bluuebunny/crossref_metadata_2025_split huggingface dataset:
DPX-Survivac and intermittent low-dose cyclophosphamide (CPA) with or without epacadostat (E) in the treatment of subjects with advanced recurrent epithelial ovarian cancer (DeCidE1 trial): T cell responses and tumor infiltration correlate with tumor regression.
Authors: Tanyi Janos Laszlo , Dorigo Oliver , Oza Amit M. , Strauss James Fredric , Pejovic Tanja , Ghamande Sharad A. , Ghatage Prafull , Villella Jeannine A. , Fiset Stephan , MacDonald Lisa Diana , Hrytsenko Olga , Stanford Marianne , Newton Robert C , Leopold Lance , Rosu Gabriela Nicola 
Published: May 2019

5576 Background: DPX-Survivac is a novel T cell activating therapy designed to elicit an effective immune response against recurrent ovarian cancers that express the survivin protein. The survivin specific T cells induced by DPX-Survivac can infiltrate the tumors and are associated with clinical responses. It is likely that achieving an anti-tumor effect requires a favorable ratio of T cells to tumor cells. Epacadostat (E) is an IDO1 enzyme inhibitor that may enhance effector T cell proliferation, shifting the tumor microenvironment (TME) away from an immunosuppressive state toward one supporting productive immune response. Methods: Recurrent ovarian cancer patients with advanced and metastatic progressive disease were treated with DPX-Survivac, intermittent low dose CPA with or without E. In the Phase 1b, 53 subjects were enrolled to receive DPX-Survivac, low dose CPA and E BID. In the Phase 2, 12 subjects were randomized to receive DPX-Survivac and low dose CPA with or without E. The data on immunological responses, biomarkers, and clinical responses were analyzed in relation to the baseline sum of target lesions per RECIST 1.1. Results: The study showed that DPX-Survivac and intermittent low dose CPA with or without E can generate strong T cell responses. The infiltration of tumors with survivin-specific T cells correlates with the observed tumor regression. The sum of target tumor measurements at baseline by RECIST 1.1 correlated with observed clinical benefits. In the group of 15 patients with the baseline sum of target lesions less than 5 cm, all subjects have shown clinical benefits. Four of these subjects reached partial response and remained without progression over a prolonged period. Conclusions: The treatment studied leads to strong survivin-specific T cell responses. Infiltration of tumors by survivin-specific T cells correlated with clinical benefit in treated subjects. A predictive model based on tumor size to improve response to DPX-Survivac in recurrent ovarian cancer is being prospectively explored. Clinical trial information: NCT02785250.
Clinical outcome of sequential chemotherapy after immune checkpoint inhibitors in advanced ovarian cancer.
Authors: Bonilla Luisa , Oza Amit M. , Lheureux Stephanie , Saibil Sam , Chen Shiyi , Lee Yeh Chen , Gray Diana , Colombo Ilaria , Madariaga Ainhoa , Dhani Neesha C. , Bhat Gita , Bowering Valerie , Garg Swati , Yokom Daniel , Cyriac Sunu Lazar , Butler Marcus O. 
Published: May 2019

5580 Background: Immunomodulation through check point inhibition is an important treatment strategy in many cancers. In ovarian cancer (OC) response rates with immune checkpoint inhibitors (ICI) alone are around 10%. Chemotherapy antitumoural effect is driven by cytotoxicity and immunomodulatory effect. ICI treatment reduces tumour induced immune-tolerance improving immunocompetence, essential for chemotherapy effect. We chose to investigate clinical outcomes of chemotherapy post ICI in women with OC. Methods: The Tumor Immunotherapy Program (TIP) database at the Princess Margaret Cancer Centre identified patients with OC treated with chemotherapy after ICI from 2011 to 2018. Evaluation of clinical outcomes including response rate (RR), progression free survival (PFS) and overall survival (OS) was assessed for pre ICI, ICI and post ICI. Results: 40 women with OC were treated with chemotherapy after ICI. 90% had high grade serous histology, 7.5% carcinosarcoma and 2.5% low grade serous. Median number of pre ICI treatment lines was 3 (1-8) and 2 (1-6) in the post ICI setting. Median time of ICI initiation from diagnosis was 3 years. At ICI all patients had PS 0-1 and treated in clinical trials. 2% of the patients had platinum refractory disease, 88% had platinum resistant disease and 10% platinum sensitive disease. 50% were treated with ICI single agent, 16% were treated with ICI combined with chemotherapy, 14% ICI combo and 17% ICI in combination with other agents. Patients were treated for a median of 3 cycles (1-26). 8% experienced PR, 18% SD, no CR were seen. 67% of the patients discontinued treatment due to PD, 25% due to toxicity. Last treatment in pre ICI RR was 35%. First treatment in post ICI RR was 30%. RR for each treatment used in post ICI was 9% for liposomal doxorubicin, 25% for single agent platinum, 29% for weekly paclitaxel and 67% for chemotherapy with bevacizumab. Median PFS in the last pre ICI treatment was 6.5m and 5m in the first post ICI treatment. Median PFS and OS for all the population was 53m and 54m respectively. Conclusions: ICI are associated with modest activity in OC, planned clinical trials exploring systematic sequential therapy integrating ICI, targeted agents and chemotherapy are needed.
A phase II, open labeled, single-arm study of dose-dense paclitaxel plus carboplatin in advanced or recurrent uterine corpus cancer: KCOGG1303 study.
Authors: Hori Kensuke , Nishio Shin , Ushijima Kimio , Kasamatsu Yuka , Kondo Eiji , Takehara Kazuhiro , Kakubari Reisa , Ito Kimihiko 
Published: May 2019

5584 Background: We studied the effectiveness and safety of dose-dense paclitaxel plus carboplatin in advanced or recurrent uterine corpus cancer. Methods: The patient eligibility criteria were women aged 20–75 years with histologically confirmed uterine corpus ; FIGO stage III who had residual tumors, FIGO stage IV, and recurrence after first-line radical treatment, or second-line chemotherapy or radiotherapy. They received paclitaxel (80 mg/m2, days 1, 8, 15) + carboplatin (area under the curve 5, day 1 every 3 weeks). The primary endpoint was the response rate (RR). The secondary endpoints were feasibility, progression-free survival, overall survival, and adverse effects. The threshold RR was set to 40%. The expected RR of this treatment was set to 60%; the number of necessary cases calculated with a type I error of 5% and power of 80% was 44. Considering the existence of dropped cases, we set the target number of cases in this study to 48. Results: Forty-eight patients were registered, and 45 were eligible to receive the treatment. The median age of the patients was 61 years (43–76). Twenty-two patients had recurrence; the others had primary advanced corpus cancer. On histology, there were 10 cases of serous carcinoma, 3 cases of endometrioid carcinoma G3, 2 cases of carcinosarcoma, and 2 cases of clear cell carcinoma. Twenty-eight patients (62%) could receive 6 or more cycles of chemotherapy. The RR (complete, 13 cases; partial, 20 cases) was 73.3% (60.7–86.0 95% confidence interval). Conclusions: Dose-dense paclitaxel plus carboplatin was safe and effective for advanced or recurrent uterine corpus cancer. Clinical trial information: R000019874 UMIN000017138.
Identifying a potential biomarker for anti-PD-1 immunotherapy in patients with advanced stage, surgically-resectable endometrial cancer.
Authors: Fuh Katherine Cynthia , Lomonosova Elena , Guo Lei , Fantl Wendy , Pachynski Russell Kent , Malkova Olga , Oh Stephen T. , Hagemann Andrea R. , McCourt Carolyn K. , Powell Matthew A. , Thaker Premal H. 
Published: May 2019

5590 Background: The FDA approval of pembrolizumab for patients with MSI-H or dMMR tumors has led to the treatment of a select cohort of endometrial cancer (EC) patients. We sought to ascertain tumor immune modulatory effects in the front-line setting for advanced stage III/IV EC patients regardless of MSI-H or dMMR. The primary objective was to determine the safety of preoperative and maintenance pembrolizumab. The secondary objective was to examine pembrolizumab-induced changes in peripheral immune effector phenotype in order to identify potential biomarkers of clinical response. Methods: In an open label, single-arm Phase I trial, 8 EC patients were treated with 2 doses of preoperative pembrolizumab IV prior to surgery followed by chemotherapy and 4 doses of pembrolizumab IV. As an initial study, pre- and post-treatment (on the day of surgery) peripheral blood was collected from 3 patients as well as a healthy control and processed for high-dimensional single-cell mass cytometry (CyTOF) using an optimized antibody panel. Results: Six of 8 patients completed the treatment. One patient had rapid cancer progression and another had an exacerbation of comorbidities. Peripheral blood from 3 patients with pathological response were then immunoprofiled using CyTOF. Data analysis revealed that the frequencies of CD8+ T cells, B cells and CD56hiCD16- NK cells were lower, whereas the frequency of CD14+CD16-HLA-DRhi classical monocytes was higher in the cancer patients compared to controls. Cancer patients had lower frequencies of circulating CD4+ and CD8+ naïve T cells but higher frequencies of effector CD8+ and CD4+ T cells. Notably, the median expression of Granzyme B in CD8+ and CD4+ T cells was higher and median expression of signal regulatory protein (SIRP), CD172a-b on monocytes was lower for cancer patients compared to control. The frequencies of NK and myeloid cells expressing CD137(4-1BB), PD-1+NK cells, and PD-L1+DCs were greater in post-compared to pre-pembrolizumab. Conclusions: This is the first trial to evaluate the use of neoadjuvant pembrolizumab in advanced stage EC patients. Here, we present peripheral immune correlative data and show an increase in markers of activation in patients with pathologic responses to pembrolizumab. Additional data from this ongoing study will help us to identify candidate predictive biomarkers. Clinical trial information: NCT02630823.
Use of nivolumab as salvage therapy in heavily pretreated patients with gynecologic malignancies.
Authors: Williams Heather , Wang Jennifer , Tran Lynn , Mobley Sara , Rungruang Bunja Jane , Ghamande Sharad A. 
Published: May 2019

5593 Background: There are limited effective treatments for gynecologic cancer patients who have been previously treated with multiple lines of chemotherapy. Immune checkpoint inhibitor (ICI) therapy has demonstrated significant activity in certain cancers but has been inconclusive in most gynecologic malignancies. The objective of this study was to determine the impact of salvage ICI therapy in heavily pretreated gynecologic oncology patients. Methods: An IRB approved retrospective study was performed of women with gynecologic cancer treated with nivolumab on a compassionate use program between October 2015 and January 2018. Patient demographics, disease characteristics, pathology and treatment history were collected. Survival probabilities were calculated. Results: Twenty-eight women were identified. Median age at start of treatment was 63 years with a median of 4 prior lines of chemotherapy. Median ECOG status was 2. Disease site was evenly distributed among uterus, ovary and cervix. 67.9% of patients completed 3 or more cycles of treatment. Median PFS of all patients was only 2.6 months however when comparing patients who received 2-3 cycles (n = 13) with those who received 4 or more (n = 9), median PFS was statistically significant 2.4 months vs 6.4 months (p = 0.0005). When looking at treatment response, 7 patients had partial response/stable disease after 3 cycles (25%). Median PFS of the 7 “responders” was 6.6 months vs 2.5 months of the non-responders (p < 0.001). Only 1 of 9 patients with uterine cancer had a disease response and that patient’s tumor was MSI high. Five patients had low grade serous ovarian cancer. Four of them had a treatment response with a median PFS of 6.1 months (range 3.8 – 25 months). Adverse events were experienced by 68% of patients; most commonly being fatigue (46.4%), arthralgia (25%), and anemia (21.4%). Only 1 patient experienced a grade 3-4 event (a diffuse maculopapular rash). Conclusions: In patients with heavily pretreated gynecologic malignancies with suboptimal performance status, immune checkpoint inhibitor therapy may prolong survival without significant toxicity. Also, there may be a role for ICI in patients with historically chemo resistant low grade serous ovarian cancers.
Screening for cancer-related distress among women with newly diagnosed breast cancer (BC).
Authors: Rynar Lauren Z. , Wendell Kristen B. , Mumby Patricia B. , Albain Kathy S. , Robinson Patricia A. , Mai Hanh P. , Grace-Louthen Cathy , Lo Shelly S. 
Published: May 2019

567 Background: The Loyola University Chicago Cardinal Bernardin Cancer Center multidisciplinary Breast Oncology Center evaluates new patients (pts) for cancer-related distress using a needs-based screening tool, in accordance with Commission on Cancer (CoC) Standard 3.2. Identifying distress among newly diagnosed pre-surgical and pre-neoadjuvant pts allows for comprehensive treatment planning and establishment of a baseline for repeated assessments. Methods: Pts with newly diagnosed BC between May 2017 and June 2018 completed the “Patient Screening Questions for Supportive Care” (Coleman Supportive Oncology Collaborative, 2017), a consolidated screening tool based on validated instruments (NCCN Distress, PHQ-4, PROMIS), prior to initial provider visit. Cancer staging, demographics, and supportive oncology referrals were obtained from medical records. Descriptive statistics and chi-square were used. Results: 100 pts aged 30-94 (mean(SD) = 61.56(12.03)) completed the screening tool; 14.9% had Stage 0, 43.6% Stage I, 34.0% Stage II, 3.2% Stage III, and 4.3% Stage IV disease. 39% of pts screened positive for anxiety on the PHQ-4, and over 20% for depression. Anxiety was associated with cancer stage ( X2(df) = 12.20(4), p = .016). The most common practical concerns included living alone (19%), issues with work/school (16%), and paying for medical care (12%). Common physical concerns included difficulty with sleep (40%) and concentration/memory (17%), and tingling hands or feet (14%). Poor sleep was associated with depression ( X2(df) = 6.50(1), p = .011) and anxiety ( X2(df) = 7.17(1), p < .01). 57.7% reported at least "a little bit" of fatigue and 17.7% reported moderate to very severe pain. Nearly all pts wanted to better understand their diagnosis (87.8%), prognosis (87.8%), or treatment (91.8%). Conclusions: Pts with newly diagnosed, early stage BC experience high levels of physical and emotional distress at the earliest point in the treatment trajectory. This study captures BC patients at a unique time point and provides support for conducting routine screening for supportive oncology needs at initiation of care. Further studies should reassess needs sequentially to determine changes across the care continuum.
Biomarker analysis of PALLET: A neoadjuvant trial of letrozole (L) ± palbociclib (P).
Authors: Martins Vera , Kilburn Lucy , Dodson Andrew , Modi Arjun , Pogue-Geile Katherine L. , Rimawi Mothaffar F. , Huggins-Puhalla Shannon Leigh , Bartlett Cynthia Huang , Perry Sophie , Batten Leona , Osborne C. Kent , Jacobs Samuel A. , Johnston Stephen R. D. , Bliss Judith , Dowsett Mitchell ,   On behalf of the PALLET investigators
Published: May 2019

570 Background: PALLET randomized 307 postmenopausal women with ER+ primary breast cancer to one of 4 treatment groups (3:2:2:2 ratio): A: L for 14wks; B: L for 2wks then L+P to 14wks; C: P for 2wks then L+P to 14wks; D: L+P for 14wks. This allowed a randomized 1:2 comparison of L (Group A) vs L+P (Groups B+C+D) at 14wks. P was given 125mg/d PO (21 days on, 7 days off). Adding P to L markedly enhanced Ki67 suppression and Complete Cell Cycle Arrest (CCCA, Ki67 < 2.7%) by 14wks but did not substantially increase clinical response. We now report exploratory analysis of the association of baseline expression of 6 pre-specified biomarkers involved in estrogen and CDK4/6 signaling with CCCA at 14wks and changes in their expression during therapy. Methods: Estrogen receptor (ER), progesterone receptor (PgR), RB and CCNE1 were measured by IHC and CCND1 by IHC and FISH (CCND1/CEP11 ratio≥2.0 amplified). Baseline biomarker values were available with 14wk Ki67 values in up to 64 patients for L alone and up to 124 patients for L+P. Of these 59% and 90%, respectively, achieved CCCA. Results: With L alone CCCA was significantly less frequent (indicating relative resistance) with low baseline PgR (odds ratio [OR] 0.22, 95%CI 0.05-0.96, p = 0.04) or high CCNE1 levels (OR 10.39, 95%CI 1.19-90.48, p = 0.03). With L+P CCCA was also significantly less frequent with high CCNE1 (OR 50.34 95%CI 5.12-495.34, p = 0.001) or with low baseline ER (OR 0.21 95%CI 0.08-0.60, p = 0.004). CCCA was not significantly different with either treatment according to CCND1 amplification status or expression overall. However, CCCA showed a tendency to being less frequent in non-amplified cases with low baseline cyclin-D1 expression when treated with L+P (p = 0.10). There were no significant changes in ER levels or CCND1 amplification over 14wks. By 14 wks PgR, RB, CCND1 and CCNE1 levels were significantly suppressed by L or L+P (geomeans PgR: -96.4% vs -94.9%; CCND1: -79.9% vs -70.7%; CCNE1: -68.2% vs -74.7%; RB: -23.5% vs 26.1%, respectively) and there was no significant difference between the treatments. Conclusions: These data support low ER, possibly indicating limited luminal status, and high CCNE1 as markers of poor Ki67 response to L+P in primary disease and are consistent with findings in studies in advanced disease. Clinical trial information: NCT02296801.
Role of anthracyclines in neoadjuvant anti-HER2 regimens for HER2+ breast cancer (BC): A network meta-analysis (NMA).
Authors: Pelizzari Giacomo , Gerratana Lorenzo , Basile Debora , Bartoletti Michele , Lisanti Camilla , Garattini Silvio Ken , Bortot Lucia , Corvaja Carla , Buriolla Silvia , Curtolo Gianluca , Garutti Mattia , Di Nardo Paola , Torrisi Elena , Da Ros Lucia , Freschi Andrea , Saracchini Silvana , Bolzonello Silvia , Miolo Gianmaria , Spazzapan Simon , Puglisi Fabio 
Published: May 2019

577 Background: It is matter of current debate which would be the best chemotherapy backbone of neoadjuvant HER2-targeted therapy for HER2+ BC. The TRAIN 2 trial showed no significant difference in terms of pathological complete response (pCR) when anthracyclines–based (CTA) or anthracyclines–free regimens (CT) were combined with dual HER2 blockade. However, it remains unclear how anthracyclines may influence the relative benefit across different anti-HER2 treatments. Methods: A systematic review was conducted which included all phase II/III randomized clinical trials (RCTs) comparing different neoadjuvant regimens for HER2+ BC. pCR (yT0/isN0) was the outcome of interest. Indirect comparisons of all combination of anti-HER2 agents with CTA or CT were estimated with a random-effects frequentist NMA. Estimated pCR rates were inferred adopting a Bayesian NMA. Results: 17 RCTs (3933 patients) were included. Overall, 8 arms were identified, comprising all possible combinations of CTA and CT with trastuzumab (H), lapatinib (L) and dual HER2 blockade (D) but also CTA and D only. Odds ratios (OR) for pCR and 95% confidence interval (CI) of selected NMA comparisons are shown in the table. Estimated rates of pCR for each treatment and 95% credible interval (CrI) are reported in the table. Conclusions: Through indirect comparisons, no significant pCR gain was found for CTA vs CT when combined to D, H and L. In particular, considering double vs single-agent anti-HER2 regimens, D-CT remains superior to H-CTA, supporting a possible omission of anthracyclines when dual anti-HER2 block is used. On the contrary, our pooled estimate suggests a more relevant role for anthracyclines when comparing H-CT/A vs CTA. Moreover, we estimated a 4% pCR gain for D-CTA vs D-CT, and an 8% higher pCR rate for H-CTA vs H-CT. [Table: see text]
Correlation between mutation landscape and clinical outcomes of neoadjuvant therapy in HER2-positive breast cancer patients.
Authors: Liao Ning , Wang Yulei , Li Kai , Chen Bo , Zhang Guo-Chun , Li XueRui , Guo Liping , Cao Li , Ren Chong-Yang , Wen Ling-Zhu , Jia Minghan , Li Cheukfai , Mok Hsiaopei , Chen Xiaoqing , Wei Guangnan , Lin Jiali , Hou Ting , Han-Zhang Han , Zhang Zhou , Liu Jing 
Published: May 2019

579 Background: The standard management of early stage human epidermal growth factor receptor 2 (HER2) positive (+) breast cancer (BC) involves neoadjuvant therapy with combination of chemotherapy and HER2-targeted therapy followed by surgery. However, diverse pathologic responses were observed. We interrogated whether baseline genomic heterogeneity contributes to the varied therapeutic responses. Methods: Capture-based targeted sequencing using a panel consisting of 520 cancer-related genes, spanning 1.6MB of human genome, was performed on tissue biopsy samples, obtained prior to neoadjuvant therapy, of 33 HER2+ women with stage I-III BC. The median age of the cohort was 53. The correlation between genomic alterations and pathologic response were analyzed by multivariate analysis. Results: A majority of them was diagnosed with stage II (67%, 22/33), while 30% (10/33) had stage III and 3% (1/33) had stage I disease. 58% (19/33) were HR+ and 42% (14/33) were HR-. Mutation profiling of baseline samples revealed 349 mutations spanning 145 genes, with TP53, CDK12 and PIK3CA being the top 3 most frequently mutated genes. Neoadjuvant regimen was comprised of trastuzumab and HER2 inhibitor (i.e. pertuzumab or lapatinib). 15 patients used single HER2 inhibitor;18 used dual HER2 inhibitors. Endocrine therapy was also administered to HR+ patients (19/33) in combination with trastuzumab and HER2 inhibitor. Complete pathologic response (pCR) was observed in 45.5% (15/33) of patients. Interestingly, ROS1 copy number amplifications (CANs) were only identified in patients achieved pCR (p = 0.033). In contrast, missense mutations in PIK3CA and CNAs in CCND1, FGF19, FGF3, FGF4, SPOP, HNF1B and BRIP1 showed a trend of being less likely to mutate in pCR patients (p values between 0.05-0.1). Previous reports have suggested that pCR rates in HER2+ patients are associated with HR status. However, our data revealed comparable pathologic response of patients based on either HR status or neoadjuvant regimen. Conclusions: Our data revealed a distinct mutational profile between patients achieved pCR vs patients did not. Further studies with a larger cohort are required to confirm these findings.