Which lung cancer patients can benefit from neoadjuvant immunotherapy?

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Which lung cancer patients can benefit from neoadjuvant immunotherapy?

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Which lung cancer patients can benefit from neoadjuvant immunotherapy?

A recent meta-analysis published in JAMA Oncology found that compared to chemotherapy, neoadjuvant chemoradiotherapy can improve the event-free survival and complete response rate of resectable non-small cell lung cancer (NSCLC) patients with a baseline tumor programmed death-ligand 1 (PD-L1) expression of less than 1%, but does not improve overall survival.

The U.S. FDA has approved neoadjuvant chemoradiotherapy in resectable NSCLC patients regardless of PD-L1 expression level. However, the European Medicines Agency has approved neoadjuvant chemoradiotherapy in a more limited population, specifically in patients with PD-L1 expression of 1% or higher at high risk of recurrence.

These conflicting approvals highlight the ongoing uncertainty surrounding the use of neoadjuvant chemoradiotherapy in patients with low PD-L1 expression.

To clarify the effectiveness of neoadjuvant chemoradiotherapy in patient subgroups, researchers conducted a meta-analysis of 43 studies, including 8 randomized controlled trials, totaling 5431 patients.

Researchers compared overall survival, event-free survival, major and complete pathological responses, and adverse events, including in patients with PD-L1 expression levels below 1%.

All patients

For all patients, regardless of PD-L1 status, neoadjuvant chemoradiotherapy significantly improved event-free survival (hazard ratio [HR], 0.59) and overall survival (HR, 0.65) compared to neoadjuvant chemotherapy. The probability of major pathological response (relative risk [RR], 3.42) and complete remission (RR, 5.52) with neoadjuvant chemoradiotherapy also significantly increased. These benefits were observed in different patient subgroups except for the overall survival of patients with PD-L1 levels below 1%.

Patients with low PD-L1 expression

For patients with a baseline tumor PD-L1 level below 1%, neoadjuvant chemoradiotherapy resulted in a significant benefit in event-free survival (HR, 0.74), but not in overall survival (HR, 0.89; 95% CI, 0.66-1.19).

Safety

Adding immunotherapy to chemotherapy also did not seem to increase the risk of high-grade toxicity, treatment-related adverse events, or serious adverse events.

Conclusion

“In patients with any PD-L1 level, neoadjuvant chemoradiotherapy is associated with event-free survival benefit, but overall survival benefit is ‘limited to the subgroup with PD-L1 levels of 1% or higher,'” the authors concluded.

This finding provides further evidence supporting the restrictions imposed by the European Medicines Agency on the approval of neoadjuvant chemoradiotherapy.

Which lung cancer patients can benefit from neoadjuvant immunotherapy?

References:

[1] Banna GL, Hassan MA, Signori A, et al. Neoadjuvant Chemo-Immunotherapy for Early-Stage Non–Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2024;7(4):e246837. doi:10.1001/jamanetworkopen.2024.6837

(source:internet, reference only)

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