New clinical trial results suggest that pemetrexed is effective against some chordoma tumors

Photo: Dr. Santosh Kesari

In a new paper, a team of researchers led by Dr. Santosh Kesari, MD, PhD at Saint John’s Cancer Institute report encouraging results from a pilot study testing the chemotherapy drug pemetrexed (Alimta) for patients with recurrent or advanced chordoma. Of the 14 patients on the trial, 10 had their tumors stabilize or shrink (two had their tumors shrink by more than 30%), and the majority of the patients experienced symptomatic improvements.

“A subset of chordoma patients on the trial had tremendous clinical benefit,” says Dr. Kesari. “We plan to build on our findings about pemetrexed in future clinical trials.”

“Given the limitations of available systemic therapy options for recurrent and metastatic chordomas, this early evidence of activity of pemetrexed is very encouraging,” adds Shreyas Patel, MD, of MD Anderson Cancer Center, who chairs our Medical Advisory Board and is a member of our Board of Directors.

In the current trial, 14% of the patients had a partial response by RECIST criteria — the standard measure of a cancer therapy’s effectiveness based on whether the widest part of a tumor shrinks significantly. To put this in perspective, fewer than 5% of patients experience a comparable response to imatinib (Gleevec) or other drugs which have been evaluated in clinical trials for advanced conventional chordoma. The median progression-free survival was 10.5 months, meaning half of the study participants lived for longer than 10.5 months without their disease progressing. Additionally, patients did not experience any serious or unexpected side effects while on the trial, consistent with the well-established tolerability profile for this FDA-approved drug.

This data suggesting that pemetrexed can control or even shrink some chordoma tumors and improve patients’ quality of life is deeply encouraging, but the results need to be validated in more patients before pemetrexed becomes a standard treatment for chordoma. The new results also suggest an opportunity to test pemetrexed in combination with other treatments that could enhance its efficacy, including certain types of immunotherapies called checkpoint inhibitors. Indeed, pemetrexed plus pembrolizumab (Keytruda) is an effective combination treatment that’s approved for use in certain types of lung cancer, and a clinical trial testing this combination in chordoma is now being planned.

It’s likely that a number of effective drugs and drug combinations will be needed in order for all advanced-stage chordoma patients to benefit from drug therapy, and we still have a lot to learn about how drugs with signs of efficacy in chordoma can be applied in a personalized way. To that end, we recently invested in six projects focused on identifying new treatment opportunities for chordoma, and work is ongoing in Chordoma Foundation Labs to uncover insights about mechanisms of sensitivity and resistance to drugs that are showing signs of promise against chordoma.

Meanwhile, patients are encouraged to contact their doctor or our Patient Navigators with questions about drug therapy options.

We’re thankful to everyone who made this trial possible: the investigators, patients who participated, Eli Lilly and Company who donated the drug supply, and our donors.