Bevacizumab reduces PD-L1 Not PD-1 inhibitor-associated pneumonitis in non-small cell lung cancer patients.

[BACKGROUND] Interstitial pneumonitis (IP) is a severe adverse event in patients receiving immunotherapy. Although PD-1/PD-L1 inhibitors and bevacizumab have been widely used in patients with non-small cell lung cancer (NSCLC), the interaction between their combination and IP is less known.

[METHODS] To investigate the interaction between bevacizumab and PD-1/PD-L1 inhibitors on IP, an observational study between January 2012 and June 2023, US, from the Food and Drug Administration Adverse Event Reporting System (FAERS) database including 55,673 NSCLC patients was performed. The reported proportions of PD-1/PD-L1 inhibitor-associated IP in patients receiving and not receiving bevacizumab treatment were compared.

[RESULTS] A total of 23,790 and 4753 patients were treated with PD-1/PD-L1 inhibitors and bevacizumab, among whom 1693 were treated with both PD-1/PD-L1 inhibitors and bevacizumab. The proportions of IP were 7.3% (95% CI 7.1 to 7.5%) in the total population of patients with NSCLC, 11.1% in patients treated with PD-1/PD-L1 inhibitors, and 4.4% in patients treated with bevacizumab. The reported IP proportion was 15.4% for PD-1 inhibitors with bevacizumab, which was greater than the 9.1% for PD-1 inhibitors without bevacizumab, while the opposite trend was observed for PD-L1 inhibitors (4.4% for bevacizumab vs 19.6% for PD-L1 inhibitors without bevacizumab).

[CONCLUSIONS] Our study showed that bevacizumab was associated with a higher reported proportion of PD-1 inhibitor-associated IP but a lower reported proportion of PD-L1 inhibitor-associated IP. Although this was a post-marketing, observational study with many limitations, bevacizumab might be a proper combination with PD-L1 inhibitors in consideration of IP, especially in patients at high risk of IP. However, this relationship still needs further clinical validation.