Impact of Food and Drug Administration Approval of Vismodegib on Prevalence of Orbital Exenteration as a Necessary Surgical Treatment for Locally Advanced Periocular Basal Cell Carcinoma

Abstract

Purpose: To test the hypothesis that the US Food and Drug Administration approval of vismodegib in early 2012 has reduced the prevalence of orbital exenteration for locally advanced periocular basal cell carcinoma (BCC). Methods: Following institutional review board approval, the authors reviewed clinical and pathological data of patients with locally advanced periocular BCC (T4 per the eyelid carcinoma classification in the 8th edition of the AJCC Cancer Staging Manual) treated by the senior author during 2006–2018. Patients were grouped into those who were treated before February 2012 (“before vismodegib approval”) and those who presented later (“after vismodegib approval”). Results: Forty-two patients with locally advanced periocular BCC were treated during the study period, of whom 31 were men. The median age at presentation was 66 years (range, 43–90). Twenty-two patients had T4a and 20 had T4b tumors. Thirteen patients were treated before and 29 were treated after vismodegib approval. The 2 groups did not differ in age distribution (p = 0.164), sex distribution (p = 0.270), prevalence of recurrent tumor at presentation (p = 0.317), or duration of treatment with vismodegib (p = 0.605). Orbital exenteration was significantly more prevalent in patients treated before vismodegib approval than after (46% vs. 10%, p = 0.016), and vismodegib treatment was significantly more prevalent in patients treated after vismodegib approval than before (when vismodegib was given in clinical trials; 69% vs. 23%, p = 0.008). There was a trend toward more patients retaining their eyes at last follow-up in patients treated after vismodegib approval (83% vs. 54%, p = 0.066). Conclusions: The prevalence of orbital exenteration as a necessary surgical procedure in patients with a locally advanced periocular BCC has fallen since the Food and Drug Administration approval of vismodegib. Although vismodegib is not specifically approved for organ-sparing, it has changed the authors’ practice and enabled eye preservation in patients with locally advanced periocular BCC, who would otherwise require an orbital exenteration.

Outcomes of orbital exenteration for craniofacial lesions

“…The majority of cases are performed for life‐threatening malignancy of the periorbital skin, paranasal sinuses, or skull base. With the introduction of orbital‐preservation techniques, the indications for radical orbital excision have diminished, with increasing favor for preserving the involved eye over aggressive resection 4‐11,24‐28 . In 1994, Paridaens et al 29 argued that OE should be reserved as a palliative procedure for late disease stages.…”

“…More recently, histology and the extent of local invasion have been included in management algorithms to better identify OE candidates 31 . In particular, these show a role for OE in patients with well‐differentiated tumors with massive orbital content involvement or for high‐grade tumors that are not responsive to biologic therapies or chemotherapies 5,23,32 . Similarly, combined craniofacial resection techniques are considered standard of care for invasive malignant tumors of the paranasal sinuses 33‐35 …”

“…In more recent years, multidisciplinary eye‐sparing approaches using a combination of eye‐sparing surgery and subsequent adjuvant radiation therapy or concurrent chemoradiation in the case of lacrimal gland carcinoma and biologic therapy and immunotherapy in the case of cutaneous cancers have also demonstrated efficacy. Furthermore, several reports have shown that OE may not be necessary to improve survival for early‐stage disease 5‐11 . In addition, neoadjuvant chemotherapy for sinonasal cancers may be used for cytoreduction, and in patients with a significant response to chemotherapy, orbital preservation is feasible without compromising the oncologic outcome for select patients 12,13 .…”

Outcomes of adjunctive therapies post hedgehog inhibitors in the management of locally advanced basal cell carcinoma: A systematic review and pooled analysis

“…13,14,[17][18][19][20]23,25,27,28,31,41,42,47 Following HHIT, 12 studies (40/49 or 81.6% of lesions; 16 orbital/ periocular and 24 head/neck, trunk, or extremity) specifically reported an overall reduction of the expected and/or actual surgical defect area. 13,14,[17][18][19][20]23,25,27,28,31,41,42,47 Eighteen lesions were treated with MMS, while 22 underwent surgical resection. Ally et al 14…”

Letter to the editor: Effective treatment of locally advanced periocular basal cell carcinoma with oral hedgehog pathway inhibitor

“…Surgical treatment of a locally advanced BCC would require orbital exenteration or surgery, resulting in defects that would be impossible to repair without loss of eye function or significant facial disfigurement. The HPIs are recommended for periocular locally advanced or metastatic basal cell carcinoma (BCC) to avoid exenteration [2].…”