A gene-targeted drug sold by Eli Lilly can shrink tumors in a wide range of cancer types, not just the lung and thyroid malignancies in which the DNA mutations it's aimed at are most prevalent, new study results show.
Treatment with the drug, called Retevmo, led to tumor responses in nearly half of 32 participants studied in the trial, who collectively had 12 different types of cancer.
The finding, while from a small group of patients, could begin to build a case for using Retevmo to treat cancers based solely on their genes rather than location within the body. Only three drugs, including one developed by the biotech company Lilly bought to acquire Retevmo, have received such so-called tissue agnostic approvals from the Food and Drug Administration. All three OKs have come since 2017, reflecting rapid advances in the development of gene-targeting cancer medicines. Several others could follow.
In Retevmo's case, the gene in question is known as RET and, when abnormally fused to another gene, can spur tumor growth. These RET fusions are found in about 2% of non-small cell lung cancers and between 10% to 20% of papillary and other thyroid cancers, tumor types which the FDA approved Retevmo to treat in May of last year.
"We also see RET fusions in a long tail of solid tumors beyond lung and thyroid," said Vivek Subbiah, an oncologist at the University of Texas MD Anderson Cancer Center and lead researcher on the study. "These are difficult-to-treat cancers and these patients don't have an approved targeted therapy to address the underlying genetic fusion of their cancer."
The results presented Sunday are from a subset of the same early-stage study that supported Retevmo's original approval. That trial has now enrolled over 700 patients with cancers either positive for RET fusions or RET mutations.
Among the 32 adults with RET fusion-positive cancers not in the lungs or thyroid who were evaluated, nearly two-thirds had gastrointestinal tumors in the pancreas, colon, intestine or rectum. Most had previously received chemotherapy and about a third had been previously treated with three or more cancer drugs. Half of them had surgery.
Generally, about 10% to 20% of people with these types of tumors would be expected to respond to chemotherapy, Subbiah said.
Treatment with Retevmo, by comparison, led to a confirmed tumor response rate of 47%, across nine different cancer types. For 11 of the 15 patients whose tumors shrank, their cancers remained in check through the study's data cut-off for presentation of results. Median follow-up was just over a year.
In one study participant, a 31-year-old woman with pancreatic cancer, her tumors had grown despite treatment with a common chemotherapy regimen. After she started Retevmo, they shrank by half. She is still responding to the drug a little over three years later.
Lilly said it would discuss the study findings with regulators this year. In an interview, David Hyman, chief medical officer of the company's cancer division, wouldn't speculate whether this current cut of data would be enough to support an application for expanded approval.
But, he said the results do show that RET fusions can drive tumor growth in more than just lung and thyroid cancers.
"The question was, are these RET fusions actionable?" Hyman said. "When you see an overall response rate in the range of 50%, the answer points to, 'Yes, these are leading to oncogene addiction and are potentially targetable.'"
Retevmo is the second drug developed by Loxo Oncology, the biotech bought by Lilly, to win FDA approval. The first, called Vitrakvi and now owned by Bayer, was approved in 2018 for use in any tumor with alterations in a gene called NTRK, regardless of where the cancer is found in the body. The data supporting the approval came from a study of 55 patients.
Yet the commercial potential of these drugs is still uncertain. Use of both depends on whether oncologists test their patients' tumors for the targeted genetic alterations. In some cancers, like those of the lung and skin, tumors are regularly tested for mutations in genes like EGFR, ALK, BRAF and MEK as there are a range of targeted therapies available.
Vitrakvi and Retevmo, by contrast, were the first therapies approved to treat cancers spurred to growth by alterations in NTRK and RET, respectively.
"These therapies are what drive adoption of testing," said Hyman.