Over the past decade, immunotherapy has demonstrated an impressive improvement in treatment outcomes for multiple cancers. Following the landmark approvals for use of immune checkpoint inhibitors, new challenges emerged in various clinical settings. Not all tumor types harbor immunogenic characteristics capable of triggering responses. Similarly, many tumors’ immune microenvironment allows them to become evasive, leading to resistance and, thus, limiting the durability of responses. To overcome this limitation, new T-cell redirecting strategies such as bispecific T-cell engager (BiTE) have become attractive and promising immunotherapies. Our review provides a comprehensive perspective of the current evidence of BiTE therapies in solid tumors. Considering that immunotherapy has shown modest results in advanced prostate cancer to date, we review the biologic rationale and promising results of BiTE therapy in this clinical setting and discuss potential tumor-associated antigens that may be integrated into BiTE construct designs. Our review also aims to evaluate the advances of BiTE therapies in prostate cancer, illustrate the major obstacles and underlying limitations, and discuss directions for future research.

This study’s purpose was to assess symptom cluster (SC) stability during disease progression and determine their strength of association with survival in patients with advanced cancer . Consecutively eligible patients with advanced cancer not receiving cancer-specific treatment and referred to a Tertiary Palliative Care Clinic were enrolled in a prospective cohort study. At first consultation (D₀) and in subsequent consultations at day 15 (D₁₅) and day 30 (D₃₀), patients rated 9 symptoms through the Edmonton Symptom Assessment System scale (0-10) and 10 others using a Likert scale (1-5). Principal components factor analysis with varimax rotation was used to determine SCs at each consultation. Of 318 patients with advanced cancer, 301 met eligibility criteria with a median age of 69 years (range 37-94). Three SCs were identified: neuro-psycho-metabolic (NPM), gastrointestinal, and sleep impairment, with some variations in their constitution over time. Exploratory factor analysis accounted for 40% of variance of observed variables in all SCs. Shorter median survival was observed continuously for NPM cluster (D₀ 23 vs. 58 days, P < .001; D₁₅ 41 vs. 104 days, P=.004; D₃₀ 46 vs. 114 days, P = .002), although the presence of 2 or more SCs on D₀ and D₁₅ also had prognostic significance (D₀: 21 vs. 45 days, P = .005; D₃₀: 50 vs. 96 days, P = .040). In a multivariable model, NPM cluster (D₀ hazard ratio estimate: HR 1.64; 95%CI, 1.17-2.31; P = .005; D₁₅ HR: 2.51; 95%CI, 1.25-5.05; P = .009; D₃₀ HR: 3.9; 95%CI, 1.54-9.86; P = .004) and hospitalization (D₀ HR: 2.27; 95%CI, 1.47-3.51; P < .001; D₁₅ HR: 2.43; 95%CI, 1.18-5.01; P = .016; D₃₀ HR: 3.41; 95%CI, 1.35-8.62; P = .009) were independently and significantly associated with worse survival. Three clinically relevant SCs were identified, and their constitution had small variations, maintaining a stable set of nuclear symptoms through disease progression. Presence of the NPM cluster and hospitalization maintained their prognostic value over time.

One year ago, Portugal entered its first lockdown because of the coronavirus disease-2019 (COVID-19) pandemic. The impact of this on delays in cancer diagnosis and treatment is a major concern, which may negatively affect the outcomes of these patients. This retrospective, single-center analysis compared the clinical and pathological characteristics of breast cancer (BC) patients referred to a medical oncology first appointment between March 2020 and 2021, with the same period in the previous year. Strikingly, there was a 40% reduction in the number of BC patients during lockdown. However, there was a statistically significant increase in the proportion of metastatic BC patients admitted for the first time for systemic therapy (13.6% vs. 28.9%, p = 0.003). Additionally, a statistically significant increase in the number of patients with bilateral early BC at diagnosis after March 2020 was found (7.2% vs. 1.9%, p = 0.043). These findings support international recommendations for an accelerated restoration of BC screening, to reduce incidence of advanced breast cancer at diagnosis and mitigate the expected impact of the COVID-19 pandemic on patients with cancer. Further work is needed to examine in detail the impact of measures to manage the COVID-19 pandemic on breast cancer outcomes.

353 Background: ICI were approved for advanced RCC treatment either alone or combined with another ICI or a tyrosine kinase inhibitor. While most trial data derive from clear cell (cc) histology, the differential activity of ICI in nccRCC subtypes is not entirely known. The aim of this analysis is to summarize the reported activity of ICI-based therapies in ncc-subtypes or in tumors with sarcomatoid/rhabdoid features. Methods: A systematic literature search following PRISMA guidelines was performed. PubMed, GoogleScholars and ASCO Database were searched for the key-words “renal cell cancer” and “immune check point inhibitors” and equivalents. Publications between July 2016 - July 2021 were considered. All original articles reporting outcomes of ICI in at least 5 patients with an advanced nccRCC were eligible. Case reports, reviews, out of scope publications and articles with no full text available were excluded. Results: This study included a total of 14 publications, mostly case series except one phase II and one phase IIIb/IV trial. The table below summarizes the different histological subtypes included in these studies, more frequently papillary (10-88%), chromophobe (0-34%) and unclassified (4-27.5%) RCC. As for first line (L), ICI monotherapy elicited an overall response ratio (ORR) of 5-26.7%, a median progression free survival (mPFS) of 2.2-4.2 months (m) and a median overall survival (mOS) of 16.3-28.9m. ICI combination therapy associated with a higher ORR of 14.2-33%, a mPFS of 2.4-8.3m and a mOS not reached (NR). In ≥2^ndL, ICI alone elicited an ORR of 9.4-22.6%, a mPFS of 3.5-7.1m and a mOS of 11.6m-NR. ICI combination therapy was superior, with a reported ORR of 31-44.4%, a mPFS of 4.3-5.6m and a mOS NR. Overall, ICI therapy elicited a higher ORR in papillary tumors (5-50%). Unclassified RCC response was more variable (0-66.7%). Chromophobe tumors had a lower ORR of 0-20%. ICI therapy outcomes among nccRCC with sarcomatoid/rhabdoid features were of an ORR of 0-42.1%, a mPFS of 2.3-6.9m and a mOS of 25.5m–NR. Nonetheless, outcomes were inferior in ncc comparing to cc tumors. Conclusions: The observed activity of ICI-based therapies was heterogenous among nccRCC subtypes. Combination regimens, papillary subtype and sarcomatoid/rhabdoid features were associated with higher responses. These findings might help treatment decisions and require further validation.[Table: see text]

Male Breast Cancer in Portugal: A Descriptive Analysis of a 20-Year Cohort - European Journal of Breast Health

Autops Case Rep, vol.10, n3, e2020179, 2020