Merck didn’t give AstraZeneca much time to celebrate what was immunotherapy’s only win in biliary tract cancer. The New Jersey pharma has shared detailed results for Keytruda as part of an initial treatment after AZ’s recent FDA approval for Imfinzi.
Adding Keytruda to chemotherapy lowered the risk of death by 17% in patients who had previously untreated advanced or metastatic biliary tract cancer, according to data shared at the American Association for Cancer Research's (AACR's) annual meeting.
The results, from the phase 3 KEYNOTE-966 trial, were simultaneously published in The Lancet. The trial investigators said in the paper that the overall survival improvement was statistically significant and clinically meaningful.
Keytruda’s magnitude of death risk reduction was slightly lower than the 20% Imfinzi put up in its own TOPAZ-1 trial, which won the AZ PD-L1 inhibitor an FDA go-head in front-line biliary tract cancer in September.
But the studies differ in several ways. And by the look of the data, both regimens were far from ideal.
Keytruda’s trial is larger with 1,069 randomized patients, versus the Imfinzi trial’s 685 patients. Because KEYNOTE-966 had a greater proportion of patients enrolled outside Asia than TOPAZ-1 did, its conclusions might be “more representative of the global population,” two researchers at the Royal Marsden Hospital in the U.K. wrote in an accompanying commentary in The Lancet. Biliary tract cancers are much more prevalent in east Asia than in the U.S.
Both trials’ improvements were less impressive than seen in other immunotherapy trials. In KEYNOTE-966, patients on Keytruda and chemo lived a median 12.7 months, versus 10.9 months for chemo alone. In TOPAZ-1, patients who took Imfinzi alongside chemo enjoyed a median overall survival time of 12.8 months, versus 11.5 months in the control group.
The two-year survival rates were almost identical between the two regimens in their respective trials, both at 25%.
However, the Keytruda regimen’s 14% lower risk of disease progression or death compared with chemo missed the statistical significance bar. Imfinzi, in its own trial, delivered a significant 25% reduction on the same marker.
Tumor response rates were also similar between the two arms in the Keytruda trial. But the Keytruda takers experienced a longer duration of response at median 9.7 months, compared with 6.9 months in the control group, the KEYNOTE-966 presenter Robin “Katie” Kelley, M.D., from University of California, San Francisco, noted in a press release facilitated by AACR.
“The durability of responses and proportion of patients with prolonged survival are really meaningful in this difficult-to-treat family of cancers,” Kelley said of Keytruda.
Keytruda’s life-extension benefit appeared similar between PD-L1-expressing tumors and PD-L1-negative cases, the Royal Marsden researchers noted in their commentary.
All told, Kelley said the two trials “both mark significant advances in the field and together validate the role of immune checkpoint inhibition in combination with chemotherapy as first-line therapy” for advanced biliary tract cancers.