In presurgery treatment of early-stage cancer, there has been much debate over whether the absence of cancer in surgically removed tissue serves as a good indicator of whether treatment will prevent cancer recurrence or death.
Now, Bristol Myers Squibb is adding one piece of evidence to support a link between the two in non-small cell lung cancer (NSCLC).
Among early NSCLC patients who took Bristol Myers’ Opdivo and chemotherapy before surgery and had no trace of tumor in resected tissue, the risk of disease recurrence or death dropped by 82% compared with those who still had traces of tumor at surgery.
The number came from a post hoc analysis of the CheckMate-816 trial presented at the 2022 American Society of Clinical Oncology meeting. Previously, data comparing the Opdivo-chemo regimen against chemo alone on those two efficacy endpoints—known as pathological complete response and event-free survival—earned Opdivo a fast FDA approval in neoadjuvant NSCLC treatment.
The new result is “very suggestive” of an association between achieving pathological complete response (pCR) and having a better outcome in event-free survival for patients who got Opdivo and chemo before surgery, Mark Rutstein, M.D., vice president of Opdivo development at BMS, said in an interview with Fierce Pharma.
BMS saw a “consistent effect” across patients with baseline stages 1B to 3A disease, and regardless of their tumors’ PD-L1 expression levels, Rutstein said. Plus, BMS also noted a correlation between any depth of tumor reduction at surgery—called pathological regression—and two-year event-free survival, he added.
Drawing a clear relationship between a pCR and improvement in event-free survival is important for presurgery drug development. It could mean that an early pCR signal may serve as a surrogate endpoint to support regulatory approval.
The FDA has set out guidance for drugmakers to use pCR to win accelerated approval for pre-surgery treatment of high-risk early-stage breast cancer. In 2013, Roche’s Perjeta won an accelerated approval for neoadjuvant HER2-positive breast cancer based on pCR data, as well as additional support from life extension data in a separate metastatic disease trial.
But the association between pCR during presurgery treatment and event-free survival improvements is still debated across tumor types. For example, in a recent BMJ study, a group of oncologists led by the European Institute of Oncology couldn’t establish pCR as a good surrogate for disease-free survival or overall survival in breast cancer after analyzing data from 32,611 patients enrolled in 54 randomized clinical trials.
A 2020 study involving BMS and Icon researchers recorded a 51% reduction in the risk of death tied to pCR across nearly 6,700 patients in 21 clinical trials of neoadjuvant therapy for resectable NSCLC.
BMS doesn’t expect the new Opdivo data could end the debate.
“Endpoint surrogacy is established usually based on large amounts of data across multiple clinical trials,” Rutstein said. CheckMate-816 is just one trial demonstrating a strong correlation for the Opdivo-chemo regimen, which “can be built upon to take us to that level of regulatory impact,” he said.