Does Neoadjuvant Chemoimmunotherapy Boost Survival in NSCLC?

TOPLINE:

Compared with chemotherapy, neoadjuvant chemoimmunotherapy led to better event-free survival and complete responses but not overall survival in patients with resectable non–small cell lung cancer (NSCLC) who had baseline tumor programmed death–ligand 1 (PD-L1) below 1%, a recent meta-analysis found.

METHODOLOGY:

The US Food and Drug Administration (FDA) has approved neoadjuvant chemoimmunotherapy in patients with resectable NSCLC regardless of PD-L1 expression levels, whereas the European Medicines Agency has approved neoadjuvant chemoimmunotherapy in a more restricted population, ie, patients at high risk for recurrence who have PD-L1 expression of 1% or higher.These conflicting approvals highlight ongoing uncertainty surrounding the use of neoadjuvant chemoimmunotherapy in patients with low PD-L1 expression.To clarify the efficacy of neoadjuvant chemoimmunotherapy across patient subgroups, researchers conducted a meta-analysis of 43 studies, including eight randomized controlled trials, with a total of 5431 patients.The researchers compared overall survival, event-free survival, major and complete pathologic responses, and adverse events across all patients and across subgroups, including patients with PD-L1 expression levels below 1%.

TAKEAWAY:

For all patients, regardless of PD-L1 status, neoadjuvant chemoimmunotherapy led to a significant improvement in event-free survival (hazard ratio [HR], 0.59) and overall survival (HR, 0.65) compared with neoadjuvant chemotherapy.Neoadjuvant chemoimmunotherapy was also associated significantly higher odds for major pathologic responses (relative risk [RR], 3.42) and complete response (RR, 5.52).These benefits held across different patient subgroups, except for overall survival in patients with PD-L1 levels below 1%. For patients with baseline tumor PD-L1 levels of less than 1%, neoadjuvant chemoimmunotherapy led to a significant event-free survival benefit (HR, 0.74) but no overall survival benefit (HR, 0.89; 95% CI, 0.66-1.19).Adding immunotherapy to chemotherapy also did not appear to increase the risk for high-grade toxicities, treatment-related adverse events, or serious adverse events.

IN PRACTICE:

Chemoimmunotherapy was associated with an event-free survival benefit in all categories for PD-L1 level but the overall survival benefit “was restricted to the subgroup with a PD-L1 level of 1% or greater,” the authors concluded. This finding provides further evidence to support the restriction in the approval of neoadjuvant chemoimmunotherapy from the European Medicines Agency.

SOURCE:

This meta-analysis, led by Mark Sorin, BSc, from Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, Quebec, Canada, was published online in JAMA Oncology.

LIMITATIONS:

Including nonrandomized trials may have introduced bias. Variability in treatments, definitions for endpoints and differences in follow-up times, and inclusion criteria could have affected outcomes. Also, there may be multiplicity and type I errors due to numerous endpoints tested.