Cancer immunotherapies can effectively tackle many tumor types. But for notoriously hard-to-treat brain cancer—and after a couple of failed trials—hope seems less realistic, at least for Bristol-Myers Squibb’s Opdivo.
A combination of Opdivo and radiation therapy failed to extend the lives of newly diagnosed patients with glioblastoma multiforme when compared with chemo plus radiation in a phase 3 study, BMS said Thursday.
The CheckMate-498 trial failure marks the second glioblastoma shortfall for Opdivo. Back in April 2017, in the first randomized clinical trial that tested a PD-1 immunotherapy in glioblastoma, the drug given solo also fell short. In that trial, Opdivo went up against Roche’s Avastin in patients with a first recurrence and failed to help them live longer.
Hope hasn't been extinguished completely, though. BMS has one more trial to show before its glioblastoma ambitions are officially dashed. The company is also testing Opdivo on top of the current standard of care—radiation plus the chemo regimen known as TMZ—in the 693-patient CheckMate-548 trial, which is expected to read out around 2022.
Glioblastoma is the most common and most aggressive type of central nervous system cancer, with a five-year survival rate of less than 5%. The last drug to show a survival benefit was Merck & Co.’s TMZ, approved by the FDA in the indication in 2005.
Despite the high hopes around PD-1/L1 immuno-oncology therapies, the entire class has had a tough time against glioblastoma. Roche’s Tecentriq, for example, didn’t even get past a small phase 1 in recurrent patients. But MD Anderson Cancer Center is currently collaborating with the NIH’s National Cancer Institute on a phase 1/2 that adds TMZ and radiation therapy to Tecentriq in newly diagnosed patients.
Perhaps immunotherapies that leverage the power of the patient’s own immune system just don’t work well for glioblastoma. A recent study found that the immune cells around glioblastoma tumors have become “exhausted” and therefore couldn't mount a strong enough attack on the tumors, even when checkpoint inhibitors lift the “brakes” on the system.
One small success did emerge earlier this year with Merck’s PD-1 king Keytruda. In a small trial, researchers at the University of California, Los Angeles found that recurrent patients treated with Keytruda before brain tumor removal surgery enjoyed a longer life span than those who got the drug after surgery. Specifically, patients on neoadjuvant Keytruda survived an average of 417 days versus 228 days in the adjuvant group, according to a Nature Medicine study.
Keytruda is already beating Opdivo on the market, as the Merck drug has hogged the lucrative frontline non-small cell lung cancer field. In the first quarter, Keytruda hauled in $2.27 billion in sales, a 60% year-over-year jump at constant currencies, while Opdivo grew 19% to $1.8 billion.
Both drugs have had their fair share of failures lately. Keytruda plus chemo recently didn’t slow cancer progression in previously untreated stomach cancer patients when compared with chemo alone. A pairing of Opdivo and BMS’ own Yervoy also failed a midstage trial in recurrent or metastatic head and neck cancer, the company said in April.