| Immunotherapy drugs such as Merck & Co.’s Keytruda and Opdivo from Bristol Myers Squibb Co. have transformed cancer treatment in recent years, boosting survival rates for numerous types of tumors. They also cost more than $200,000 a year in the US.
Lately, researchers in Europe, India and elsewhere have been exploring using significantly less medicine. One trial in India found that ultra-low doses of immunotherapy boosted survival for head and neck cancer patients, while a recent small study in the US hinted that reduced quantities also may work in advanced skin cancer. Trials of other dose-sparing strategies are underway in Europe.
A few days ago, additional positive data on lower doses was presented at the European Society for Medical Oncology in Germany. In a 157-person trial done in India, doctors found that using less than a tenth of the approved pre-surgical dose of Keytruda could substantially boost the number of triple negative breast cancer patients that were totally free of cancer after an operation, as compared with not having Keytruda at all.
Meanwhile, a second trial at the meeting from researchers in the Netherlands looked at stopping drugs like Keytruda or Opdivo after roughly six months in melanoma patients whose tumors had shrunk substantially. They’re typically treated for at least 24 months. It found that a large majority were alive and still responding after two years, suggesting the curtailed therapy may offer benefits such as fewer treatment visits for patients wanting to try it.
The trials are small and don’t prove that shorter regimens are as good as standard doses. Nonetheless, academic researchers say the results add to a mosaic of findings that lower doses or shorter courses may still be highly potent. That’s good news for patients in places where access to the pricey drugs is limited. “It’s just adding another piece of evidence into the increasing wall of data to support the whole concept,” says Daniel Goldstein, an oncologist at Rabin Medical Center in Israel, who has advocated for using lower “weight-based” dosing for Keytruda.
Merck says it performed extensive clinical studies to determine the optimal dose and duration for Keytruda, the biggest selling drug in the world. New approaches that haven’t been studied as carefully “should be interpreted with caution and may potentially compromise the therapeutic effect,” it says in response to questions about the impact of lower doses. Bristol’s also made the point that some studies, including one in lung cancer, show that curtailing immunotherapy treatment can lead to worse outcomes. The company says it’s difficult to draw conclusions about the melanoma trial due to its limitations. The study didn’t have a control group. Still, some experts are calling for action.
“We urgently need to revisit the dose,” of immunotherapy drugs, says Atul Batra, an oncologist and trial investigator at All India Institute of Medical Sciences, from the ESMO meeting. In an interview, he compared the drugs to traffic cops that direct the immune system, saying patients need just enough to trigger it to fight the cancer.
In Batra’s ESMO trial, 53.8% of women with triple negative breast cancer who received low dose Keytruda plus chemotherapy before surgery were free of cancer after it, a so-called pathologic complete response. That compared to just 40.5% of those who were cancer-free in a control group who got chemotherapy alone.
The study didn’t directly compare low dose to standard dose Keytruda, and the Indian researchers don’t yet have survival data. Countries that can afford the full dose are unlikely to cut it without much more data. Lower doses could help more people access care in countries like India, where many can’t afford immunotherapy today. When I went to India for a story on this subject in May, I met several patients who benefited from reduced dose immunotherapy for various tumors. None could afford the standard dose. “The benefits could be huge” if the lower-dose breast cancer regimen is widely adopted in low- and middle-income countries, Batra said. In India alone, some 40,000 women a year get this type of early stage breast cancer, he estimated. Only a tiny fraction can afford the full dose now, he said. — Robert Langreth and Ashleigh Furlong |
