Interim analysis of the multinational, post-authorization safety study (NISSO) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma
Abstract Background Following the pivotal phase II trial BOLT, the Hedgehog (Hh) inhibitor sonidegib was approved in the EU to treat locally advanced basal cell carcinoma (laBCC) in patients not amenable to surgery or radiotherapy. We report safety data from the interim analysis of the real-world NI...
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BMC
2024-11-01
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| Online Access: | https://doi.org/10.1186/s12885-024-13101-z |
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| author | Ralf Gutzmer Ulrike Leiter Peter Mohr Katharina C. Kähler Paolo Antonio Ascierto Massimiliano Scalvenzi Ketty Peris Gemma María Pérez-Pastor Ricardo Fernández-de-Misa Rafael Botella-Estrada Robert E. Hunger Serena Martelli Nur Güneli Ramon Arntz Axel Hauschild |
| author_facet | Ralf Gutzmer Ulrike Leiter Peter Mohr Katharina C. Kähler Paolo Antonio Ascierto Massimiliano Scalvenzi Ketty Peris Gemma María Pérez-Pastor Ricardo Fernández-de-Misa Rafael Botella-Estrada Robert E. Hunger Serena Martelli Nur Güneli Ramon Arntz Axel Hauschild |
| author_sort | Ralf Gutzmer |
| collection | DOAJ |
| description | Abstract Background Following the pivotal phase II trial BOLT, the Hedgehog (Hh) inhibitor sonidegib was approved in the EU to treat locally advanced basal cell carcinoma (laBCC) in patients not amenable to surgery or radiotherapy. We report safety data from the interim analysis of the real-world NISSO study. Methods NISSO is an ongoing non-interventional, multinational, post-authorization safety study (NCT04066504). Patients with laBCC are treated with sonidegib 200 mg orally once daily and followed for 3 years. Dose modifications were allowed according to the local prescribing information. Results Between May 6, 2019, and March 15, 2022, 321 patients with laBCC were enrolled at 46 European sites (data cut-off: June 22, 2023). Treatment was discontinued in 241 (75.1%) patients, with the main reasons being the patient/guardian decision (n = 69, 28.6%), treatment success (n = 40, 16.6%) and the physician decision (n = 35, 14.5%). The median duration of sonidegib exposure was 8.8 months (4.4–13.7 months). Overall, 284 (88.5%) patients had ≥ one treatment-emergent adverse event (TEAE). Most TEAEs were ≤ grade 2 and the most common were muscle spasms (n = 141; 43.9%), dysgeusia (n = 119; 37.1%), and alopecia (n = 97; 30.2%). After 3 months of treatment, the cumulative rates of muscle spasms, dysgeusia, and alopecia were 21.8%, 16.2%, and 3.7%, respectively. TEAEs led to treatment discontinuation in 59 (18.4%) patients, while 149 (46.4%) patients had at least one TEAE leading to dose reduction or interruption. Serious drug-related TEAEs were reported in 13 (4.1%) patients. Conclusions These results confirm the safety profile previously observed. Most patients experienced the onset of common TEAEs after 3 months of treatment, and the cumulative incidence of most common TEAEs was 10–20% lower compared to the BOLT study, except for dysgeusia and fatigue that had a similar incidence. The percentage of patients experiencing TEAEs requiring interruption or dose reduction was similar to the BOLT study, while the proportion of patients with TEAE leading to discontinuation of sonidegib was lower. This study demonstrates that the tolerability of sonidegib is manageable in routine clinical practice. Trial registration. NCT04066504. |
| format | Article |
| id | doaj-art-f6af041d3b7c44cf9ec6506be11d5de8 |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj-art-f6af041d3b7c44cf9ec6506be11d5de82024-11-17T12:32:39ZengBMCBMC Cancer1471-24072024-11-012411910.1186/s12885-024-13101-zInterim analysis of the multinational, post-authorization safety study (NISSO) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinomaRalf Gutzmer0Ulrike Leiter1Peter Mohr2Katharina C. Kähler3Paolo Antonio Ascierto4Massimiliano Scalvenzi5Ketty Peris6Gemma María Pérez-Pastor7Ricardo Fernández-de-Misa8Rafael Botella-Estrada9Robert E. Hunger10Serena Martelli11Nur Güneli12Ramon Arntz13Axel Hauschild14Universitätsklinik für Dermatologie, Venerologie, Allergologie und Phlebologie, Johannes Wesling KlinikumUniversitäts-Hautklinik TübingenElbe KlinikumDepartment of Dermatology, University of KielUnit of Melanoma Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione G. PascaleDepartment of Dermatology, University of Naples Federico IIDermatologia, Dipartimento Di Medicina E Chirurgia Traslazionale, Università Cattolica del Sacro CuoreServicio de Dermatologia, Hospital General Universitario de ValenciaHospital Universitario Nuestra Señora de CandelariaHospital Universitario La Fe DermatologíaDepartment of Dermatology, Inselspital, Bern University Hospital, University of BernSun Pharmaceutical Industries B.VSUN Pharmaceuticals Germany GmbHSun Pharmaceutical Industries B.VDepartment of Dermatology, University of KielAbstract Background Following the pivotal phase II trial BOLT, the Hedgehog (Hh) inhibitor sonidegib was approved in the EU to treat locally advanced basal cell carcinoma (laBCC) in patients not amenable to surgery or radiotherapy. We report safety data from the interim analysis of the real-world NISSO study. Methods NISSO is an ongoing non-interventional, multinational, post-authorization safety study (NCT04066504). Patients with laBCC are treated with sonidegib 200 mg orally once daily and followed for 3 years. Dose modifications were allowed according to the local prescribing information. Results Between May 6, 2019, and March 15, 2022, 321 patients with laBCC were enrolled at 46 European sites (data cut-off: June 22, 2023). Treatment was discontinued in 241 (75.1%) patients, with the main reasons being the patient/guardian decision (n = 69, 28.6%), treatment success (n = 40, 16.6%) and the physician decision (n = 35, 14.5%). The median duration of sonidegib exposure was 8.8 months (4.4–13.7 months). Overall, 284 (88.5%) patients had ≥ one treatment-emergent adverse event (TEAE). Most TEAEs were ≤ grade 2 and the most common were muscle spasms (n = 141; 43.9%), dysgeusia (n = 119; 37.1%), and alopecia (n = 97; 30.2%). After 3 months of treatment, the cumulative rates of muscle spasms, dysgeusia, and alopecia were 21.8%, 16.2%, and 3.7%, respectively. TEAEs led to treatment discontinuation in 59 (18.4%) patients, while 149 (46.4%) patients had at least one TEAE leading to dose reduction or interruption. Serious drug-related TEAEs were reported in 13 (4.1%) patients. Conclusions These results confirm the safety profile previously observed. Most patients experienced the onset of common TEAEs after 3 months of treatment, and the cumulative incidence of most common TEAEs was 10–20% lower compared to the BOLT study, except for dysgeusia and fatigue that had a similar incidence. The percentage of patients experiencing TEAEs requiring interruption or dose reduction was similar to the BOLT study, while the proportion of patients with TEAE leading to discontinuation of sonidegib was lower. This study demonstrates that the tolerability of sonidegib is manageable in routine clinical practice. Trial registration. NCT04066504.https://doi.org/10.1186/s12885-024-13101-zBasal cell carcinomaHedgehog pathway inhibitorsSonidegib |
| spellingShingle | Ralf Gutzmer Ulrike Leiter Peter Mohr Katharina C. Kähler Paolo Antonio Ascierto Massimiliano Scalvenzi Ketty Peris Gemma María Pérez-Pastor Ricardo Fernández-de-Misa Rafael Botella-Estrada Robert E. Hunger Serena Martelli Nur Güneli Ramon Arntz Axel Hauschild Interim analysis of the multinational, post-authorization safety study (NISSO) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma BMC Cancer Basal cell carcinoma Hedgehog pathway inhibitors Sonidegib |
| title | Interim analysis of the multinational, post-authorization safety study (NISSO) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma |
| title_full | Interim analysis of the multinational, post-authorization safety study (NISSO) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma |
| title_fullStr | Interim analysis of the multinational, post-authorization safety study (NISSO) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma |
| title_full_unstemmed | Interim analysis of the multinational, post-authorization safety study (NISSO) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma |
| title_short | Interim analysis of the multinational, post-authorization safety study (NISSO) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma |
| title_sort | interim analysis of the multinational post authorization safety study nisso to assess the long term safety of sonidegib in patients with locally advanced basal cell carcinoma |
| topic | Basal cell carcinoma Hedgehog pathway inhibitors Sonidegib |
| url | https://doi.org/10.1186/s12885-024-13101-z |
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