Long‐Term Follow‐up of Parenteral Bevacizumab In Patients with Recurrent Respiratory Papillomatosis

Abstract

ObjectiveThe clinical course of recurrent respiratory papillomatosis (RRP) varies from spontaneous remission to severe airway obstruction with wide variability in recurrence. Standard treatment involves debulking to improve voice and/or breathing. Non‐surgical therapies are emerging in hopes of non‐operative disease control. This retrospective review analyzes long‐term safety, efficacy, and durability of clinical control in the largest reported series of parenteral bevacizumab in adults with RRP.MethodsTwenty‐three patients with known RRP who have been receiving off‐label systemic bevacizumab were included. Dosage, infusion interval, number of cycles, debulking requirements, subjective outcomes, adverse events, and reasons for treatment termination were investigated.ResultsPatients have been followed for an average of 791.43 (21–1468) days. The most common starting dosing regimen was 15 mg/kg at 3 weeks in 11 followed by 10 mg/kg at 6 weeks intervals in 6 individuals. Long‐term maintenance dosage varied with the least intensive regimen being 10 mg/kg at 14‐week intervals. Subjective improvement of voice and/or breathing was reported in 18/23 subjects. The median time for patients that needed a procedure after treatment was 634 days. Procedures after infusions decreased from 3.08 ± 2.48 procedures in the year prior to 0.52 ± 1.12 during systemic Bevacizumab, and to 0.86 ± 2.05 after stopping bevacizumab. Therapy termination occurred in 8 subjects where only 3 were due to adverse events.ConclusionParenteral bevacizumab remains a well‐tolerated treatment for patients with recalcitrant RRP. There appears to be a durable reduction in the frequency of debulking surgery requirements although on a maintenance regimen. Laryngoscope, 133:2725–2733, 2023

Factors Associated with Iatrogenic Laryngeal Injury in Recurrent Respiratory Papillomatosis

“…Systemic bevacizumab has demonstrated ability to nonsurgically manage even the most severe cases of RRP, although therapy must be continued indefinitely. [29][30][31][32] Interestingly, we found in this study that the use of adjuvant bevacizumab, whether local or systemic, was associated with greater risk for iatrogenic laryngeal injury on univariate analyses but not in multivariate analyses. This reflects a selection bias as adjuvant bevacizumab is typically reserved for the most refractory cases of RRP and thus for patients with the highest surgical burden.…”

“…But now, there are emerging options that could potentially reduce the lifetime number of surgeries, regardless of technique, and our result demonstrates the crucial importance of identifying nonsurgical therapies to avoid this iatrogenic damage. Systemic bevacizumab has demonstrated ability to nonsurgically manage even the most severe cases of RRP, although therapy must be continued indefinitely 29‐32 . Interestingly, we found in this study that the use of adjuvant bevacizumab, whether local or systemic, was associated with greater risk for iatrogenic laryngeal injury on univariate analyses but not in multivariate analyses.…”

A case report describing the use of systemic bevacizumab in the treatment of recurrent respiratory papillomatosis with pulmonary involvement

“…The treatment was well tolerated, and the mean follow‐up was 21.6 months. Two recent case series have described promising long‐term response and tolerance in 35 patients with pulmonary RRP treated with systemic bevacizumab 6,7 . Both case series showed that most patients had a sustained response to treatment with a reduction in patient reported symptoms and need for endoscopic procedures.…”

“…Two recent case series have described promising long-term response and tolerance in 35 patients with pulmonary RRP treated with systemic bevacizumab. 6,7 Both case series showed that most patients had a sustained response to treatment with a reduction in patient reported symptoms and need for endoscopic procedures. The most common side effects in both series were hypertension, headache, nausea, and vomiting.…”

Low‐Dose Cisplatin‐Based Radiation Therapy for Refractory Recurrent Respiratory Papillomatosis

“…Furthermore, side effects such as proteinuria, epistaxis, creatinine elevation, hypertension, hemoptysis, hyperthyroidism, and premature menopause occurred in 44% of the patients. 2 Avelumab, a programmed death-ligand 1 (PD-L1) inhibitor, is also reported to result in durable clinical benefit in RRP through induction of antigen-specific T-cell responses. 3 However, these drugs are still under clinical investigation and concrete evidence regarding their effectiveness has not been obtained yet.…”