In Response to <i>A Clinical Consensus Statement on Pulmonary Recurrent Respiratory Papillomatosis</i>

We thank Hasan et al. for their thoughtful commentary on our clinical consensus statement on pulmonary manifestations of recurrent respiratory papillomatosis (RRP). We agree that the recent Food and Drug Administration (FDA) approval of zopapogene imadenovec-drba (Papzimeos) marks a significant progression in the treatment of RRP and may decrease the need for additional invasive surgeries and the associated morbidity. However, we would like to clarify a few points: The discussions for our paper began over a year ago at which time zopapogene imadenovec-drba was not available, and final submission occurred prior to its approval by the Food and Drug Administration (FDA). We did, however, highlight the role of systemic therapies including zopapogene imadenovec-drba and INO-3107 in the discussion section of the paper given the recent data. Further, we would like to clarify that we did not definitively recommend a systemic therapy by name, such as bevacizumab, in our consensus statement—we only highlighted the fact that systemic therapy should be considered in the management of pRRP and that bevacizumab is a commonly used systemic treatment for pRRP based on the available data (statements 5.1 and 5.2, respectively). In addition, we would like to highlight the different effects of zopapogene imadenovec-drba and bevacizumab. Bevacizumab can cytoreduce papilloma whereas zopapogene imadenovec-drba can eliminate HPV-infected cells and bevacizumab cannot. Clinically, zopapogene imadenovec-drba has not been proven effective in debulking advanced disease whereas bevacizumab has been effective in inducing clinical responses in symptomatic disease [1]. This speaks to their different mechanisms of action and even suggests a possibly synergistic role, which would benefit from further research. Based on this information, we would not necessarily make a recommendation for one systemic therapy over another as they both have unique roles in the management of RRP. Finally, we do not yet know of the effectiveness of zopapogene imadenovec-drba in broader populations including children and there is no data that reports efficacy in pulmonary disease. In Norberg et al.'s study, there was no clinical effect of zopapogene imadenovec-drba on pulmonary disease in the four patients with pRRP—the best response of zopapogene imadenovec-drba on pulmonary disease was maintaining stable disease [2]. In summary, while zopapogene imadenovec-drba's FDA approval marks an exciting development and may be considered in the treatment of pulmonary RRP along with other systemic therapies, further data are needed to explore its effect on pulmonary disease and to compare this with other systemic therapies. The authors declare no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.