Targeted Therapeutic Approaches in Vulvar Squamous Cell Cancer (VSCC): Case Series and Review of the Literature

Abstract

Therapeutic options in recurrent or metastasized VSCC not amenable to radiotherapy or radical surgery are limited. Evidence for the use of targeted therapies is sparse. All patients with VSCC treated at the Gynecological Cancer Center Hamburg-Eppendorf 2013 - 2019 were retrospectively evaluated for targeted therapeutic approaches. Furthermore, a MEDLINE, EMBASE-, Web of Science-, Scopus- and OVID database search was performed using the terms: ‘vulvar cancer’ AND ‘targeted therapy’, ‘erlotinib’, ‘EGFR’, ‘bevacizumab’, ‘VEGF’, ‘pembrolizumab or ‘immunotherapy’. 12/291 patients (4.1%) with VSCC received at least one targeted therapy at our institution. Previously, one or more platinum-based chemotherapy was applied to all patients (median 3.5 previous lines (range 2-5). In the erlotinib subgroup 2/5 patients (40%) achieved stable disease (SD) while two patients (2/5, 40%) experienced partial response (PR). Treatment was given as monotherapy in 2nd/3rd line for a median of 3.4 months (range 2-6 months). Bevacizumab (n=9) was given as maintenance therapy after platinum-based first-line chemotherapy (9/9), best response was complete response (CR) (n=2/9 22.2%). Median duration of treatment was 7 months (range 4-13 months) with two patients still under ongoing treatment. Best response in the pembrolizumab (n=3) subset was SD (n=1/3 33%). Treatment was given as monotherapy in 2nd/3rd line for a median of 3.3 months (range 3-4 months). 9/12 patients (75%) experienced treatment-related AEs (TRAEs), most commonly grade 1/2. Rapidly evolving antibody treatments have proven clinical benefit especially in HPV-driven tumor entities, however, clinical investigations in VSCC are still limited. These reported cases provide evidence for the clinical utility and feasibility while ensuring an acceptable safety profile.

Immunotherapy for recurrent or metastatic vulvar carcinoma: A case report and review of current guidelines

“…HPV-associated VSCC is characterized by p16 overexpression, mostly arises in younger patients (aged 30–50 years) and has a better overall survival (OS) and longer disease-free survival (DFS) when compared to HPV-independent VSCC. However, HPV-associated VSCC accounts for only up to 40% of VSCC ( Borella et al, 2021 , Kortekaas et al, 2021 , Woelber et al, 2021 ). The majority of VSCC cases are HPV-independent, often harbor TP53 mutations and typically present in post-menopausal patients.…”

“…Treatment and prognosis for VSCC depend on the tumor stage at initial diagnosis (3-year progression-free survival [PFS] rate of 35.2% and OS rate of 56.2% in patients with node-positive disease, compared to 75.2% and 90.2%, respectively, in those with node-negative disease) ( Borella et al, 2021 , Woelber et al, 2021 ). Treatment for early-stage disease consists of radical surgery.…”

“…Therapeutic options are extremely limited for locally advanced, recurrent, or metastatic disease not amenable to radiotherapy and/or radical surgery. There is poor prognosis in the metastatic setting, as reflected by a one-year survival of 15–30% ( Woelber et al, 2021 ). Given the poor response rates to second-line chemotherapy after initial platinum-based regimens and the presence of frequent comorbidities in older patients, there is a clear need for new and less toxic therapeutic options ( Borella et al, 2021 , Han et al, 2012 , Witteveen et al, 2009 ).…”

Perineural Invasion in Vulvar Squamous-Cell Carcinoma Is an Independent Risk Factor for Cancer-Specific Survival, but Not for Locoregional Recurrence: Results from a Single Tertiary Referral Center

“…Additionally, with the rapid development of precision medicine for VC [ 59 , 60 , 61 ], basic and translational research is needed in order to better understand the mechanisms underlying PNI, so as to identify possible therapeutic targets [ 36 ].…”

Role of Chemotherapy in Vulvar Cancers: Time to Rethink Standard of Care?

“…In a case series recently published, targeted agents were given as second-third lines in cisplatin pretreated patients, reporting complete responses in two out of nine patients treated with bevacizumab, and partial responses in two out of five patients treated with erlotinib [74]. The use of immunotherapy, alone or in combination with chemotherapy, is an emerging and evolving field of research in vulvar carcinoma, opening a new scenario in this rare tumor, although the inherent data are still limited [75].…”