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BACKGROUND:In the EMBRACA phase III study (NCT01945775), talazoparib was associated with a significantly prolonged progression-free survival (PFS) compared with physician's choice of chemotherapy (PCT) in germline BRCA1/2-mutated HER2-negative advanced breast cancer (ABC). Herein, the safety profile of talazoparib is explored in detail. MATERIALS AND METHODS:Overall, 412 patients received ≥1 dose of talazoparib (n = 286) or PCT (n = 126). Adverse events (AEs) were evaluated, including timing, duration, and potential overlap of selected AEs. The relationship between talazoparib plasma exposure and grade ≥3 anemia was analyzed. Time-varying Cox proportional hazard models assessed the impact of dose reductions on PFS. Patient-reported outcomes (PROs) in patients with common AEs and health resource utilization (HRU) were assessed in both treatment arms. RESULTS:The most common AEs with talazoparib were hematologic (195 [68.2%] patients) and typically occurred within the first 3-4 months of receiving talazoparib. Grade 3-4 anemia lasted approximately 7 days for both arms. Overlapping grade 3-4 hematologic AEs were infrequent with talazoparib. Higher talazoparib exposure was associated with grade ≥3 anemia. Permanent discontinuation of talazoparib due to hematologic AEs was low (

BACKGROUND:In the EMBRACA phase III study (NCT01945775), talazoparib was associated with a significantly prolonged progression-free survival (PFS) compared with physician's choice of chemotherapy (PCT) in germline BRCA1/2-mutated HER2-negative advanced breast cancer (ABC). Herein, the safety profile of talazoparib is explored in detail. MATERIALS AND METHODS:Overall, 412 patients received ≥1 dose of talazoparib (n = 286) or PCT (n = 126). Adverse events (AEs) were evaluated, including timing, duration, and potential overlap of selected AEs. The relationship between talazoparib plasma exposure and grade ≥3 anemia was analyzed. Time-varying Cox proportional hazard models assessed the impact of dose reductions on PFS. Patient-reported outcomes (PROs) in patients with common AEs and health resource utilization (HRU) were assessed in both treatment arms. RESULTS:The most common AEs with talazoparib were hematologic (195 [68.2%] patients) and typically occurred within the first 3-4 months of receiving talazoparib. Grade 3-4 anemia lasted approximately 7 days for both arms. Overlapping grade 3-4 hematologic AEs were infrequent with talazoparib. Higher talazoparib exposure was associated with grade ≥3 anemia. Permanent discontinuation of talazoparib due to hematologic AEs was low (

Background: The importance of clinical staging in breast cancer has increased owing to the wide use of neoadjuvant systemic therapy (NST). This study aimed to investigate the current practice patterns regarding clinical nodal staging in breast cancer in real-world settings. Materials and Methods: A web-based survey was administered to board-certified oncologists in Korea, including breast surgical, medical, and radiation oncologists, from January to April 2022. The survey included 19 general questions and 4 case-based questions. Results: In total, 122 oncologists (45 radiation, 44 surgical, and 33 medical oncologists) completed the survey. Among them, 108 (88%) responded that clinical staging before NST was primarily performed by breast surgeons. All the respondents referred to imaging studies during nodal staging. Overall, 64 (52.5%) responders determined the stage strictly based on the radiology reports, whereas 58 (47.5%) made their own decision while noting radiology reports. Of those who made their own decisions, 88% referred to the number or size of the suspicious node. Of the 75 respondents involved in prescribing regimens for neoadjuvant chemotherapy, 58 (77.3%) responded that the reimbursement regulations in the selection of NST regimens affected nodal staging in clinical practice. In the case-based questions, high variability was observed among the clinicians in the same cases. Conclusions: Diverse assessments by specialists owing to the lack of a clear, harmonized staging system for the clinical nodal staging of breast cancer can lead to diverse practice patterns. Thus, practical, harmonized, and objective methods for clinical nodal staging and for the outcomes of post-NST response are warranted for appropriate treatment decisions and accurate outcome evaluation. Nodal stage serves a pivotal role in making treatment decisions in breast cancer patients. This study investigated current practice patterns regarding clinical nodal staging in breast cancer in a real-world setting. [ABSTRACT FROM AUTHOR]

Emerging new mutations after treatment can provide clues to acquired resistant mechanisms. Circulating tumor DNA (ctDNA) sequencing has enabled noninvasive repeated tumor mutational profiling. We aimed to investigate newly emerging mutations in ctDNA after disease progression in metastatic colorectal cancer (mCRC). Blood samples were prospectively collected from mCRC patients receiving palliative chemotherapy before treatment and at radiological evaluations. ctDNA from pretreatment and progressive disease (PD) samples were sequenced with a next‐generation sequencing panel targeting 106 genes. A total of 712 samples from 326 patients were analyzed, and 381 pretreatment and PD pairs (163 first‐line, 85 second‐line and 133 later‐line [≥third‐line]) were compared. New mutations in PD samples (mean 2.75 mutations/sample) were observed in 49.6% (189/381) of treatments. ctDNA samples from later‐line had more baseline mutations (P =.002) and were more likely to have new PD mutations (adjusted odds ratio [OR] 2.27, 95% confidence interval [CI]: 1.40‐3.69) compared to first‐line. RAS/BRAF wild‐type tumors were more likely to develop PD mutations (adjusted OR 1.87, 95% CI: 1.22‐2.87), independent of cetuximab treatment. The majority of new PD mutations (68.5%) were minor clones, suggesting an increasing clonal heterogeneity after treatment. Pathways involved by PD mutations differed by the treatment received: MAPK cascade (Gene Ontology [GO]: 0000165) in cetuximab and regulation of kinase activity (GO: 0043549) in regorafenib. The number of mutations revealed by ctDNA sequencing increased during disease progression in mCRC. Clonal heterogeneity increased after chemotherapy progression, and pathways involved were affected by chemotherapy regimens. [ABSTRACT FROM AUTHOR]

Objective: Patients with breast cancer receiving neoadjuvant chemotherapy are at increased risk of poor health‐related quality of life (HRQOL). This study examined clinical caseness on depression and anxiety mediate the relationship between resilience and HRQOL in patients with breast cancer. Methods: A total of 193 patients with breast cancer undergoing neoadjuvant chemotherapy completed questionnaires including the Connor–Davidson Resilience Scale, Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Cancer Therapy‐Breast before the first session (T0), before the start of the last session (T1), and 6 months after the end (T2) of chemotherapy. Mediation analyses using a bootstrapping method was performed. Results: The indirect effect (IE) through T1 depression was significant (IE through depression = 0.043, 95% confidence interval [CI] [0.002–0.090]), while IE through T1 anxiety was not significant (IE through anxiety = 0.037, 95% CI [−0.010–0.097]) in the association between T0 resilience and T2 HRQOL. Conclusions: Clinical caseness on HADS depression subscale during chemotherapy was a mediating factor of the relationship between resilience before chemotherapy and HRQOL after chemotherapy in patients with breast cancer receiving neoadjuvant chemotherapy. Depression during chemotherapy in patients with breast cancer may be a target symptom of screening and intervention to maintain the HRQOL after chemotherapy. Also, patients with low resilience are more likely to develop depression during chemotherapy, and clinicians should carefully monitor whether depression occurs in these patients with low resilience. [ABSTRACT FROM AUTHOR]

Background: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) was effective and well-tolerated in patients with metastatic pancreatic adenocarcinoma (mPAC) that progressed on gemcitabine-based therapy in the global NAPOLI-1 trial. Real-world data may further clarify the outcomes and safety profile of nal-IRI + 5-FU/LV in clinical practice. Methods: This retrospective analysis included patients with mPAC who received nal-IRI + 5-FU/LV following gemcitabine-based therapy under a Managed Access Program in Korea. Results: From January 2017 to April 2018, 86 patients across 10 institutions received nal-IRI + 5-FU/LV (median age, 61 years; 60% male; ECOG performance status, 0–1). A total of 35 (41%) and 51 (59%) patients had received less than two and two or more lines of chemotherapy before inclusion, respectively. At a median follow up of 6.4 months, median overall survival (OS) was 9.4 months (95% confidence interval [CI] 7.4–11.4) and median progression-free survival (PFS) was 3.5 months (95% CI 1.3–5.7). Six-month OS and PFS rates were 65.1% and 37.5%, respectively. Objective response and disease control rates were 10% and 55%, respectively. Most common grade 3–4 toxicities were neutropenia (37.2%), nausea (10.5%), vomiting (9.3%), anorexia (8.1%) and diarrhoea (4.7%). Conclusion: Real-life data for Korean patients indicate that, consistent with NAPOLI-1, nal-IRI + 5-FU/LV is effective and well-tolerated in patients with mPAC that progressed on gemcitabine-based therapy. [ABSTRACT FROM AUTHOR]

Background: Cytopenia occurs frequently during cytotoxic chemotherapy. Little is known about the optimal timing of influenza vaccination for patients receiving chemotherapy. This study compared the immunogenicity of an influenza vaccine administered concurrently with chemotherapy (day 1) and within the cytopenic period (day 11) during 3-week cytotoxic chemotherapy cycles.Methods: Adult patients with solid cancer undergoing scheduled 3-week cytotoxic chemotherapy were randomly assigned to receive the 2014-2015 seasonal influenza vaccine on day 1 or 11 during the chemotherapy cycle. Patients were stratified by their age (<60 and ≥60 years) and previous influenza vaccination status. Antibody responses to influenza vaccine strains H1N1, H3N2, and B were measured before and 21 to 28 days after vaccination with a hemagglutination inhibition antibody assay.Results: Ninety-seven patients were randomized into a day 1 group (n = 43) or a day 11 group (n = 54). Eighty-three patients were included in the final analysis. The mean age was 54 (± 11) years. Cancer types included breast (61%) and lung cancer (30%). Baseline characteristics were not significantly different between the groups. Seroprotection rates after vaccination were also not significantly different for the day 1 and 11 groups (strain H1N1, 67% vs 75% [P = .403]; strain H3N2, 77% vs 80% [P = .772]; strain B, 21% vs 27% [P = .472]). Seroconversion rates and postvaccination geometric mean titers were also similar for the groups. Vaccine-related adverse events were more common in the day 11 group (13% vs. 32%; P = .040).Conclusions: The antibody responses to influenza vaccination on days 1 and 11 during a 3-week cytotoxic chemotherapy cycle were comparable. Influenza vaccination can be performed concurrently with cytotoxic chemotherapy or during the cytopenic period. Cancer 2017;123:841-48. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Ampulla of Vater cancer (AoV Ca) is a rare tumor, and its adjuvant treatment has not been established. The purpose of this study was to find out prognostic factors including host immunity and role of adjuvant treatment in AoV Ca. Methods and Findings: We reviewed 227 AoV Ca patients with curative resection. Clinical characteristics, adjuvant treatment, disease-free survival (DFS) and overall survival (OS) were analyzed. Among all patients, 63.9, 36.1 and 33.9% had T1/T2, T3/T4 stage and lymph node-positive disease (LN+), respectively. OS of all patients was 90.9 months (95% CI: 52.9–129.0). OS was different according to neutrophil-to-lymphocyte ratio (HR 1.651, 95% CI: 1.11–2.47), platelet-to-lymphocyte ratio (HR 1.488, 95% CI: 1.00–2.21) and systemic inflammatory index (HR 1.669, 95% CI: 1.13–2.47). In multivariate analysis, adverse prognostic factors for OS included vascular invasion (HR 2.571, 95% CI: 1.20–5.53) and elevated CA 19–9 (HR 1.794, 95% CI: 1.07–3.05). A total of 104 patients (46.3%) received adjuvant treatment (25 out of 111of T1/T2 & LN (-), 79 out of 116 of T3/T4 or LN (+)). In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the longest OS (5-year OS rate: 47.0 vs. 41.4%). Conclusions: Vascular invasion and elevated CA 19–9 were adverse prognostic factors in resected AoV Ca. In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the best survival outcome. Adjuvant treatment should be further defined in AoV Ca, especially with poor prognostic factors. [ABSTRACT FROM AUTHOR]

Background Paclitaxel plus gemcitabine (PG) combination chemotherapy is a preferred chemotherapeutic regimen for patients with metastatic breast cancer (MBC). Eribulin mesylate is a halichondrin non-taxane inhibitor of microtubule dynamics. A recent pooled analysis with eribulin showed improved overall survival (OS) in various MBC patient subgroups pretreated with anthracycline and taxane. Furthermore, eribulin may have less neurotoxicity than paclitaxel. Patients and methods This study was a prospective randomised phase II, open-label, two-arm, multicentre study comparing eribulin plus gemcitabine (EG) with PG chemotherapy as a first-line treatment for patients with human epidermal growth factor receptor 2-negative MBC. We hypothesised that EG chemotherapy would not be inferior to PG chemotherapy. The primary end-point was progression-free survival (PFS), which was estimated to be 70% at 6 months for each arm. The secondary end-points were as follows: OS, neuropathic scale, toxicity and clinical benefit rate. Results A total of 118 patients (median age: 50, 24–66) were enrolled between March 2015 and March 2016 and were randomly assigned to PG ( n = 59 ) or EG ( n = 59 ) chemotherapy. The mean number of metastatic sites was 3 (range 1–8). The 6-month PFS rates for both arms were 72% for EG and 73% for PG ( P = 0.457 ). There was no significant difference in OS between the two groups (not reached versus 21.2 months, P = 0.2234 ). The median number of chemotherapy cycles for both groups was 10 for EG and 8 for PG (range 2–32). Clinical benefit rates were 44% for EG and 49% for PG. Major toxicities were neutropenia and neurotoxicity. Grade II or above neurotoxicity was more common with PG than with EG (13.6% for EG versus 45.8% for PG, P < 0.0001 ). Conclusion EG chemotherapy had similar clinical benefits to PG chemotherapy in terms of PFS but less neurotoxicity. Trial registration KCSG BR13-11; ClinicalTrials.gov , NCT02263495. [ABSTRACT FROM AUTHOR]