Background: Duligotuzumab, a novel dual-action humanized IgG1 antibody that blocks ligand binding to EGFR and HER3, inhibits signaling from all ligand-dependent HER dimers, and can elicit antibody dependent cell mediated cytotoxicity. High tumor-expression of neuregulin 1 (NRG1), a ligand to HER3, may enhance sensitivity to duligotuzumab. Methods: This multicenter, open-label, randomized phase II study (MEGHAN) evaluated drug efficacy in patients with recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) progressive on/after chemotherapy, and among patients with NRG1-high tumors. Patients received duligotuzumab (1100 mg IV, q2w) or cetuximab (400 mg/m2 load, 250 mg/m2 IV, q1w) until progression or intolerable toxicity. Tumor samples were assayed for biomarkers (NRG1, ERBB3, and HPV status). Results: Patients (N =121) were randomized (duligotuzumab:cetuximab; 59:62), median age 62 y; ECOG 0-2. Both arms (duligotuzumab vs. cetuximab, respectively) showed comparable progression-free survival (4.2 vs. 4.0 months; HR: 1.23 [90% CI: 0.89-1.70]), overall survival (7.2 vs. 8.7 months; HR 1.15 [90% CI: 0.81-1.63], and objective response rate (12% vs. 14.5%), with no difference between patients with NRG1-high tumors or ERBB3-low tumors. Responses in both arms were confined to HPV-negative patients. Grade ≥3 adverse events (duligotuzumab vs. cetuximab, respectively) included infections (22% vs. 11.5%) and GI disorders (17% vs. 7%) contributing to higher rates of serious adverse events (41% vs. 29.5%). Metabolic disorders were less frequent with duligotuzumab (10% vs. 16%); any grade rash-related events were less with duligotuzumab (49% vs. 67%). Conclusion: While several lines of preclinical evidence had supported the premise that the blockade of HER3 in addition to that of EGFR may improve outcomes for patients with R/M SCCHN overall or specifically in those patients whose tumors express high levels of NRG1, this study provided definitive clinical evidence refuting this hypothesis. Duligotuzumab did not improve patient outcomes in comparison to cetuximab despite frequent expression of NRG1. These data indicate that inhibition of EGFR alone is sufficient to block EGFR-HER3 signaling, suggesting that HER2 plays a minimal role in this disease. Extensive biomarker analyses further show that HPV-negative SCCHN but not HPV-positive SCCHN are most likely to respond to EGFR blockage by cetuximab or duligotuzumab.

Purpose Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK₁ receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT₃ RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study. Methods This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25–120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0–120 h) CR in cycles 2–4 and by assessing the probability of sustained CR over multiple cycles. Results Of 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1–4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles. Conclusions NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.

Breast cancer requires complex clinical care. Well-being is an intricate concept, encompassing physical, functional, emotional, and social aspects. Background: This study aims to evaluate the relationship between the type of surgery our patients underwent and the timing of the reconstructive surgery with physical, emotional, social, and functional well-being. Furthermore, through our research we tried to identify potential mental health comorbidities in patients with breast cancer, clinical symptoms, and well-being in women with breast cancer, depending on the type of required surgery. Methods: The study included 69 women diagnosed with breast cancer, in stages I to III, divided in two groups: I—patients with oncoplastic breast-conserving surgery and contralateral correction surgery, for symmetry reasons; II—patients who underwent modified radical mastectomy and late breast reconstruction with contralateral symmetrisation. We evaluated socio-demographic aspects, alongside depression, anxiety, stress (DASS 21), and well-being (FACT-B). Data were statistically processed; statistical significance was set at p < 0.05. Results: Clinical elements of depression, anxiety, and stress were noted in both groups, without statistical significance (p > 0.05). Significant differences were found regarding psycho-emotional (p = 0.035) and functional well-being (p = 0.001), with higher scores for group I. The chi-square test indicated statistically significant differences (at p < 0.01) between the groups, regarding the frequency of scores on items B4 and B9 (FACT-B items, related to feminine aesthetics and desirability), with evidently higher scores in group I than in group II. Conclusions: The state of well-being, as well as the items related to femininity and sexuality had higher values in the group of women treated by oncoplastic conservative surgery compared to late reconstruction after modified radical mastectomy.

Background: The surgical treatment of breast cancer involves various psychological consequences, which differ according to individual characteristics. Our study aimed to identify the role that cognitive schemas had in triggering anxiety and depressive symptoms in patients diagnosed with breast cancer that underwent oncological and plastic surgery treatment. Methods: 64 female patients, diagnosed with breast cancer from an Oncology and Plastic Surgery Hospital, were selected to participate in this study between March–June 2018. They were divided into two groups: I. 28 patients who underwent mastectomy surgery; II. 36 patients, who required mastectomy and, subsequently, also chose to undergo breast reconstruction surgery. For the purposes of evaluating a possible change in mental health status, we employed two assessment scales: the Young Cognitive Schema Questionnaire - Short Form 3 (YSQ-S3) and the Romanian version of the Depression Anxiety Stress Scale – 21 (DASS-21R). Results: Participants who underwent mastectomy and subsequent breast reconstruction surgery employed cognitive schemas that did not generate symptoms of depression or anxiety. In contrast, the cognitive schemas found in women who refused reconstructive breast surgery were significantly correlated with the presence of anxiety-depressive symptoms. The cognitive schema domain of ‘disconnection and rejection’ correlated uncertainly with the presence of anxiety-depressive symptoms for the group with breast reconstruction (Spearman’s ρ = 0.091, p = 0.644), while for the other group the correlation was moderate-strong (Spearman’s ρ = 0.647, p < 0.01). Negative emotional schemas were significantly correlated with the presence of anxiety-depressive symptoms (Spearman’s ρ = 0.598, p < 0.01) in the group of participants without reconstructive surgery. Conclusion: A correct identification of dysfunctional cognitive schemas and coping mechanisms at the commencement of the combined treatment in breast cancer patients could serve as an indicator for the evolution of their mental health, therefore assisting professionals in establishing the most suitable psychological, psychotherapeutic and psychiatric intervention plan.

Background: About 10,000 women are diagnosed with breast cancer and about 2000 women are diagnosed with ovarian cancer each year in Romania. There is an insufficient number of genetic studies in the Romanian population to identify patients at high risk of inherited breast and ovarian cancer. Methods: We evaluated 250 women of Romanian ethnicity with BC and 240 women of Romanian ethnicity with ovarian cancer for the presence of damaging germline mutations in breast cancer genes 1 and 2 (BRCA1 and BRCA2, respectively) using Next-Generation Sequencing (NGS) technology. Results: Of the 250 breast cancer patients, 47 carried a disease-predisposing BRCA mutation (30 patients (63.83%) with a BRCA1 mutation and 17 patients (36.17%) with a BRCA2 mutation). Of the 240 ovarian cancer patients, 60 carried a BRCA mutation (43 patients (72%) with a BRCA1 mutation and 17 patients (28%) with a BRCA2 mutation). In the BRCA1 gene, we identified 18 variants (4 in both patient groups (ovarian and breast cancer patients), 1 mutation variant in the BC patient group, and 13 mutation variants in the ovarian cancer patient group). In the BRCA2 gene, we identified 17 variants (1 variant in both ovarian and breast cancer patients, 6 distinct variants in BC patients, and 10 distinct variants in ovarian cancer patients). The prevailing mutation variants identified were c.3607C>T (BRCA1) (18 cases) followed by c.5266dupC (BRCA1) (17 cases) and c.9371A>T (BRCA2) (12 cases). The most prevalent mutation, BRCA1 c.3607C>T, which is less common in the Romanian population, was mainly associated with triple-negative BC and ovarian serous adenocarcinoma. Conclusion: The results of our analysis may help to establish specific variants of BRCA mutations in the Romanian population and identify individuals at high risk of hereditary breast and ovarian cancer syndrome by genetic testing.