionate use.
The story is interesting as it was the unexpected activity for Crizotinib in our laboratory
that triggered the success. Once again, human tissue studies provided critical insights.
With confirmation of the target at a genomic level and sensitivity to this class of drugs in
our lab, response was nearly assured. With 3 years of benefit and the chance of further
response, this confirms the important role of phenotypic analyses in treating rare and