Pfizer Inc.’s Xalkori, a drug that targets lung cancer caused by a gene defect, wiped out all signs of malignancy in some children with different tumor types, in a study that proves aiming treatment at genes rather than disease sites may be more effective.
The findings, being released today in advance of the American Society of Clinical Oncology meeting that starts June 1, tested the medicine against rare child tumors of the nerves, blood and soft tissue that can be driven by mutations in the ALK gene targeted by Xalkori. The drug helped kids with all three tumors, with the most impressive results seen in a blood cancer called anaplastic large cell lymphoma. In these cases, all signs of cancer vanished in 7 of 8 kids who got the drug.
The results show how gene-targeted medicines first tested in one cancer can rapidly be applied to other malignancies with the same gene abnormality. By identifying the genetic drivers of pediatric tumors, scientists may be able to take targeted drugs already approved for adults and apply them to children.
“This is a glimpse of the new paradigm” of cancer drug development, said Michael Link, a Stanford University pediatric cancer specialist and president of the American Society of Clinical Oncology, on a conference call. By understanding the molecular drivers of the tumors, “we have the prospect of seeing dramatic responses.”
In an interview, Link called the preliminary results “really extraordinary.”
The Pfizer drug also eliminated measurable signs of cancer in 2 of 27 kids with neuroblastoma, a rare nerve cell cancer, who had failed standard therapy. The drug also shrank tumors in 2 of 7 children with inflammatory myofibroblastic tumor, a rare malignancy of soft tissues.
The trial was sponsored by the government-funded Children’s Oncology Group, a consortium of experts, children’s hospitals, cancer centers and universities, and also received support from New York-based Pfizer (PFE:US), the world’s largest drugmaker.
While it is far too soon to tell if any of the children are cured, “these are very promising results for kids who historically have had very few options and no hope,” Yael Mosse, a pediatric oncologist at the Children’s Hospital of Philadelphia and the study’s lead researcher, said in an interview. “They have their whole lives ahead of them.”
About 120 kids in the U.S. each year develop ALK-positive lymphoma, while 100 get neuroblastoma that contains defects in the ALK gene, Mosse said.
Advanced Testing Planned
Mosse said the researchers plan to begin a final-stage trial of the Pfizer drug in kids with lymphoma by the end of the year. The goal is to use the Pfizer drug for all children newly diagnosed with this type of lymphoma and replace some of the toxic chemotherapy that is used today, she said.
It is “a major opportunity” to lessen the intensity of chemotherapy so that cure comes at less of a cost, she said.
Zach Witt is one child who was helped by the drug, said his mother Pam Witt, who lives in outer suburbs of Philadelphia, in a phone interview. The 6-year-old developed lymphoma in September 2010 and relapsed in the middle of his chemotherapy treatment in early April of 2011.
He soon developed high fevers and became so weak that he couldn’t make it to the hospital playroom just down the hall from his room, she said.
Doctors at the Children’s Hospital of Philadelphia gave her and her husband a choice of putting Zach on a more toxic chemo regimen or going into the trial of Xalkori. They chose the Xalkori.
Being a Kid Again
By the third day on the drug, Zach was running to the hospital playroom, she said. Today he is out of the hospital, and “does everything any other kid would do,” she said. He is so energetic he recently went on a 21-mile bike ride with his father, she said.
“I don’t think Zach would be here” without the Pfizer drug, she said.
Child and adult cancer drug testing “used to operate in separate universes,” said Rob Sweetman, a senior director at Pfizer’s cancer unit. “Now we understand these molecular drivers that are connecting these two that weren’t as obvious before.”
Sweetman said Pfizer is carefully monitoring the progress of the child trials and will make a determination whether to seek regulatory approval for the child uses when more data is available.
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