Bristol Myers Squibb has expanded Opdivo’s first-in-class win in pre-surgery non-small cell lung cancer, teeing up a potential FDA filing.
Opdivo added to chemotherapy before surgery in the so-called neoadjuvant setting lowered the risk of tumor recurrence, progression or death in patients with resectable stage IB to IIIA non-small cell lung cancer, BMS said Monday.
The latest event-free survival win adds to a previous success from the same phase 3 trial where Opdivo plus chemo helped significantly more patients have no signs of cancer cells in their resected tissue—a marker called pathologic complete response—compared to chemo alone when given before surgery. The CheckMate-816 trial has therefore met both its co-primary endpoints.
The FDA has previously used pathologic complete response as a surrogate endpoint to grant accelerated approval for Roche’s Perjeta, in combo with Herceptin and chemo, for the neoadjuvant treatment of HER2-positive early-stage breast cancer. Event-free survival, while also a surrogate marker, offers a more mature look at a neoadjuvant treatment’s efficacy from a clinical trial.
Event-free survival has supported traditional FDA go-aheads. Merck recently convinced FDA to change a previous complete response letter into a full approval for Keytruda’s use both before and after surgery in early triple-negative breast cancer after the New Jersey pharma turned in more mature event-free survival data.
And, just last month, the FDA cleared Roche’s Tecentriq and chemo as post-surgery treatment for PD-L1-positive, stage II to IIIA NSCLC based on disease-free survival data. That approval marks the first for a cancer immunotherapy in the adjuvant NSCLC area.
Opdivo is the first immunotherapy to boast a phase 3 win for neoadjuvant treatment of non-metastatic NSCLC, Abderrahim Oukessou, M.D., BMS’ thoracic cancers development lead, said in a statement.
The cancer care community has long debated whether neoadjuvant or adjuvant immunotherapy is better for early cancer. The rationale for neoadjuvant use of PD-1/L1 inhibitor is that the presence of a tumor—a target—may induce a strong immune response, BMS pointed out.
But adding early immunotherapy on top of chemo before surgery has some doctors nervous about making patients less fit for an operation.
A previous update from CheckMate-816 showed that 83% of patients who got the Opdivo combo underwent definitive surgery, versus 75% for chemo alone. Other assessments such as the conversion from minimally invasive to open surgery rates were roughly similar between the two groups, as the researchers concluded that neoadjuvant Opdivo didn’t delay or prevent surgery nor did it hurt the extent of resection.
As SVB Leerink analyst Daina Graybosch, Ph.D., observed in a September note after discussions at the European Society for Medical Oncology annual meeting, doctors seem to be shifting toward favoring neoadjuvant immuno-oncology treatment over adjuvant use. As neoadjuvant immunotherapies require shorter treatment periods, their increased use would “significantly limit expansion opportunity for all checkpoint therapies in early-stage settings,” she wrote.