Sacituzumab Govitecan for the treatment of advanced triple negative breast cancer patients: a multi-center real-world analysis.

Objective: The objective of this multicenter, observational, retrospective analysis was to evaluate the safety and efficacy of sacituzumab govitecan in metastatic triple-negative breast cancer (mTNBC) patients managed according to common clinical practice in Italy. Methods: Data were retrieved by 7 sites. Triple-negative BC was defined by the lack of expression of estrogen receptor (ER <1%), progesterone receptor (PgR <1%) and human-epidermal growth factor receptor-2 (HER2 0, 1+, 2+ ISH-not amplified) according to standard ASCO-CAP criteria. Demographic and clinical characteristics were collected. Premedication, dose modifications and treatment schedule were based on the approved label of the product. Adverse events (AEs) were assessed according to NCI-CTCAE v5.0. Results: Fifty-seven eligible patients who received sacituzumab govitecan for mTNBC were included. Median age was 53 years (range 25-75). Approximately 70% of patients had an initial diagnosis of TNBC. Median time from the diagnosis of metastatic BC to start of sacituzumab govitecan was 17 months (range 0-97) and median number of previous therapies was 3 (range 1-7). The most common sites of metastasis were lymph nodes (63.1% of patients), lung (57.9%), bone (50.8%) and liver (38.6%). Eight (14.0%) patients had a disease-free interval ≤12 months. A total of 32 (56.1%) deaths were observed and the median overall survival (OS) was 12.43 months (95% CI, 7.97 months-not reached). At a median follow-up of 10.6 months, 45 patients (78.9%) had progression and the median progression-free survival (PFS) was 4.9 months (95% CI, 3.7-7.1 months). Partial tumour response was observed in 19 patients (33.3%), stable disease in 16 (28.1%) and disease progression in 22 patients (38.6%). The most common treatment-related AEs were anemia (66.6% of patients), alopecia (66.6%), neutropenia (59.6%), nausea (42.1%) and diarrhea (38.6%). Neutropenia was the most common serious treatment-related AE: 21.0% and 8.7% of patients experienced grade 3 or 4 neutropenia, respectively. Twenty-two patients (38.6%) reduced the dose and 5.3% permanently discontinued treatment. Conclusion: The results of this real-world analysis showed that both safety and efficacy of sacituzumab govitecan in mTNBC patients are consistent with that previously reported in regulatory trials. The use of premedication and supportive measures was associated with a satisfactory toxicity profile.

Look at This Swelling: Retroauricular Mass as Atypical Progression in Long-Survivor Endometrial Endometrioid Adenocarcinoma.

Endometrial endometrioid adenocarcinoma is the most common histology in gynecological malignancies. Most women present loco-regional relapsing or peritoneal and liver involvement within three years from diagnosis. However long-survivor patients may be affected by atypical disease evolutions. Here we describe an extremely rare case of retroauricular metastasis in a patient affected by endometrial endometrioid adenocarcinoma, who had a total abdominal hysterectomy and bilateral salpingo-oophorectomy six years earlier and subsequent salvage surgery three years later for loco-regional relapsed disease.

Combination of immunotherapy, radiotherapy and denosumab as the best approach even for NSCLC poor prognosis patients: a case report with strong response, prolonged survival and a review of literature.

Non-Small Cell Lung Cancer (NSCLC) with bone metastasis and poor performance status has the worst prognosis even in strong PD-L1 expression patients. Treatment approach includes immuno- or chemo-immunotherapy, Radiotherapy (RT) and Bone-Targeted Therapy (BTT) but there is insufficient data to suggest the best time to use each of them, alone or in combination. Using an integrated and synergistic treatment strategy with immunotherapy, radiotherapy, and Denosumab as BTT is probably the best treatment planning for metastatic NSCLC for both good and poor performance status patients, although more data are needed to confirm this approach. Here we describe an interesting case report on patient with extensive bone involvement from NSCLC and PS >2 treated simultaneously with radiotherapy, immunotherapy and BTT, achieving an excellent clinical benefit, radiological and metabolic complete response, as a sort of Lazarus effect. We analyzed our result comparing with currently published data about radio-immunotherapy or immunotherapy and BTT combination even though there is no published experience about integration of all 3 treatments. Approval studies often do not represent real-world experience (RWE), so we analyzed data from both RWE and clinical trials.

HER2-Low Status Does Not Affect Survival Outcomes of Patients with Metastatic Breast Cancer (MBC) Undergoing First-Line Treatment with Endocrine Therapy plus Palbociclib: Results of a Multicenter, Retrospective Cohort Study.

BACKGROUND: Approximately 45-50% of breast cancers (BCs) have a HER2 immunohistochemical score of 1+ or 2+ with negative in situ hybridization, defining the "HER2-low BC" subtype. No anti-HER2 agents are currently approved for this subgroup in Europe, where treatment is still determined by HR expression status. In this study, we investigated the prognostic significance of HER2-low status in HR+/HER2- metastatic BC (MBC) patients treated with endocrine therapy (ET) plus palbociclib as first line. METHODS: We conducted a retrospective study including 252 consecutive HR+/HER2- MBC patients who received first-line ET plus palbociclib at six Italian Oncology Units between March 2016 and June 2021. The chi-square test was used to assess differences in the distribution of clinical and pathological variables between the HER-0 and HER2-low subgroups. Survival outcomes, progression-free survival (PFS) and overall survival (OS), were calculated by the Kaplan-Meier method, and the log-rank test was performed to estimate the differences between the curves. RESULTS: A total of 165 patients were included in the analysis: 94 (57%) and 71 (43%) patients had HER2-0 and HER2-low disease, respectively. The median age at treatment start was 64 years. No correlation between patients and tumor characteristics and HER2 status was found. Median PFS (mPFS) for the entire study cohort was 20 months (95% CI,18-25 months), while median OS (mOS) was not reached at the time of analysis. No statistically significant differences, in terms of PFS (p = 0.20) and OS (p = 0.1), were observed between HER2-low and HER2-0 subgroups. CONCLUSIONS: In our analysis, HR+ MBC patients with low HER2 expression who received first-line treatment with ET plus Palbociclib reported no statistically different survival outcomes compared to HER2-0 patients. Further prospective studies are needed to confirm the clinical role of HER2 expression level.

First-line Treatment of Advanced Biliary Ducts Carcinoma: A Randomized Phase II Study Evaluating 5-FU/LV Plus Oxaliplatin (Folfox 4) Versus 5-FU/LV (de Gramont Regimen).

BACKGROUND/AIM: Few clinical trials are available for advanced biliary tract carcinoma (BTC). We conducted this randomized phase II clinical trial to explore efficacy and safety of 5-fluorouracil/leucovorin (5-FU/LV - de Gramont) or the same regimen plus oxaliplatin (Folfox 4) as first-line treatment of advanced BTC. PATIENTS AND METHODS: Primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), response and toxicity. RESULTS: A total of 48 patients were enrolled, 23 in de Gramont arm and 25 in the Folfox arm. Disease control rate was 56.5% for de Gramont vs. 72% for Folfox. RR was 21.7% for de Gramont arm and 28% for Folfox arm (p=0.12). PFS was in favor of Folfox (5.2 vs. 2.8 months; p=0.031). OS was 7.5 and 13.0 months for de Gramont and Folfox arm respectively (p=0.0010). Toxicity was generally mild in both arms. CONCLUSION: Folfox 4 could be considered a valid option as first-line treatment of BTC due to its efficacy and tolerability.

Primary Leiomyosarcoma of the Great Saphenous Vein: Case Report and Review of the Literature.

Soft tissue sarcomas are very rare tumors, representing less than 1% of all cancers. Leiomyosarcomas are a rare group of them representing about 6% of soft tissue sarcomas and they involve smooth muscles. Less than 2% of all leiomyosarcomas involves large blood vessels. Leiomyosarcomas of vein tunica media are very rare (1/100,000 malignant cancers) and only 10% of these originate from the great saphenous vein. In this article, we report a clinical case that occurred in our institution and review all the literature available at now.

Long-term survival in small cell lung cancer: a case report and review of the literature.

Small cell lung cancer (SCLC) represents approximately 13% of all newly diagnosed lung cancers. SCLC is a very aggressive disease characterized by early locoregional and distant metastases. The median survival is 14-16 months for patients with limited disease and 8-11 months for those with extensive disease, with 20-40% of patients with limited disease and 5% of patients with extensive disease alive at 2 years. This report discusses the case of a long-term SCLC survivor treated with radiotherapy, several lines of chemotherapy and long-acting somatostatin analogs who is alive 7 years after diagnosis, with no evidence of further relapse. In the near future, better identification of prognostic and predictive factors based on models that integrate clinical data and multiple gene expression profiles and the use of novel treatments could increase the number of long-term SCLC survivors.

Anal metastasis from breast cancer: a case report and review of the literature.

Breast cancer usually metastasizes towards the lymph nodes, lung, bone, liver or brain; metastatic gastrointestinal involvement is rare and anal metastases are extremely rare. Necroscopic studies report a 6-18% incidence of extra-hepatic gastrointestinal metastases, and the most frequent sites of the GI tract involved are the stomach and the small intestine. We report a case with anal metastasis from breast cancer and a review of the associated literature.

Adjuvant chemotherapy in resected non-small cell lung cancer.

There is still a high mortality ratio in completely resected non-small cell lung cancer patients either due to local or, more often, to metastatic recurrence. The NSCLC Collaborative Group Meta-analysis demonstrated a not statistically significant advantage in patients treated with cisplatin-based regimens. Many subsequent trials were unable to demonstrate the real effectiveness of cisplatin-based adjuvant chemotherapy with a significant rate of toxicity. The IALT trial demonstrated little advantage in overall and disease-free survival with acceptable toxicity. A recent meta-analysis of trials including 5716 patients demonstrated the role of cisplatin-based chemotherapy as adjuvant treatment of resected non-small cell lung cancer even if results shoud be carefully examined. At present, adjuvant chemotherapy in non-small cell cancer should not be reserved to experimental trials.

Dystroglycan expression is frequently reduced in human breast and colon cancers and is associated with tumor progression.

Dystroglycan (DG) is an adhesion molecule responsible for crucial interactions between extracellular matrix and cytoplasmic compartment. It is formed by two subunits, alpha-DG (extracellular) and beta-DG (transmembrane), that bind to laminin in the matrix and dystrophin in the cytoskeleton, respectively. In this study we evaluated by Western blot analysis the expression of DG in a series of human cancer cell lines of various histogenetic origin and in a series of human primary colon and breast cancers. Decreased expression of DG was observed in most of the cell lines and in both types of tumors and correlated with higher tumor grade and stage. Analysis of the mRNA levels suggested that expression of DG protein is likely regulated at a posttranscriptional level. Evaluation of alpha-DG expression by immunostaining in a series of archival cases of primary breast carcinomas confirmed that alpha-DG expression is lost in a significant fraction of tumors (66%). Loss of DG staining correlated with higher tumor stage (P = 0.022), positivity for p53 (P = 0.033), and high proliferation index (P = 0.045). A significant correlation was also observed between loss of alpha-DG and overall survival (P = 0.013 by log-rank test) in an univariate analysis. These data indicate that DG expression is frequently lost in human malignancies and suggest that this glycoprotein might play an important role in human tumor development and progression.