Locally advanced basal cell carcinoma can be a difficult-to-treat disease, particularly in areas such as the face that are sensitive to mutilating surgery or radiotherapy. Hedgehog inhibitors including sonidegib that are administered orally once daily have been developed for the treatment of these patients. The case reports detailed here relate to two over 90-year-old female patients with facial basal cell carcinomas. Their advanced age, comorbidities, and tumor locations close to the eye and on the nose precluded extensive surgery or irradiation. Treatment with sonidegib 200 mg led to rapid and lasting responses, with complete or near-complete regression that eventually enabled curative surgery in one case and preservation of the right eye in the other. Side effects occurred infrequently and were managed using symptomatic therapies as well as dose modification. In addition to surgery and irradiation, sonidegib is an effective and tolerable treatment option for locally advanced basal cell carcinoma that can be expected to work in any age group.
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Introduction
Basal cell carcinoma (BCC) is the most common type of skin cancer and the most common cancer worldwide [1]. Although it rarely metastasizes, the treatment of locally advanced BCC can be challenging, particularly in areas such as the face, where surgery or radiotherapy might give rise to disfigurement and/or loss of function. Based on the double-blind phase II BOLT trial, the hedgehog pathway inhibitor sonidegib has been approved for the treatment of adult patients with locally advanced BCC that is not amenable to curative resection or irradiation [2].
Patients receiving sonidegib 200 mg daily in the BOLT study achieved sustained and clinically relevant responses, with a 42-month objective response rate of 56.1% according to central review [3]. Adverse events observed with sonidegib most frequently comprised muscle spasms, alopecia, dysgeusia, and nausea.
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Although it rarely metastasizes, the treatment of locally advanced basal cell carcinoma can be challenging
The case reports discussed here illustrate the efficacy and tolerability of sonidegib in two female patients with inoperable BCC. Both women were over 90 years old.
Case Report 1
The first patient was initially seen in February 2022 at the age of 96. Completion of the diagnostic workup was deferred due to her advanced age. In 2023, when a full diagnosis was finally made, the patient had an expansive BCC at the inner corner of her right eye, which, according to computed tomography (CT), had spread to the nasolacrimal duct but not to the bone (Fig. 1). Another lesion was present at the left nasal wing. Punch biopsies confirmed the diagnosis of BCC in both areas. The patient had hypertension and Parkinson’s disease, which were treated with appropriate medication.
Fig. 1
Patient 1: expansive basal cell carcinoma at the inner corner of the right eye and another lesion on the left nasal wing
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As these lesions were not amenable to surgery, the tumor board recommended the administration of a hedgehog inhibitor. Sonidegib 200 mg 1‑0‑0 was started in June 2023. After just 2 weeks, the orbital tumor showed signs of regression, and after 7 weeks, both tumors had diminished in size. Continuous regression followed until, at week 32, only tiny nodular residuals were found at the inner corner of the right eye and the entire lesion at the left nasal wing had been replaced by scar tissue (Fig. 2).
Fig. 2
Patient 1: regression of both lesions, with tiny nodular residuals at the inner corner of the eye and complete response of the lesion on the nasal wing after 32 weeks of sonidegib treatment
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As the lesions were not amenable to surgery, administration of a hedgehog inhibitor was recommended
Sonidegib therapy proved tolerable. At week 11, the patient reported recurring nausea and epigastric pain that were treated with ondansetron and proton pump blocker therapy. Four weeks later, the gastrointestinal symptoms had subsided. However, at week 20, nausea reemerged, and the amylase level rose to 121 U/L, while lipase levels remained stable. Therefore, the dose of sonidegib was reduced to 200 mg 1‑0‑0 every other day, which resulted in normalization of the amylase level 4 weeks later. The patient reported normal appetite without nausea, but also onset of hair loss.
Between weeks 30 and 40, the patient did not take sonidegib due to a COVID-19 infection. Nevertheless, her tumor response persisted. Meanwhile, she is back on sonidegib 200 mg 1‑0‑0 every other day and is being monitored on a regular basis.
Case Report 2
The second patient had undergone surgery for BCC on the bridge of her nose in 2003. In September 2023, at the age of 93, she presented with massive recurrent BCC that showed infiltration of the nasal cartilage on both sides and extension to the right-sided preseptal orbital area according to CT (Fig. 3). Also, the CT findings indicated spreading of tumor tissue to the nasal septum. Histological workup confirmed the diagnosis. Comorbidities included a history of stroke, chronic venous insufficiency of both legs, diabetes mellitus type II, and coronary heart disease. The patient was receiving treatment with a beta-blocker, acetylsalicylic acid, and rilmenidine.
Fig. 3
Patient 2: huge recurrence of a basal cell carcinoma that had been removed from the bridge of the nose 20 years previously
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Upon recommendation of the tumor board, hedgehog inhibition with sonidegib 200 mg 1‑0‑0 was commenced in September 2023. The tumor size decreased within 3 weeks. At week 19, complete clinical regression accompanied by a post-therapeutic tissue defect had occurred on the right nasal wing, while the left nasal wing carried a receding tumor node (Fig. 4). A CT scan of the facial skull revealed that apart from a small lesion on the bridge of the nose that showed contrast agent uptake, the tumor tissue had completely disappeared. After further regression of the lesion on the left nasal wing, sonidegib therapy was discontinued in week 30, and the residual cancerous tissue was removed and replaced by a full-thickness skin graft under local anesthesia. Figure 5 shows the result 6 weeks after surgery.
Fig. 4
Patient 2: complete clinical regression accompanied by a post-therapeutic tissue defect on the right nasal wing and receding tumor node on the left nasal wing after 19 weeks of sonidegib treatment
Fig. 5
Patient 2: 6 weeks after surgical removal of residual basal cell carcinoma tissue and replacement by a full-thickness skin graft
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The tumor size decreased within 3 weeks of treatment with sonidegib
Sonidegib treatment did not give rise to any adverse events until week 15. At that time, the patient reported recurring pruritus of her entire integument that was treated successfully with levocetirizine and olive oil ointment, while sonidegib therapy was continued. All laboratory assessments showed unremarkable findings.
Discussion
In the first patient described herein, who had BCC of the orbit, both surgery and irradiation would most likely have induced vision loss in the right eye or at least a reduction in vision. Sonidegib 200 mg once daily led to rapid and near-complete regression of the orbital lesion as well as a complete response of the lesion on the left nasal wing. These responses even persisted for many weeks after the patient had stopped treatment due to a COVID-19 infection.
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In the case of the second patient whose nose was completely disfigured by an expansive BCC, sonidegib therapy for 30 weeks achieved operability, thus enabling freedom from disease that prevails to date. Apart from the location of the lesions, advanced age and relevant comorbidities precluded local treatment in both patients.
These observations are in keeping with the results obtained for sonidegib 200 mg per day in the pivotal BOLT trial that showed high response rates and durable responses regardless of tumor burden at baseline [3]. The adverse events emerging in our patients matched those reported in the study and were manageable with symptomatic treatment and dose modification. Reducing the sonidegib dose to 200 mg every other day in the first patient did not diminish treatment efficacy while it did increase tolerability and facilitate long-term use. Moreover, the oral intake of one pill per day represents a most uncomplicated mode of administration.
Conclusion
Treatment with the hedgehog inhibitor sonidegib 200 mg daily has given rise to rapid and impressive tumor responses in the two very old patients with facial BCC discussed herein. Adverse events occurred rarely and were easily manageable with local treatment and dose modification. Sonidegib represents an effective and tolerable treatment option for advanced BCC in addition to surgery and irradiation, even at a very advanced age.
Acknowledgements
The author would like to thank Judith Moser MD for medical writing support.
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Declarations
Conflict of interest
A. Stepan states the following conflicts of interest: Honoraria: Astro-Pharma.
For this article no studies with human participants or animals were performed by any of the authors. All studies mentioned were in accordance with the ethical standards indicated in each case. Additional informed consent was obtained from all individual participants from whom identifying information is included in this article.
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