Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer in white-skinned populations. Advanced or metastatic disease is rare, less than 5% of patients (pts), but when it occurs, is difficult to treat and often has a poor prognosis. Immune checkpoint blockade with cemiplimab, a PD-1 inhibitor, has been approved for advanced/metastatic CSCC1 were is getting excellent results.2 However, unlike what is already standard pratice for melanoma skin cancer,3 4 we do not know yet which is the optimal treatment duration. The aim of this study is to evaluate the minimum treatment period with cemiplimab in order to guarantee a durable clinical benefit.
Methods
In this retrospective study was evaluated the duration standard treatment with cemiplimab 350 mg every 3 weeks (Q3W) in 95 pts with CSCC, on which 22 were discontinued not by clinical decision (figure 1). Demographic and clinical data were tabulated using descriptive statistics. PFS was calculated as the time from randomization until objective tumor progression or death, whichever occurs first; OS was calculated from randomization until death by any cause.
Results
Overall, 95 pts were enrolled. Demographic and clinical characteristics are reported in table 1. The median age was 75 years (range, 32–96 years), and 68 (72%) pts were males. Cemiplimab was administered as first-line therapy in 45 (47%) pts and as second-line in 50 (53%) subjects; The most frequent comorbidities were blood hypertension (51%) and angina/coronary artery disease (23%). At the first follow-up visit, 10 (11%) pts achieved CR, 25 (26%) PR, 35 (37%) reached SD, and 25 (35%) were in progression. Twenty-two stopped cemiplimab treatment due to comorbidity (n=7), toxicity (n=3), no compliant (n=9) and complete response (n=3). No significant difference was observed in this cohort compared to general population (figure 2) in terms of OS (p=0.47; HR 0.80 (95% CI 0.42 to 1.48)) and PFS (p=0.29; HR 0.72 (95% CI 0.39 to 0.32). In the swimmer plot cartoon (figure 3), we observed 10 death events in pts treated for less than a year (n=12), only 1 death in pts treated at least 1 year (n=10) and 0 death in pts treated at least 2 years (n=5) (figure 4).
Conclusions
From a patients, healthcare, and economic perspective, shorter treatment duration is preferred, and overtreatment should be prevented. In these preliminary result we showed that at least one year of treatment with cemiplimab appears to be a valid option. Further investigations are needed to get additional information.
References
Goodman DT. Cemiplimab and Cutaneous Squamous Cell Carcinoma: From Bench to Bedside. JPRAS Open. 2022 Jun 23;33:155−160. doi: 10.1016/j.jpra.2022.06.003. Baggi A, Quaglino P, Rubatto M, Depenni R, Guida M, et al. Real world data of cemiplimab in locally advanced and metastatic cutaneous squamous cell carcinoma. Eur J Cancer. 2021 Nov;157:250−258. doi: 10.1016/j.ejca.2021.08.018. Mulder EEAP, de Joode K, Litière S, Ten Tije AJ, Suijkerbuijk KPM, et al. Early discontinuation of PD-1 blockade upon achieving a complete or partial response in patients with advanced melanoma: the multicentre prospective Safe Stop trial. BMC Cancer. 2021 Mar 25;21(1):323. doi: 10.1186/s12885-021-08018-w. Coen O, Corrie P, Marshall H, Plummer R, Ottensmeier C,et al. The DANTE trial protocol: a randomised phase III trial to evaluate the Duration of ANti-PD-1 monoclonal antibody Treatment in patients with metastatic mElanoma. BMC Cancer. 2021 Jul 1;21(1):761. doi: 10.1186/s12885-021-08509-w.
Ethics Approval
This study was approved by the Ethics Committee of National Cancer Institute—IRCCS—Fondazione ''G. Pascale'', Naples, Italy, protocol number 32/22 oss. All patients provided their written informed consent to participate in this study.
Consent
Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal
Abstract Background Prognostic factors for initial response of advanced cutaneous squamous cell carcinoma to cemiplimab treatment are lacking. Il-6 has been found to affect immune cell populations which impact tumor development. The aim was to investigate the prognostic significance of IL-6 serum levels before and during treatment. Methods Serum levels of IL-6 were correlated with clinical outcomes in a retrospective study. Results Overall, 39 patients were enrolled. High serum levels of IL-6 (> 5.6 pg/ml) were associated with poorer survival (45.1% vs 0 deaths; OS: 16.1 ± 1.5 vs 20.8 ± 0 months, 95% CI 13,046 to 19,184) and shorter PFS (10.3 ± 1.9 vs 18.9 ± 1.5 months; 95% CI 3433 to 10,133) in patients with advanced CSCC treated with cemiplimab. In addition, patients whose IL-6 level increased after treatment with cemiplimab, independently of the basal level, had a poorer response to treatment than patients whose level was reduced or stable after immunotherapy. Conclusions Serum levels of IL-6 at baseline and changes after cemiplimab immunotherapy may have a prognostic significance in patients with advanced cutaneous squamous cell carcinoma.
e20112 Background: The rarity and the unpredictable natural history of thymic tumors (TTs), make their management a real challenge for clinicians. Here, we describe the clinic-pathological features and clinical outcomes of seven cases of advanced heavily pretreated TTs, which responded to oral etoposide, after progressed to biological agents. Methods: Seven patients, referred to our Centre for a period of nine years, were included in this monocentric retrospective study. With a median age of 48 years (36-78), all patients (3 women and 4 men) had a diagnosis of advanced disease. According to Masaoka-Koga stage system, five patients had IVB stage disease, the other two, respectively, had III and IVA stage. Radical thymectomy was performed in III stage patient, who progressed after six months. According to WHO 2004 classification histological diagnosis of thymoma was made in five pts (B2/B3 2 pts; B3 2 pts; B2 1 pt). Thymic carcinoma (TC) was diagnosed in the last two patients. A first line platinum plus anthracycline chemotherapy was administrated. After progressed to chemotherapy, all patients started treatment with biological agents. Specifically, two patients OctreoScan positive, underwent long acting somatostatin analogues (Octreotide Lar 30 mg/4 weeks) plus prednisone (0.2 mg/kg), while five patients, in a compassionate setting, started Everolimus (10 mg/daily). After progression documented by a CT scan, all of them received oral etoposide at dose of 50 mg daily three week on/ one week off. Overall response rate and toxicities were evaluated. Results: Partial response, according to RECIST criteria 1.1., was achieved in five patients (72%). Two patients with TC progressed after at least 3 cycles of therapy. G1 Nausea was registered in 3 cases, no hematological toxicity has been detected. Four patients are still on treatment with no relevant toxicities with a median of 12 cycles. One patient died owing to complication of surgery for acute abdomen. Conclusions: Our experience of long lasting management of advanced relapsed TET, shows as the histological diagnosis could help clinicians for the best therapeutic choice. Oral etoposide is a well tolerated and effective cytotoxic agent. Further studies are needed.
Background The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region. Methods This survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2–positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher’s exact tests for dichotomous answers and χ 2 test for trends relative to the questions with 3 or more options. Results This is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2–positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients’ planned treatment approach). The results from responders in Campania did not differ significantly from the national ones. Conclusion Our study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts.
Background
Thymic hyperplasia is a rare differential diagnosis of anterior mediastinal lesions. Histological and radiological criteria are used to distinguish this benign condition from other malignant diseases; it is often associated with Myasthenia gravis. Here we report our monocentric experience of five patients, affected by advanced thymic epithelial tumors (TETs), with a previous diagnosis of thymic hyperplasia.
e20648 Background: Thymic epithelial tumors (TETs) are extremely rare and heterogenous neoplasms, associated with immune dysregulation. Recognized prognostic factors are TNM stage and the Masaoka-Koga classification. To the best of our knowledge, no study has been conducted to investigate the correlation between immunophenotype, level of cytokines, chemochines and clinical outcome in TETs patients. The aim of this study was to evaluate the correlation of immunological signature and long-term outcome in patients with TETs and Good Syndrome (GS). Methods: From May 2019 to October 2022, consecutive patients with TETs and GS, referred to the Rare Tumors Coordinating Center of Campania Region (CRCTR) of Federico II of Naples, were enrolled. The immunophenotype of monocytes, neutrophils, eosinophils, CD4+ T cells, CD8 + T cells, B-cells, NK cells and NKT-cells, T regulatory cells, and the evaluation of serum levels of cytokines, chemokines and growth factors were assessed using the 8-color immunophenotyping kit, Treg detection kit and pre-formed Kits by Bioplex multiplex, respectively. D’Agostino-Pearson normality test was used to evaluate whether the continuous data were normally distributed, and a two-tailed t-test for independent samples was used. Overall survival (OS) analysis was performed generating Kaplan-Meier curves and Cox Univariate models for the considered categorical stratifications. p-values < 0.05 were considered statistically significant. Results: A total of 24 consecutive TETs patients were included in the study: 13 (54.17%) patients were male and 11 (48.83%) were female, with a median age of 54.96 ± 9.6 years. Tumor histology included 20 thymoma, and 4 thymic carcinoma. Autoimmune diseases were found in 13 patients all of whom had thymoma. At the time of this analysis, 5 (20.83%) patients had no evidence of disease (NED) by imaging and were in follow-up, 17 (70.83%) patients were still alive. The analysis of leucocytes did not show statistically significant association with clinical outcome of TETs patients. On the contrary, a statistically significant correlation between serum concentration of IL-6 and OS was found with lower levels of IL-6 associated with poorer prognosis (HR: 9.654; p = 0.016). In addition, we found a statistically significant reduction of IL-2 (p = 0.04), IL-15 (p = 0.048), IL-5 (p = 0.03) and VEGF (p = 0.01) serum levels in patients with evidence of disease, as compared to NED patients. Conclusions: Overall, these findings suggest that measurement of IL-6 levels may be a useful parameter for identifying TETs patients with GS who have more aggressive diseases. Our preliminary data may be useful in the clinical management of this complex disease. Further studies are needed to better understand the pathophysiology and clinical implications of immunophenotype alterations in TETs patients.
e20111 Background: Thymic carcinoma (TC), as largely known, has more aggressive behaviour than thymoma. Usually, patients affected by TC received at the beginning, a diagnosis of advanced disease, which is inoperable in around half of the cases. Among those who underwent a total resection, more than half presented a recurrence. Furthermore, the 5-year survival rate is significantly different between TC (50.5%) and thymoma patients (94.4%). Methods: In this retrospective monocentric study, we presented the clinical-pathological features of 20 consecutive patients referred to our centre of Rare tumors from January 2008 to December 2014. All of them, with a median age of 55 years (33-78) and a female/male ratio of 0.53 (7 F and 13 M), received an histological diagnosis of TC revised by central review. A radical surgery was performed only in 5 cases, all the pts had an advanced disease at diagnosis, IVB stage disease according to Masaoka-Koga stage system was detected in 14 pts, IVA and III in 4 and 2 pts, respectively. They all underwent first line platinum based chemotherapy, most of them progressed very soon and several biological agents were administrated for control disease. We evaluated time to progression (TTP) of six pts who subsequently were treated with platinum chemotherapy; long acting somatostatin analogues (LAR octreotide 30 mg/4 weeks) plus prednisone (0.2mg/Kg); everolimus (10 mg/daily). Also Median overall survival of this series was calculated. Results: Six patients treated in a multimodality way, had a IVB stage disease. Considering the sequence of chemotherapy, somatostatin analogues plus prednisone and everolimus, they reached a TTP of 4, 13 and 5.5 months, respectively. Median Overall survival of all 20 pts was 28 months (5-180). Conclusions: Advanced Thymic carcinoma should be managed in a multimodality setting with individualized treatment, according to improved biological and histological informations/new biomarkers that are still missing. Functional imaging like OctreoScan and 18FDG/PET should help clinicians for the best choice also in thymic carcinoma treatment.
7581 Background: Thymic epithelial tumors are rare neoplasms with a particular biological behavior, treated with a combination of therapeutic strategies such as surgery, chemotherapy, radiotherapy and target agents. No continuation maintenance therapy exists for these rare tumors. An high uptake of indium-labeled octreotide (111In-DTPA-D-Phe1-octreotide) and curative application of somatostatin analogs in thymic tumors have been widely demonstrated. Methods: Eighteen patients (nine women and nine men, median age 54.5 years; range 32-78) with advanced thymic tumors (seven patients with stage III; seven with IVa; Four with IVb according to the Masaoka-Koga staging system), histotype sec WHO revised by central review (three AB, two B1, three B2, five B3, three B2/B3, two thymic carcinoma) with a partial response or stable disease to conventional chemotherapeutic regimens platinum or not platinum-based, after performed OctreoScan, were enrolled in this monocentric referral center study. The schedule includes administration of long-acting analog octreotide (30 mg/every 28 days intramuscularly), until progression of disease was documented. Median time to progression and toxicity were evaluated. Results: Median follow-up was of 43 months with a median time to progression of 14,5 months (range 77-2). Treatment was generally well tolerated with acceptable toxicity: Grade 1 diarrhea (5 patients), Grade 2 hyperglycemia (4 patients). No patients interrupted treatment because of toxicity. Conclusions: The current study indicates that single-agent somatostatin analogs maintenance therapy is a potential treatment strategy for advanced TETs OctreoScan positive which responde to previous conventional chemotherapy. In particular, somatostatin analogs may provide an effective maintenance treatment duration regardless of histotype and stage of disease with an acceptable toxicity and an improved patients’compliance.
