- Data unveiled Monday from a Phase 3 study found patients with high levels of a biomarker appeared to derive greater benefit from Bristol-Myers Squibb's Opdivo, particularly when paired with the the pharma's other immunotherapy Yervoy.
- Facing an uphill battle to challenge rival Merck & Co. in advanced lung cancer, Bristol-Myers is betting continued segmentation of patient populations will open an opportunity for its immunotherapy Opdivo to earn a share of the first-line market. Key to that strategy is the company's focus on a biomarker known as tumor mutation burden (TMB), which functions as a count of the number of mutations present in a patient's tumor.
- "Patients populations will continue to segment. You will continue to see the evolution of biomarkers," said Bristol-Myers' chief scientific officer Thomas Lynch at an investor event Monday held during the annual meeting of the American Society of Clinical Oncology.
This year's ASCO conference further solidified the position of Merck's Keytruda (pembrolizumab) as the current immunotherapy of choice for initial treatment of metastatic non-small cell lung cancer.
Researchers unveiled results from two more positive studies of Keytruda, showing the drug helped extend survival for a broader range of patients when used as monotherapy or in combination with chemotherapy. While oncologists still debated which regimen to give patients who express lower levels of a biomarker called PD-L1, Keytruda now has data supporting use in most people with NSCLC.
Keytruda's success ups the challenge for competing companies like Bristol-Myers and Roche.
For Bristol-Myers, a study called CheckMate-227 is the company's primary means of demonstrating Opdivo (nivolumab)'s relevance in first-line lung cancer. Back in April, the pharma read out results which showed a pairing of Opdivo and Yervoy (ipilimumab) cut the risk of disease worsening or death by 42% versus standard chemotherapy among patients with a TMB score of greater than 10 mutations per megabase.
According to new data from a different subset of that study, combining Opdivo with chemotherapy also improved median progression-free survival in patients who were considered PD-L1 non-expressors by about one month.
That result, which was descriptive and not tested as a primary endpoint, didn't much impress.
"This is a relatively pedestrian result, I think, for this patient population," said Thomas Stinchcombe, professor of medicine at the Duke Cancer Institute, in remarks discussing the Bristol-Myers data Monday.
Exploratory data presented by Bristol-Myers, however, appears to bolster the pharma's argument that TMB will prove a useful measure of which patients can benefit from immunotherapy.
Among 129 patients with high TMB scores, 45% treated with Opdivo plus Yervoy, and 27% treated with Opdivo plus chemo had not experienced disease progression at 12 months. For those given chemo alone, the one-year progression-free survival rate was only 8%.
If TMB is more widely adopted as a biomarker in clinical practice, Bristol-Myers could argue its combination should play a role in the initial treatment of NSCLC.
"For patients who have no PD-L1 but also have a high tumor mutation burden, I think there is certainly rationale to nivolumab plus ipilimumab without additional chemotherapy," said Leena Gandhi, associate professor of medicine at the New York University School of Medicine, in a plenary session at ASCO Sunday before the new CheckMate-227 data was released.
(Gandhi, who served as principal investigator of Merck's Keynote-189 study testing Keytruda together with chemotherapy, will soon be joining Eli Lilly to lead immuno-oncology medical development.)
Analysts, however, see much of the market going Merck's way. Investment firm Cowen forecasts Keytruda will hold about 50% of the U.S. market by 2019 versus only 13% for Bristol-Myers.
Roche, which is pinning its hopes on a four-drug combination with its PD-L1 inhibitor Tecentriq, is set to claim 31%, according to Cowen.
CheckMate-227 will continue to test Opdivo plus Yervoy's impact on overall survival in patients who express PD-L1.