25 | A phase II, open-label study to improve compliance and time of treatment after obtaining complete response through a tailored schedule of sonidegib in locally advanced basal cell carcinomas – the SONIBEC trial

Monica Variolo^1|2, Carlo Resteghini^1|2, Sara Farinatti^1|2, Andrea Alberti³, Valeria Tovazzi³, Paola Queirolo⁴, Maristella Saponara⁴, Giuseppe Argenziano⁵, Riccardo Marconcini⁶, Ketty Peris⁷, Paola Savoia⁸, Maria Chiara Tronconi¹, Iris Zalaudek⁹, Paolo Ascierto¹⁰, Francesco Spagnolo¹¹, Luigi Lorini¹, Cristina Gurizzan¹, Paolo Bossi^1|2 | ¹Medical Oncology and Haematology Unit, IRCCS Humanitas Research Hospital, Rozzano ^MI; ²Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan; ³Medical Oncology Unit, ASST Spedali Civili, Brescia; ⁴Division of Medical Oncology for Melanoma, Sarcoma, and Rare Tumors, IEO, European Institute of Oncology IRCCS, Milan; ⁵Unit of Dermatology, Luigi Vanvitelli University of Campania, Naples; ⁶Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa; ⁷Institute of Dermatology, Catholic University of the Sacred Heart, Rome, Italy; Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome; ⁸Department of Health Sciences, University of Eastern Piedmont, Novara; ⁹Department of Dermatology and Venereology, University of Trieste, Ospedale Maggiore, Trieste; ¹⁰Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples; ¹¹Department of Medical Oncology, IRCCS AOU San Martino-Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.

Background: Sonidegib is an effective treatment for laBCC, but it is associated with a risk of treatment-related adverse events (TRAEs), causing treatment discontinuation. Following a CR, treatment discontinuation rate reaches up to 60% after one year, and the reported 3-year relapse-free survival rate is 35%. We aimed to evaluate sonidegib tailored schedule (TS) after CR to increase treatment duration by reducing TRAEs, possibly allowing longer CR maintenance.

Methods: We conducted a multicenter, open-label, single-arm phase II study enrolling laBCC pts who obtained a CR to sonidegib. Eligible pts received TS1 with sonidegib 14 days on and 14 days off. Pts on TS1 who experienced grade 2-3 toxicity (except alopecia) lasting >28 days moved to TS2 (7 days on and 21 days off). Treatment continued until progression or unacceptable toxicity. Primary endpoint was the rate of pts maintaining sonidegib 12 months after study enrollment (H0 31%, H1 60%). Evaluable pts were defined as all pts who were either on treatment or suspended treatment for reasons other than treatment-unrelated adverse events or death.

Results: Between 01/2021 and 12/2023, 22 pts were enrolled (characteristics in Table 1). Three disease and treatment-unrelated deaths occurred before completing 1 year of TS and therefore 19 pts were evaluable: 12 pts discontinued treatment due to disease progression (26%), sonidegib’s toxicity (11%), personal or physician’s choice (26%). Twelve out of 19 evaluable pts (63%) were still on treatment after 1 year from TS start (median duration 20 months, range 2-29+), meeting the primary endpoint. TRAEs episodes included muscle cramps (13), alopecia (6), and dysgeusia (5), with an overall TRAEs grade of G1 (29), G2 (11), and G3 (3). Twelve pts had dose reduction to TS2.

Conclusions: Tailored maintenance schedule with pulsed sonidegib allows for longer treatment duration and fewer relapses in CR laBCC pts.

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Table 1.