tbuckley/cabot-search huggingface dataset:
SOLTI NeoPARP: A phase II, randomized study of two schedules of iniparib plus paclitaxel and paclitaxel alone as neoadjuvant therapy in patients with triple-negative breast cancer (TNBC).
Authors: Antonio Llombart, Ana Lluch, Cristian Villanueva, Suzette Delaloge, Serafin Morales, Judith Balmaña, Kepa Amillano, Herve R. Bonnefoi, Ana Maria Casas, Luis Manso, Henri Hubert Roche, Santiago Gonzalez-Santiago, Joaquin Gavila, Pedro Sánchez-Rovira, Serena Di Cosimo, Eric Charpentier, Ignacio Garcia-Ribas, Frederique Madeleine Penault-Llorca, Claudia Aura, José Baselga
Journal: Journal of Clinical Oncology (2012)

1011 Background: Iniparib is an anticancer agent with a mechanism of action still under investigation. A phase 2 randomized neoadjuvant study in patients (pts) with TNBC was designed to explore the activity and tolerability of two schedules of iniparib with weekly paclitaxel (PTX). Here we report the efficacy and safety results from a planned interim analysis (IA). Methods: The trial accrued a total of 141 pts in October 2011, of whom, 74 are included in this IA. All were chemo-naive, histologicallyconfirmed Stage II-IIIA TNBC (IIA 47%; IIB 35%; IIIA 16%) with a median age of 50 yr. Triple negative status was centrally confirmed [ER/PR &lt;10%, HER2 IHC (0+, 1+) or FISH negative]. Pts were randomized (1:1:1) to receive weekly PTX (80 mg/m 2 , IV, d 1; N=25) alone or in combination with iniparib, either on a once weekly (QW) (11.2 mg/kg, IV, d 1; N=25) or twice weekly (BIW) (5.6 mg/kg, IV, d 1, 4; N=24) schedule. The total planned treatment duration was 12 wks. The IA endpoint is pathological complete response in the breast (pCR) as assessed by independent pathologists. Results: Two/2/3 pts in the PTX/QW/BIW arms, respectively, discontinued due to progressive disease per RECIST. Another 3/2/2 pts, respectively, discontinued due to investigator decision or an adverse event (AE). Thirteen pts presented with Grade 3/4 Treatment Emergent AE: 3 pts in PTX arm (1 neutropenia, 1 presyncope, 1 ALT elevation), 3 in QW arm (1 lymphopenia, 1 hyperkalemia, 1 pulmonary embolism), and 8 in the BIW arm (1 febrile neutropenia, 3 neutropenia, 1 aphonia, 1 syncope, 1 radius fracture and 1 vertigo). Laboratory Grade 3/4 neutropenia occurred in 4% of pts in PTX, 0% in QW and 21% of BIW arms, with 1/2/3 pts, respectively, requiring G-CSF usage. There were 4/7/6 pts in the PTX/QW/BIW arms with PTX dose modifications. Four pts (16%) in PTX arm, 4 pts (16%) in the QW arm and 6 pts (25%) in the BIW arm had confirmed pCR in the breast. Conclusions: In this IA population, the addition of iniparib regardless of the schedule to weekly PTX did not seem to add clinically significant toxicity. pCR rate in the breast is similar across treatment arms at this IA. NCT01204125.
Final data from CALM: A phase II study of Coxsackievirus A21 (CVA21) oncolytic virus immunotherapy in patients with advanced melanoma.
Authors: Robert Hans Ingemar Andtbacka, Brendan D. Curti, Howard Kaufman, Gregory A. Daniels, John J. Nemunaitis, Lynn E. Spitler, Sigrun Hallmeyer, Jose Lutzky, Stephen Michael Schultz, Eric D. Whitman, Karl Zhou, Roberta Karpathy, Jeffrey Ira Weisberg, Mark Grose, Darren Shafren
Journal: Journal of Clinical Oncology (2015)

9030 Background: CVA21 (CAVATAK) is a novel bio-selected oncolytic and immunotherapeutic strain of Coxsackievirus A21. Intratumoral (i.t) CVA21 injection initiates preferential tumor cell infection, cell lysis and enhancement of a systemic anti-tumor immune response. Presented are the final data of the open-label, multicenter Phase II CALM (CAVATAK in Late stage Melanoma) study. Methods: The CALM study investigated the efficacy and safety of i.t CVA21 in 57 patients with treated or untreated unresectable Stage IIIC-IVM1c melanoma. Pts received up to 3 x 108 TCID50CVA21 i.t on study days 1,3,5, 8 and 22, and then every three weeks for a further 6 injections. Pts displaying immune-related progression-free survival (irPFS) or better at 6 mos were eligible for 9 additional injections. Key eligibility criteria were ≥ 18 yrs old, ECOG PS 0-1, and at least 1 injectable cutaneous, subcutaneous, or nodal melanoma metastasis ≥ 1.0 cm. The primary endpoint was to achieve > 9 of 54 evaluable pts with irPFS at 6 mos. Secondary endpoints included irRECIST overall response rate, durable response rate (continuous response ≥ 6mos), median time to response and 1-year survival. Results: The primary endpoint of the study was achieved with 21 of 57 (38.6%) evaluable pts displaying irPFS at 6 mos with a median irPFS of 4.2 mos. The overall response rate (irRECIST) was 28.1% (16 of 57 evaluable pts) with a ≥ 6 mos durable response rate of 19.3 % (11 of 57 pts). The median time to response was 2.8 mos, and the 1-year survival rate 75.4% (43 of 57 pts). After a median follow-up of ~16.5 mos, median duration of response in responders and median OS for all pts was not reached. The most common AE's were Grade 1 fatigue, chills, local injection site reactions and fever. No Grade 3 or 4 product-related AE's were observed. Conclusions: Intralesional CVA21 is a promising novel oncolytic immunotherapeutic agent for the treatment of unresectable Stage IIIC-IVM1c melanoma and the CALM study met its primary endpoint of irPFS at 6 mos. CVA21 was well tolerated and exhibited both local and distant durable tumor responses. Further clinical studies using CVA21 in combination with other immunotherapies are underway. Clinical trial information: NCT01227551.
EGFr expression and clinical outcome in head and neck cancer patients treated with radiotherapy with or without cetuximab
Authors: J. A. Bonner, P. M. Harari, J. Giralt, R. B. Cohen, J. M. Baselga, S. A. Spencer, N. Azarnia, E. K. Rowinsky, N. Amellal, K. K. Ang
Journal: Journal of Clinical Oncology (2006)

5510 Background: Increased expression of epidermal growth factor receptor (EGFr) has been correlated with poor outcome for patients with squamous cell carcinoma of the head and neck (SCCHN). This analysis was performed to examine the prognostic significance of EGFr expression in patients with locoregionally advanced SCCHN treated with radiotherapy (R) with or without cetuximab (C, an IgG1 anti-EGFr monoclonal antibody). Methods: This correlative study was performed on tumor biopsy samples from patients with locoregionally advanced SCCHN who were randomized to R with or without C as previously described (ASTRO Abstract #120, 2005). Immunohistochemistry was utilized to assess the percentage of tumor cells that stained for EGFr (JCO 23:5568, 2005). Kaplan-Meier estimates of locoregional control and survival were derived, and Cox regression was used to adjust for differences in prognostic factors. Results: Tumor specimens were evaluated from 339 of the 424 randomized patients. The median percentage of EGFR-detectable tumor cells (EDTC) was 50%. 183 patients had ≤50% EDTC, whereas 156 patients had &gt;50% EDTC. The addition of C to R resulted in improved locoregional control (LRC, p = 0.005) and survival (p = 0.03) in the overall study. The LRC and survival results are summarized for patients with ≤50% EDTC and patients with &gt;50% EDTC. Medians are measured in months. These findings were not altered after adjusting for imbalances in known prognostic factors of Karnofsky score (90–100 vs. 60–80) and primary site (Oropharynx or Larynx vs. Hypopharynx). Conclusions: A high positive EGFr expression in SCCHN, as determined by current methodology, is not necessary for response to radiotherapy and cetuximab. These results warrant further evaluation. [Table: see text] [Table: see text]
Multidimensional investigation of HER2 in advanced urothelial carcinoma (UC).
Authors: Rachel S. Park, Lillian Werner, Heidi Greulich, Silvia de Muga, Marta Salido, Edward C. Stack, Rosina Lis, Fabio A. B. Schutz, Josep Lloreta Trull, Enrique Gallardo, Federico Rojo, David M. Berman, Joaquim Bellmunt Molins, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2012)

4580 Background: Incidence of Her2 positivity and association with overall survival (OS) are controversial in advanced UC. Activating Her2 mutations have been identified in other cancers, but they have not been previously reported in UC. We determined Her2 status by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and copy number gain (CNG) via array CGH of primary UC tumors from patients (pts) with metastatic disease. Targeted Her2 sequencing was performed at known mutation hotspots, and mutation effect was investigated in vitro. Methods: Tissue microarrays of formalin fixed paraffin-embedded tumor from 98 UC pts treated with platinum-based combination chemotherapy for metastatic disease were evaluated for Her2 protein and for Her2 gene amplification by using standard clinical protocols. Positive staining was defined as an IHC score of 3+ or a FISH ratio of ≥2 using scoring criteria established for evaluation of breast cancer. Her2 CNG was evaluated by aCGH with cutoff log base 2 ratio &gt; 0.9. Mutation status was validated by hME sequencing. OS was measured from start of treatment for metastatic disease. Association of OS and Her2 status was assessed by a Cox regression model. NIH-3T3 cells with Her2 V777L were assessed for growth, invasion, and Her2 kinase activation. Results: 22% of pts had 3+ Her2 staining by IHC. 21% of pts had FISH amplification. These were concordant in 78% of pts. CNG was identified in 16% and was concordant with FISH and IHC 85% and 88% of the time, respectively. Her2 status by any modality showed no significant association with OS in either univariate [HR=0.94, 95% CI: (0.52, 1.70), p=0.83] or multivariate [HR=1.12, 95% CI: (0.61, 2.06), p=0.72] analysis. Her2 mutations (V777L and L755S) were identified in 2 pts (2%). In vitro analysis of V777L results in transformation of NIH-3T3 cells, leading to increased growth, invasion on soft agar, and Her2 kinase constitutive activation. Conclusions: Her2 overexpression or amplification in the primary tumor does not predict OS in pts with metastatic UC. Other research has suggested that V777L sensitizes cells to lapatinib, while L755S leads to lapatinib resistance. These rare oncogenic Her2 mutations occur and may be therapeutic targets in selected pts.
E2112: Randomized phase III trial of endocrine therapy plus entinostat/placebo in patients with hormone receptor-positive advanced breast cancer.
Authors: Roisin M. Connolly, Fengmin Zhao, Kathy Miller, Amye Tevaarwerk, Lynne I. Wagner, Min-Jung Lee, Judy Murray, Robert James Gray, Richard Piekarz, Jo Anne Zujewski, Joseph A. Sparano
Journal: Journal of Clinical Oncology (2015)

TPS636 Background: A potential mechanism of resistance to endocrine therapy in breast cancer involves changes in gene expression secondary to epigenetic modifications, which might be modulated with the use of histone deacetylase (HDAC) inhibitors such as entinostat. ENCORE 301, a phase II study evaluating the addition of entinostat to the steroidal aromatase inhibitor (AI) exemestane in patients with hormone receptor (HR)-positive advanced breast cancer who had experienced disease progression after a non-steroidal AI (NSAI), showed a significant improvement in progression-free survival (PFS), and overall survival (OS). Entinostat has been designated a Breakthrough Therapy by the FDA. Methods: E2112 is a multicenter randomized double-blind placebo-controlled phase III study (NCT02115282) enrolling patients with advanced HR-positive, HER2-negative breast cancer with prior disease progression on a NSAI (n = 600). Patients receive exemestane 25mg po daily and entinostat/placebo 5mg po every week. Eligibility:...
Evaluation of resources used during care of children with high-risk neuroblastoma (HR NBL) via merging of cooperative group trial data and administrative data.
Authors: Rochelle Bagatell, Brian Fisher, Alix Eden Seif, Yuan-Shung Huang, Yimei Li, Ami Vijay Desai, Wendy B. London, Collin Van Ryn, Julie R. Park, Troy Richardson, Matt Hall, Richard Aplenc
Journal: Journal of Clinical Oncology (2014)

10069 Background: Cooperative group trials have improved outcomes for children with HR NBL. Trial data provide reliable information regarding patient characteristics, treatment, and response but do not include information regarding resource utilization. Merging of trial and administrative data would facilitate comparative effectiveness studies. Methods: Data from the Children's Oncology Group (COG) and the Pediatric Health Information Systems (PHIS) were merged for patients (pts) enrolled on Phase 3 COG trials for HR NBL (A3973 and ANBL0032) at 43 PHIS centers. A3973 included induction chemotherapy, surgery, stem cell transplant, and radiation. Responders were eligible for ANBL0032, a randomized trial of chimeric antibody, cytokine and isotretinoin vs isotretinoin alone. Inpatient resource utilization summary statistics were tabulated based on PHIS data. Results: Of 323 enrollments on A3973 and/or ANBL0032 at PHIS centers, matching was successful and resource utilization data were available for 223 pts. The median age of newly diagnosed pts was 3.19 years (range 0.3-16.09) and 163 (88%) children had Stage 4 disease. Sixty-six (36%) had MYCN amplified tumors, 145 (87%) had unfavorable histology. Pts treated on A3973 for whom complete data were available (n=192) were hospitalized for a median of 100 days (d). Of these, 75 (39%) required intensive care resources; these services were delivered for a median of 4d per pt. Median cumulative duration of antibiotic use was 72d per pt. Ototoxic antibiotics were administered to 44% of pts; these were delivered for a median of 6d in total (range 1-93). Conclusions: Pts enrolled on cooperative group HR NBL studies can be successfully identified and resource utilization data can be collected across trials using an administrative dataset. Characteristics of pts in this cohort are consistent with those of pts on recent HR NBL studies. Information regarding length of stay and supportive care required for treatment of children with HR NBL will be used in comparative effectiveness studies and will aid in patient/family education. A larger cohort, created by adding pts from future trials, will permit additional analyses.
Positron emission tomography and stage migration for head and neck cancer.
Authors: Noam Avraham VanderWalde, Ramzi George Salloum, Tsai-Ling Liu, Mark Christopher Hornbrook, Maureen Cecelia O'Keeffe-Rosetti, Debra Pearson Ritzwoller, Paul Arthur Fishman, Jennifer Elston Lafata, Amir H Khandani, Bhishamjit S. Chera
Journal: Journal of Clinical Oncology (2013)

6018 Background: Positron emission tomography (PET) is often used for the staging of head and neck cancer (HNC). The purpose of this study is to explore the association between the increased utilization of PET and stage/survival in the managed care environment. Methods: Adult patients diagnosed with HNC (n=958) between 2000-2008, at 4 integrated health systems (Group Health Cooperative, Seattle; Health Alliance Plan/Henry Ford Health System, Detroit; Kaiser Permanente Colorado and Northwest, Portland) were identified via tumor registries linked to claims data. We compared AJCC stage distribution, patient/treatment characteristics, and survival between pre-PET era (2000-2004) vs. PET era (2005-2008), and those with PET vs. those without, during the PET era. AJCC stage was grouped into stage I/II (localized), stage III/IVa/IVb (locally advanced), and stage IVc (metastatic). Ordered logistic regression estimated the effects of PET utilization on upstaging. Kaplan-Meier estimates described overall survival (OS) differences between PET users and nonusers in the PET era. Cox proportional hazards regression evaluated the effect of PET use on survival. Results: There was a non-significant increase in stage III/IVa/IVb (40% to 44%) with a decrease in stage I/II (58% to 52%) between pre-PET era and PET era (p=0.11). During the PET era, patients with PET were more likely stage III/IVa/IVb and less likely stage I/II compared to patients without PET (III/IVa/IVb: 62% vs. 29%, I/II: 35% vs. 68%). On multivariate analysis those who were staged with PET were twice as likely to have locally advanced disease (OR 2.091; p=0.006). There was no difference in stage IVc. Patients with PET scans were more likely to receive chemotherapy with radiation and less likely to receive no treatment. 3-year actuarial OS for patients (all stages) with and without PET was 81% vs. 77% (p=0.261). 3-year actuarial OS for patients staged III/IVa/IVb with and without PET was 58% vs. 41% (p= 0.001). Conclusions: HNC patients were more likely to be upstaged with the use of PET. There was an improvement in survival in stage III/IVa/IVb patients, but no difference in survival across all stages. This likely reflects selection bias and stage migration rather than improved outcomes among individual patients.
Disparities in care for HIV patients with lung cancer.
Authors: Daniel Hartman Johnson, Marco A. Ruiz, Robert A. Ramirez
Journal: Journal of Clinical Oncology (2014)

e17566 Background: HIV patients with lung cancer appear to have an increased incidence and an overall shorter survival than HIV negative patients. Issues such as compliance with established guidelines, second and third line therapies and molecular testing have not been investigated thoroughly. Methods: We conducted a retrospective review at our institution from 2002-2013 analyzing patients with lung cancer and HIV. Frequency of molecular testing, second and third line therapy, CD4 count, HIV viral load, and survival data were included. Results: Eighteen patients were included for analysis. The median age at diagnosis was 49. Only one patient received EGFR testing; none received ALK testing. Second line and third line therapies were not offered to any patients with stage IV cancers. 64% of the patients with stage III or IV were either not treated or received palliative radiation only. 50% were immune suppressed with CD4 count <200 and 44% had viral loads > 15,000 at time of lung cancer diagnosis. The median overall survival (OS) in our entire cohort was 5.4 months compared to a 7.2 month OS seen in untreated HIV negative patients. NSCLC survival by stage compared to published survival in the general population are shown in the table. Conclusions: Our data show that HIV lung cancer patients are diagnosed at a younger age, do not get standard of care treatment, and have a poorer overall prognosis. Prior studies show that 49% of stage IV patients get 2nd line treatment, however, none of our stage IV patients with HIV received such therapy. Although it is suggested that immunodeficiency accelerates the natural history of a tumor, disparity in treatment aggressiveness contributes to the difference in lung cancer prognosis between HIV positive and negative populations. Succesful strategies proven in the general population, such as molecular testing to detect mutations amenable to targeted therapy and the use of second and third line therapy when applicable, should be encouraged in HIV patients as well. Close collaboration with HIV providers to facilitate appropriate therapy and follow up is much needed. Stage No. of patients in cohort Median survival cohort (months) Median survival non-HIV (months) Ia 1 Not yet reached 119 Ib 2 13.5 81 IIa 0 N/A 49 IIb 1 7.25 31 IIIa 4 11.5 22 IIIb 0 N/A 13 IV 9 5.25 17
Relationship between primary tumor location and prognosis in metastatic colorectal cancer patients treated with irinotecan/5-FU/leucovorin (FOLFIRI).
Authors: Qianqian Yu, Hong Qiu, Mingsheng Zhang, Xianglin Yuan
Journal: Journal of Clinical Oncology (2017)

557 Background: Clinical trials including CALGB/SWOG 80405 and FIRE-3 reveal differences in overall survival (OS) for metastatic colorectal cancer (mCRC) patients treated with targeted therapy based on primary tumor location. We assessed the impact of tumor location on prognosis in a prospective series of patients with mCRC received FOLFIRI in first-line therapy. Methods: Patients treated with FOLFIRI were consecutively recruited between November 2010 and December 2014. Follow-up information was updated in February 2016 when 77.3% of the patients were deceased. We defined the right-sided colon = cecum to transverse colon, left-sided colon = splenic flexure to sigmoid descending colon, rectum = rectosigmoid plus rectal cancer, respectively. We measured median survival using Kaplan-Meier plots and 2-year survival probability using life tables. Associations between tumor locations and treatment outcomes were estimated using a Cox proportional hazards model. Age and gender were included in adjusted Cox models to estimate the hazard ratio (HR) for death of rectal and left-sided tumors relative to right-sided tumors. Results: Right-sided cancer had a shorter median survival (13.5 vs. 20.4 months) and worse 2-year survival probability (28% vs. 39%) than left-sided and rectal cancers, however the difference was of no statistical significance no matter in unadjusted (HR = 1.002, 95% CI 0.635-1.581) or adjusted models (HR = 1.037, 95% CI 0.657-1.639). Conclusions: mCRC patients with right-sided colon got comparative survival benefit from FOLFIRI in first-line treatment to the left-sided colon and rectum. This result needs to be validated in studies with larger sample size. Clinical trial information: NCT01282658.
Prognostic value of PD-1 and PD-L1 expression in patients with high-grade urothelial carcinoma of the upper urinary tract.
Authors: Laura-Maria Krabbe, Barbara Heitplatz, Ryan C Hutchinson, Solomon L Woldu, Sina Preuss, Christopher G. Wood, Jose A. Karam, Alon Z. Weizer, Jay D. Raman, Mesut Remzi, Nathalie Rioux-Leclercq, Andrea Haitel, Marco Roscigno, Christian Bolenz, Karim Bensalah, Arthur I. Sagalowsky, Shahrokh F. Shariat, Yair Lotan, Evanguelos Xylinas, Vitaly Margulis
Journal: Journal of Clinical Oncology (2017)

358 Background: To investigate the prognostic value of PD-1 and PD-L1 expression in patients with high-grade upper tract urothelial carcinoma (UTUC). Methods: Tissue microarrays were created using 448 patients from the International UTUC collaboration who underwent extirpative surgery for high-grade UTUC and stained for PD-1 (antibody (AB): NAT105, diluted 1:250 from Ventana) and PD-L1 (AB: E1L3N prediluted from Cell Signaling). PD-1 and PD-L1 expression was assessed in a semi-quantitative fashion and any percentage of staining of the tumor cells (PD-L1) and tumor-infiltrating lymphocytes (PD-1) was considered positive. Univariate (UVA) and multivariate analyses (MVA) were performed to assess independent prognosticators of oncological outcomes. No funding was received. Results: Median age of the cohort was 69.2 years and 56.5% of patients were male. PD-L1 and PD-1 were positive in 24.1% and 37.5% of patients. PD-L1 positivity was associated with favorable pathological stage, where as PD-1 positivity was significantly associated with pelvicalyceal location, lymph node metastases, non-organ confined disease, presence of lymphovascular invasion, sessile architecture, necrosis, concomitant CIS, and history of non-muscle invasive bladder cancer. PD-L1 positivity was not significantly associated with survival outcomes. In Cox regression UVA, PD-1 positivity was associated with worse recurrence-free survival (RFS) (HR 1.5 (95%CI 1.08-2.14, p=0.016)), cancer-specific survival (CSS) (HR 1.5 (95%CI 1.07-2.19, p=0.021)), and overall survival (OS) (HR 1.5 (95%CI 1.10-1.97, p=0.009)). However in MVA, PD-1 positivity was not found to be an independent predictor of RFS, CSS or OS. Conclusions: PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and was a significant prognosticator for RFS, CSS and OS on UVA in patients treated with extirpative surgery for high-grade UTUC in a large, multi-institutional cohort. In MVA, the independent prognostic value of PD-1 was not confirmed. PD-L1 positivity was associated with lower tumor stage, but not with other pathological characteristics or survival outcomes.