tbuckley/cabot-search huggingface dataset:
A phase I/IIa study of the human anti-CD38 antibody MOR202 (MOR03087) in relapsed or refractory multiple myeloma (rrMM).
Authors: Marc S. Raab, Hartmut Goldschmidt, Hermine Agis, Igor Blau, Hermann Einsele, Monika Martha Engelhardt, Barbara Ferstl, Martin Gramatzki, Christoph Röllig, Katja Weisel, Pia Kloepfer, Dominika Weinelt, Stefan Härtle, Christian Peschel
Journal: Journal of Clinical Oncology (2015)

8574 Background: MOR202 is a HuCAL-derived fully human IgG1 anti-CD38 antibody, with high efficacy in preclinical models of MM. Methods: This is an open-label, dose-escalation study (3 + 3 design) to evaluate the safety and preliminary efficacy of MOR202 in adult patients (pts) with rrMM. We present the data of pts previously treated with ≥ 2 prior therapies including an immunomodulatory drug and a proteasome inhibitor. Pts received 2-hour IV MOR202 every 2 weeks (q2w) (8 dose levels [DLs] from 0.01–16 mg/kg) without dexamethasone (DEX), or 4 or 8 mg/kg (DLs 6 and 7), weekly (q1w) +/- DEX. MOR202 16 mg/kg (DL 8) q1w +/- DEX and combination cohorts with lenalidomide (LEN)/pomalidomide (POM) + DEX are planned, as well as confirmation cohorts. Results: As of December 31st 2014, 38 pts had been treated; 29 and 9 pts in the q2w and q1w DLs, respectively. Median age was 70 (44–80) yrs. The median number of prior treatment lines was 4 (2–10) for all pts. 36 pts (94.7%) developed AEs. The most frequently reported AEs ( > 10%) of any grade were anemia (31.6%), fatigue (28.9%), WBC decreased (21.1%), lymphocyte count decreased (LCD) (21.1%), diarrhea (21.1%), nasopharyngitis (18.4%) and leukopenia (13.2%). Grade ≥ 3 hematologic AEs were LCD (15.8%), WBC decreased (7.9%), leukopenia (5.3%), thrombocytopenia (2.6%) and lymphopenia (2.6%). Infusion-related reactions occurred in 13 pts (34%) receiving MOR202 without DEX, mainly during the first infusion. All were grade 1-2 except for 1 pt grade 3. There have been no treatment-related deaths. PK data demonstrate a significant target-mediated drug disposition effect for most pts treated q2w. In 4/6 pts in the q1w 4 mg/kg cohort MOR202 trough levels show the start of target saturation. Only 1 pt (MOR202 0.15 mg/kg q2w) generated a transient anti-drug antibody response to MOR202. Conclusions: The MTD has not been reached. MOR202 is safe and well tolerated. PK data show the potential for full target occupancy in the majority of pts receiving 8 and 16 mg/kg q1w. These latter DLs of MOR202 will be tested as monotherapy or in combination with DEX, LEN + DEX and POM + DEX in the upcoming cohorts. Efficacy analyses are ongoing. Clinical trial information: NCT01421186.
The response of IFNAR2 to high-dose IFNα2b during a neoadjuvant clinical trial
Authors: W. Wang, H. Edington, U. Rao, D. Jukic, S. Land, J. M. Kirkwood
Journal: Journal of Clinical Oncology (2007)

3027 Background: The appropriate subgroup of melanoma patients to select for high-dose IFNa2b (HDI) adjuvant therapy has been undefined since approval of this modality in 1996. A biomarker appropriate for clinical practice and relevant to the biological effects of this agent would be of great importance. IFNAR2 is required for type I IFN-dependent signaling. Therefore, the response of IFNAR2 during HDI was evaluated during a prospective neoadjuvant clinical trial of HDI. Methods: Following diagnostic biopsy and before definitive surgery, HDI was administered as a neoadjuvant therapy for patients with stage IIIB melanoma, in the context of an IRB-approved protocol UPCI 00- 008, separately reported. Immunohistochemical analysis of IFNAR2 was performed on fixed paired biopsies of 8 patients. Paired-sample permutation tests and two-sample permutation tests were used to evaluate the findings of this study. Mean values of the percentage of IFNAR2 positive cells are presented with standard errors (SE). Results: HDI down-regulates IFNAR2 in both responders and non- responders, from 86.875 ± 5.82 (pre-treatment) to 34.375 ± 9.919 (post-treatment), p = 0.0145. However, the decrease in IFNAR2 differs between responders (25.0 ± 12.583) and non-responders (69.0 ± 3.588), p = 0.021. Conclusions: HDI down-regulates IFNAR2 expression, and may provide a biomarker relevant to HDI benefit, given differences between patients with and without response to neoadjuvant therapy. A larger clinical trial is needed to evaluate these pilot data. No significant financial relationships to disclose.
Surgical therapy of lung metastases from colorectal carcinoma: A single institution retrospective study.
Authors: Blazquez Arroyo Maria, Laura Lema, Robles Diaz Luis, Jose A. Lopez-Martin, Carlos Gomez-Martin, Jorge Adeva Alfonso, Cristina Gravalos Castro, Maria Carmen Riesco Martinez, Asuncion Diaz Serrano, Cesar Muñoz, Lucia Parrilla, Otero Irene, Ruiz Gustavo, Ana Belen Enguita, Antonio Gamez, Hernan Cortes-Funes
Journal: Journal of Clinical Oncology (2014)

e14572 Background: Despite recent advances in multidisciplinary therapy of metastatic colorectal cancer (mCRC), 5-year overall survival rate remains under 10%. Several retrospective series published in the last decade have shown encouraging results of surgery in selected patients (pts) with lung metastases (mets). Methods: Medical records of 77 pts that underwent potentially curative surgical removal of lung mets from CRC at our Institution were reviewed. Study period ran from: November 1994 to October 2013. Main outcome endpoints were: disease free interval (DFI) from lung surgery to relapse, and post-metastectomy overall survival (PMOS) between mets removal and death or last censored follow up event. Results: Median age was 62 years. Primary tumor was located at the rectum in 46% of pts. Median time from surgery of the primary tumor to develop of lung mets was 30 months (1-104). 31 pts (40%) had multiple lesions. Unilateral mets ocurred in 57 pts (74%) while 20 pts had bilateral involvement (26%). 27 pts (35%) underwent more than one surgical procedure. 54 pts (70%) received perioperative chemotherapy. Median follow up was 38 months. Disease relapsed in 42 pts. Median DFI was 10 months (1-42). 16 pts (20%) were alive without relapse 2 years after lung surgery. Multivariate analysis identified time between primary colon resection and pulmonary relapse and perioperative chemotherapy as factors significantly associated to DFI. Patients relapsing later than 24 months from resection of primary colorectal tumor had a median DFI of 15.7 months whereas those with earlier pulmonary relapse had a median DFI of 8.5 months (p=0,03). Median DFI was 13.7 months for pts receiving perioperative chemotherapy versus 6.3 months for those who did not (p=0,01). 33 deaths were reported. Median PMOS was 56 months (8-159). Estimated survival rate at 5 years was 40%. Conclusions: Resection of pulmonary metastasis from mCRC can be potentially curative for some patients. Hence, it is critical a regular surveillance and a multidisciplinary approach to select fit candidates for surgical resection. Some questions remain unanswered as the role of perioperative chemotherapy, and of the use of lung CT scan in follow up of the selected high risk pts.
Morphologic pattern of CD30 distribution within neoplastic cells in Hodgkin lymphoma.
Authors: Ewa Paszkiewicz-Kozik, Grzegorz Rymkiewicz, Michal Osowiecki, Joanna Romejko-Jarosinska, Jan Andrzej Walewski
Journal: Journal of Clinical Oncology (2013)

e19535 Background: CD30 protein is expressed on Hodgkin and Reed-Sternberg (HRS) cells in nearly all cases of classical Hodgkin lymphoma (HL). CD30 is present on a cell membrane and on the Golgi complex of the endomembrane cell system. Given the growing clinical application of CD30 targeting we were interested to see if there is variability in distribution of CD30 protein between the cell surface and the cytoplasm. External exposure of CD30 is most likely a critical condition of successful interaction with the ligand and possibly, a predictive factor for response to CD30 antibody. To our knowledge, clinical data on CD30 expression have not yet been published in the context of cell topography. Methods: The CD30 protein was evaluated in formalin-fixed paraffin-embedded (FFPE) tissue sections by immunohistochemistry (IHC) with monoclonal mouse anti-human antibody CD30 (clone Ber-H2) (Dako). IHC was performed using the EnVision Plus Detection Systems LSAB kit (Dako Corp., Carpinteria, CA), and an antigen-retrieval technique was applied. Morphological pattern (localization of CD30) of CD30 expression was evaluated in each case under a microscope examination. Results: FFPE tissue specimens from 83 newly diagnosed and relapsed (n=78 and n=5, respectively) HL patients were examined. The average (range) of patient age was 39 (18-89), male/female ratio was 1/0.88. Histological subtypes of HL were nodular sclerosis in 87%, mixed cellularity in 8%, lymphocyte rich in 3% of cases, and 1 case of lymphocyte-depleted classical HL. Immunophenotype was typical of classical HL, and HRS cells were positive for CD30 in all cases. Immunostaining for CD30 was present on the Golgi body in 98% of cases, and it was demonstrated on the cell membrane in 27% of cases. Conclusions: In our series of 83 patients with classical HL, predominant pattern of CD30 expression was cytoplasmic (Golgi body), and only 27% of cases demonstrated cell surface expression. We hypothesize that cell surface expression of CD30 protein might predict a response to anti-CD30 antibody that is in the order of magnitude of 30% complete remissions in recurrent HL.
Cross-sectional observational study to describe the clinicopathological and biological characteristics and the management of patients with HER2+ metastatic breast cancer who experienced complete or partial remission or disease stabilization during at least 3 years: LongHer study.
Authors: Pilar Zamora, Juan Angel Fresno-Vara, Angelo Gámez-Pozo, Ramon Perez-Carrion, Luis Manso, Carmen Crespo Massieu, Cesar Mendiola, Isabel Alvarez, Mireia Margeli Vila, Juan Lucas Bayo Calero, Xavier Gonzalez, Ana Santaballa, Eva Maria Ciruelos Gil, Ruth Afonso Gomez, Juan Lao Romera, Gustavo Catalan, Jose Valero Alvarez Gallego, Jose Miramon Lopez, Francisco Javier Salvador Bofill, Manuel Ruiz Borrego
Journal: Journal of Clinical Oncology (2012)

e11081 Background: Trastuzumab has shown an improvement in survival outcomes among patients with HER2+ metastatic breast cancer (MBC). Identification of factors and tumor molecular profiles that may predict long-term remission has become a key-issue. Methods: Multicenter, observational, cross-sectional study. Data were collected from women with HER2+ MBC treated with a trastuzumab-based regimen that experienced CR, PR or SD during at least 3 years. FFPE samples(at least 70% tumor cells)for Microarray Analysis were obtained. L2 Boosting for classification with classical Akaike Information criterion based on the binomial log-likelihood for stopping the boosting iterations algorithm was applied to RNA expression data, to identify variables related to clinical information. Predictive models of long term response were built using a Binary Logistic Regression with the Fisher's scoring. Results: 103 patients.Median age: 58(51-68) years. Metastatic disease diagnosed after a median of 24.7(1.8-51.9) months since primary diagnosis. Predominant type: ductal carcinoma(91.9%) and 59% histological grade III. Hormonal status: Progesterone receptor positive 39.2% and estrogen receptor positive 41.2%. Most common metastatic sites: multiple locations(31.4%), lung(23.5%), bone(14.7%) and liver(13.7%). Overexpression of HER2 assessed by IHC in 98.1% of patients, 91.1% were HER2+(3+) and 18.4% had FISH+ HER2 status. Tumor was positive for p53 (&gt;30%) and Ki67(&gt;20%) in 47.3% and 73.6%. Surgery: 87.4% of patients, 77.5% radical mastectomy. Surgery of metastases was performed on 16.8%. Trastuzumab used in combination in 88.3% with a median number of cycles of 35.5(7.0-46). 68.9% of patients achieved a CR, 20.4% PR and 10.7% had SD, during an overall median time of 55 (43-79) months. 4 patients discontinued trastuzumab due to toxicity. Conclusions: Trastuzumab may provide a substantial long-term survival benefit with a manageable safety profile in these patients. Molecular analysis will be presented in the forthcoming Congress.
An adaptive randomized phase II trial to determine pathologic complete response with the addition of carboplatin with and without ABT-888 to standard chemotherapy in the neoadjuvant treatment of triple-negative breast cancer.
Authors: Tiffany P. Avery, Adam C. Berger, Albert J. Kovatich, Hallgeir Rui, Terry Hyslop, Edith P. Mitchell
Journal: Journal of Clinical Oncology (2013)

TPS1135 Background: Inhibition of poly (ADP-ribose) polymerase (Parp) is a potential targeted therapy for triple-negative breast cancer (TNBC). Clinical trials of Parp inhibitors in metastatic TNBC have shown conflicting results. Issues regarding the use of Parp inhibitors in TNBC include choosing a selective Parp inhibitor and selecting an appropriate chemotherapy backbone. The current trial addresses these questions by combining a validated Parp inhbitor, ABT-888, with carboplatin and paclitaxel. Platinum agents have shown synergy with Parp inhibitors in preclinical models and efficacy in clinical trials. The combination of paclitaxel and carboplatin with Parp inhibitors has shown efficacy in phase I trials. Methods: This is a phase II, two-arm neoadjuvant trial of women with TNBC. Eighty patients will be enrolled. Randomization will follow a 1:1 allocation initially, then will follow a Bayesian adaptive allocation in which each prior response will be evaluated and patients assigned preferentially to the better responding arm. The primary endpoint is pathologic complete response (pCR). Secondary endpoints include correlation of pCR with biomarkers, imaging, and circulating tumor cells (CTCs). Treatment: Arm 1: Paclitaxel 80 mg/m 2 + carboplatin AUC=2 (12 weekly cycles) + filgrastim followed by doxorubicin 60 mg/m 2 + cyclophosphamide 600 mg/m 2 (4 cycles every 3 weeks) + pegfilgrastim. Arm 2: ABT-888 (150mg PO bid) + paclitaxel 80 mg/ m 2 + carboplatin AUC=2 (12 weekly cycles) + (filgrastim) followed by doxorubicin 60 mg/m 2 + cyclophosphamide 600 mg/m 2 (4 cycles every 3 weeks) + (pegfilgrastim). Eligibility: Women ≥ 18 years old with clinical stage IIB or stage IIIA, IIIB, or IIIC untreated TNBC (ER &lt;1% , PR &lt;1% , Her-2/neu 0, 1+ on IHC or 2+ and FISH ratio &lt; 1.8) are eligible. Correlative Studies: Correlation of pCR with tissue expression of CK5, EGFR, ERCC1, Ki-67, Parp1, and longitudinal enumeration of CTCs will be done. Exploratory tissue biomarkers with prognostic and predictive value will be correlated with pCR. Enrollment: The trial will begin accrual in February 2013.
Phase II study of intraperitoneal paclitaxel plus S-1/paclitaxel for gastric cancer with positive peritoneal cytology: CY-PHOENIX trial.
Authors: Masaki Aizawa, Hironori Ishigami, Hiroshi Yabusaki, Atsushi Nashimoto, Haruhiko Imamoto, Motohiro Imano, Hiroharu Yamashita, Kentaro Kishi, Yasuhiro Kodera, Yoshikazu Uenosono, Yoshiyuki Fujiwara, Akio Hidemura, Shigeyuki Tamura, Ryoji Fukushima, Hironori Yamaguchi, Joji Kitayama
Journal: Journal of Clinical Oncology (2017)

96 Background: The presence of free cancer cells in the peritoneal cavity has been known as a poor prognostic factor in gastric cancer patients. Intraperitoneal (IP) paclitaxel (PTX) provides powerful local effects in the peritoneal cavity, and we previously reported the efficacy and safety of a regimen combining IP PTX with S-1/PTX in gastric cancer patients with peritoneal metastasis. This multicenter phase II study was conducted to evaluate the efficacy of IP PTX plus S-1/PTX for gastric cancer with positive peritoneal cytology. Methods: Eligibility criteria included pathologically confirmed gastric adenocarcinoma, intraperitoneal free cancer cells confirmed by peritoneal washing cytology, and no evidence of overt distant metastasis including macroscopic peritoneal metastasis. Patients were administered IP PTX 20 mg/m 2 , intravenous PTX 50 mg/m 2 on days 1 and 8, and S-1 80 mg/m 2 /day on days 1-14, q3 weeks. The primary endpoint was the 1-year overall survival (OS) rate. Secondary endpoints were response rate, negative conversion rate on peritoneal cytology and safety. Results: Thirty eight patients were enrolled and fully evaluated for OS and toxicity. The median number of courses was 12.5 (range 2-35). The 1-year OS rate was 84.2% (95 % confidence interval, 68.2-92.6%). Of 3 patients with target lesions, partial response and stable disease were obtained in 2 and 1 patient(s), respectively. The peritoneal cytology findings converted from positive to negative in 36 (94.7 %) patients. The incidences of grade 3/4 hematological and non-hematological toxicities were 45 % and 26 %, respectively. The frequent grade 3/4 toxicities included neutropenia (23%), leukopenia (7%) and anemia (8%). Regarding adverse events related to IP port, 2 patients developed swelling around the port site. Conclusions: IP PTX with S-1/PTX was suggested to be a promising option for gastric cancer with positive peritoneal cytology through the clearance of cancer cells in the peritoneal cavity. Clinical trial information: UMIN000002850.
Racial disparities in attrition among oncology clinical trial participants.
Authors: Leo Chen, Bernhard J. Eigl, Janice Grant, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2015)

6551 Background: Studies indicate that racial minorities are underrepresented in clinical trials. The outcomes of these minority groups following study enrollment are less clear. Our aims were to compare outcomes between White and non-White patients (pts) enrolled in oncology clinical trials and to determine if there are persistent racial disparities among study participants. Methods: All pts who participated in phase III breast, lung, gastrointestinal (GI) and genitourinary (GU) cancer clinical trials from 1999 to 2013 at any of the regional cancer centers in British Columbia were included. We conducted time-to-event analyses with attrition as the main outcome, defined as the time interval from study randomization to when a participant was removed from study due to 1) a primary disease-related endpoint being reached (e.g. recurrence, progression, or death) or 2) a non-cancer related cause (e.g. treatment toxicity). Multivariate Cox regression models were constructed to examine the impact of race on attrition, while adjusting for age, gender, ECOG, tumor site, and cancer stage. Results: We identified 780 pts with known racial status: 564 (72%) White and 216 (28%) non-White. Median age was 58 years, 70% female, 54%/35% ECOG 0/1, 43% stage IV disease, and 55%/20%/15%,10% enrolled in breast, lung, GI and GU trials, respectively. Attrition occurred in 364 (47%) pts of whom 146 (40%) were due to a primary study endpoint and 218 (60%) were attributable to non-cancer related factors, such as toxicity. Compared to White pts, non-White pts experienced higher overall (43% vs 57%, p = 0.0004) and cause-specific attrition (18 vs 22% and 25 vs 35% for cancer and non-cancer causes, respectively). Multivariate adjusted analysis continued to show that non-White pts faced greater likelihood of attrition due to cancer (HR 1.45, p = 0.012) as well as non-cancer related factors (HR 1.43, p = 0.050). Increased age, poor ECOG, and advanced disease were also associated with worse trial outcomes (all p < 0.05). Conclusions: In addition to underrepresentation in clinical trials, racial minorities were more likely to face attrition during study participation, potentially further hindering the generalizability of study findings in the real world population.
Comparative study of the efficacy of breast cancer neoadjuvant chemotherapy (NAC) in patients (pts) with BRCA1/2 mutation vs sporadic cancer cases versus pts with a family history but no BRCA1/2 mutation.
Authors: Francois P. Duhoux, Yann De Rycke, Marie-Christine Falcou, Francois-Clement Bidard, Youlia M. Kirova, Alexia Savignoni, Severine Alran, Jean-Yves Pierga, Bernard Asselain, Dominique Stoppa-Lyonnet, Anne De La Rochefordiere
Journal: Journal of Clinical Oncology (2013)

1533 Background: During NAC, impaired DNA repair mechanisms may account for the higher response rate of BRCA mutation carriers (group #1) when compared to sporadic cases with no history of breast/ovarian cancer (group #2). In this study, we investigated whether pts with possible BRCAX mutation (i.e. with a family history but no BRCA1/2 mutation, group #3) treated by NAC exhibit a different efficacy (response rate, survival) pattern. Methods: All pts screened for a BRCA1/2 mutation between 1999 and 2010 were selected from the prospectively registered cancer genetics database of Institut Curie. Pts younger than 36 years old were excluded. Pts who received NAC were classified in groups #1 (n=23 mutated pts) or #3 (n=64 non-mutated pts). Group #2 (n=87 sporadic cancer pts) was built to match groups #1 and #3 according to age (+/- 5 years), year of treatment (+/- 2 years), hormone receptor status and taxane or trastuzumab use. Results: Median follow-up was 65 months. Fifty % of pts had cytologically proven axillary nodal involvement before NAC. Taxanes were used in 63% of pts and trastuzumab in 9% of pts. Pathological complete response (pCR) rates were 39.1% in group #1, 17.2% in group #2 and 20.3% in group #3 (p=0.07). For locoregional relapse (LR), the difference between groups was statistically significant (p=0.007). The hazard ratio (HR) for LR was higher in group #1 (HR=7.86, p=0.002) than in group #2. No significant difference was seen between group #3 and group #2 (HR=2.37, p=0.15). The difference between groups was also statistically significant for distant metastasis relapse (DMR) (p=0.009). The HR for DMR was higher in group #1 than in group #2 (HR=4.57, p=0.01) and in group #3 than in group #2 (HR=2.81, p=0.01). Conclusions: While pts with BRCA1/2 mutations have a trend towards higher pCR rates with NAC, they have higher rates of LR and DMR than sporadic cases. Pts with a positive family history but no BRCA1/2 mutation have similar pCR and LR rates than sporadic cases, but they have higher rates of DMR. Whether these differences translate into overall survival differences remains to be studied.