tbuckley/cabot-search huggingface dataset:
Results of a phase 2a, multicenter, open-label, study of RM-1929 photoimmunotherapy (PIT) in patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC).
Authors: David M. Cognetti, Jennifer Maria Johnson, Joseph M. Curry, Frank Mott, Samith Thomas Kochuparambil, Darren McDonald, Mary J. Fidler, Kerstin Stenson, Nilesh R. Vasan, Mohammad Razaq, John P. Campana, Merrill A. Biel, Ann M. Gillenwater
Journal: Journal of Clinical Oncology (2019)

6014 Background: Patients with rHNSCC who have failed standard of care have poor prognoses and limited therapeutic options. In this study, final results are reported of a phase 2a trial of photoimmunotherapy (PIT) with a targeted drug RM-1929, consisting of the EGFR-directed antibody cetuximab conjugated to a photoactivatable dye (IRDye 700DX). Binding of the antibody-dye conjugate to cancer cells followed by photoactivation with nonthermal red light induces selective and rapid necrosis of the cancer cells, with minimal damage to surrounding tissue. Methods: A phase 2a, multicenter, open-label, study of RM-1929 PIT in patients with locoregional, rHNSCC who could not be satisfactorily treated with surgery, radiation, or platinum chemotherapy was conducted to evaluate the safety and efficacy of the drug, RM-1929. For each treatment, nonthermal red light (690 nm) was applied to the tumors 24 hours post IV infusion of the drug. Surface illumination was administered for superficial tumors and interstitial illumination via intratumoral placement of fiber optic diffusers for deep tumors. Therapeutic response was assessed using CT RECIST 1.1 by an independent blinded radiologist. Results: Thirty rHNSCC patients were enrolled. There were no dose-limiting toxicities and one Grade 1 photosensitivity reaction. Most reported AEs were mild to moderate in severity with 96.7% (29/30) of patients with Grade 1 and 83.3% (25/30) with Grade 2, respectively. There were 13 (43.3%) patients who had at least one SAE. 86% (19/22) of SAEs were deemed unlikely related to treatment, including all 3 fatal SAEs. Three SAEs were reported to be possibly/probably related to treatment (site/oral pain, tumor hemorrhage, and airway obstruction). ORR was 50% (15/30) with 16.7% (5/30) CR and 86.7% (26/30) DCR. Median PFS and OS results will be forthcoming. Conclusions: These data indicate that RM-1929 PIT treatment was generally well tolerated with majority of AEs as mild to moderate in severity. Preliminary data showed favorable response rates in a heavily pre-treated population. A global phase 3 clinical trial is currently underway. Clinical trial information: NCT02422979.
Surface programmable activation receptor (SPAR) cell platform for the rapid detection of melanoma-specific biomarkers.
Authors: Joel Lwande, Joseph D Kittle, M. Russell Williams, Shengwen Liang, Kyle McQuaid, Melissa Frenchmeyer, Yuanyuan Tang, Allison Neese, Jiangzhou Hua, Charles McBrairty
Journal: Journal of Clinical Oncology (2019)

e14263 Background: We have previously demonstrated that SPAR modified T cells effectively detect bacterial and viral pathogens. SPAR cells are engineered to express a modified T cell receptor (TCR) capable of antibody-directed signal transduction and respond with a Ca 2+ -mediated production of luminescent signal upon target detection. Here we describe the ability of SPAR cells to rapidly detect the cell surface expression of melanoma biomarkers without a requirement for extensive sample preparation. Methods: SPAR cells expressing both an engineered T cell receptor and the luminescent reporter protein aequorin were developed via the transfection of Jurkat cells with the aequorin expression vector pEF1-Aeq and an engineered TCR complex composed of mouse FcγRI fused to the CD3ζ subunit. The mFcγRI-CD3ζ receptor binds to the Fc region of full-length mouse IgG2 antibodies: SPAR cells are programmed for target detection via the addition of target-specific antibody. The ability of programmed SPAR cells to accurately detect melanoma-specific cell surface biomarkers was evaluated using whole cells from cultured mouse (B16-F10) and human (SK-Mel-28) melanoma cell lines. SPAR cells were programmed by incubation with murine antibodies directed toward the melanoma biomarkers CD133 or TRP1, then mixed with melanoma cells or K562 control cells and evaluated for signal generation. Results: SPAR cells programmed with anti-CD133 or anti-TRP1 antibody produced luminescent signal within minutes when combined with human SK-Mel-28 cells or mouse B16-F10 cells, respectively, known to abundantly express the appropriate biomarker. No signal was generated when programmed SPAR cells were incubated with K562 cells. Further studies also document cytokine production following receptor engagement. Conclusions: SPAR cells can be programmed for the rapid and specific detection of known cell surface cancer biomarkers. The Ca 2+ -dependent production of luminescent signal and cytokine release in response to TCR engagement suggests SPAR cell activation. Thus, in addition to biomarker detection the SPAR system may ultimately provide predictive insights into the potency of antibody-directed cell therapy.
Clinical features and progression pattern of T790M+ compared with T790M-EGFR mutant NSCLC.
Authors: Giulia Pasello, Alessandro Dal Maso, Martina Lorenzi, Elisa Roca, Sara Pilotto, Marianna Macerelli, Valentina Polo, Alessandro Del Conte, Giorgia Nardo, Vanessa Buoro, Daniela Scattolin, Sara Monteverdi, Loredana Urso, Elisabetta Zulato, Stefano Frega, Laura Bonanno, Stefano Indraccolo, Fiorella Calabrese, Pierfranco Conte
Journal: Journal of Clinical Oncology (2019)

e20612 Background: Acquired T790M EGFR mutation (mut) is not predictable by any clinical-pathological feature. The best time point for T790M mut detection by liquid or tissue biopsy is currently undefined. Methods: This is an observational study at 6 Italian Centers enrolling EGFR mutant NSCLC patients (pts) progressing after first/second generation EGFR TKI, between 2014 and 2018. The primary endpoint of the study was to compare clinical features in acquired T790M+ compared with T790M- cases. The secondary endpoint was to assess different progression (PD) patterns between the two groups. We also explored the PD pattern at the time of cfDNA negativity and subsequent positivity, in a subgroup of pts receiving serial liquid biopsies. Statistical analysis was performed by the Chi-square test to correlate clinical features with T790M status, and by the Kaplan-Meier estimator to evaluate median progression free (mPFS) and overall survival (mOS). Multiple logistic regression and log-rank tests were applied. Results: 219 pts were included. Median follow-up since diagnosis was 25 months. First line treatment was gefitinib (N = 119, 54%), erlotinib (N = 48, 22%) or afatinib (N = 52, 24%). In 108 (49%) cases a T790M acquired mut was detected in liquid (70), tissue (31) biopsy or both (7). Age younger than 65 years ( p= 0.05) and presence of sensitizing exon 19 deletion ( p= 0.04) were correlated with T790M mut; this association was confirmed at multivariate analysis ( p= 0.010 and p= 0.006, respectively). At the time of PD, new PD sites ( p= 0.005) and liver PD ( p&lt; 0.001) were more commonly observed in T790M+ group; at multivariate analysis statistical significance was confirmed ( p= 0.01 and p= 0.008, respectively). Longer mOS was observed in T790M+ cases at univariate (53 versus 22 months, p &lt; 0.0001) and multivariate analysis. In 13 pts undergoing serial liquid biopsies, an oligoprogressive disease was correlated with a negative test outcome, while PS/symptoms worsening, higher number of new lesions and PD sites were observed at the time of T790M positivity, although without statistical significance. Conclusions: This is the first caucasian series showing different clinical features and progression patterns of T790M+ versus T790M- EGFR mutant NSCLC.
Patient-reported outcomes of adalimumab, phototherapy, and placebo in the Vascular Inflammation in Psoriasis Trial: A randomized controlled study
Authors: Megan H. Noe, Marilyn T. Wan, Daniel B. Shin, April W. Armstrong, Kristina Callis Duffin, Zelma C. Chiesa Fuxench, Robert E. Kalb, Alan Menter, Eric L. Simpson, Junko Takeshita, Stephen K. Tyring, Abby S. Van Voorhees, Nehal N. Mehta, Joel M. Gelfand
Journal: Journal of the American Academy of Dermatology (2019)
Case 28-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, J.H. Fisher, D.L. Gang
Journal: New England Journal of Medicine (1985)

Presentation of CaseA 21-year-old woman was admitted to the hospital because of abdominal pain and vomiting.She was well until seven years earlier, when she first experienced severe midepigastric pain that radiated to the back, accompanied by vomiting. During succeeding years she had repeated bouts of similar pain and vomiting and was admitted to a nearby hospital on 9 or 10 occasions. The attacks were accompanied by leukocytosis but never by documented elevation of bilirubin or amylase levels. Each episode resolved after three to six days on a clear-liquid diet and narcotics, and she felt well in the intervals. . . .
Precision probiotic therapy enhances immune checkpoint therapy efficacy in melanoma bearing mice.
Authors: Arthur E. Frankel, Kenya Honda, Bruce Roberts, Rose Szabady, Amit Reddy, Johnny Lightcap, Steve McClellan, Sachin Kumar Deshmukh, Andrew Y. Koh
Journal: Journal of Clinical Oncology (2019)

e14195 Background: Immune checkpoint inhibitor therapy, ICT, achieves remissions in melanoma patients but factors modulating response are not well defined. Our group (Frankel et al. Neoplasia 2017) and others have identified specific gut microbiota associated with improved ICT response. Recently, we identified specific gut microbiota that induce adaptive immune responses and potentiate ICT (Tanoue et al. Nature 2019). In this study, we determined whether this predefined consortia of gut microbiota augment ICT efficacy in melanoma bearing mice. Methods: Mice (C57BL/6, 6-8wk old, female, Jackson, n = 4-12 mice) received ± antibiotic water (penicillin G 1500U/mL + streptomycin 2mg/mL) for 6 d to deplete gut microbiota. Mice were then inoculated with 10 5 B16F10 melanoma cells SQ. At d 4, 8, 12 post-tumor inoculation, 0.2 mg anti-mCTLA4 + anti-mPD1 antibodies (Bio X Cell) were administered IP. Precision probiotic therapies included Vedanta Bioscience VE800 (Tanoue et al., Nature 2019), VE804 (same as VE800 without R. lactatiformans and F. ulcerans), VE411 (four Clostridial firmicutes) (Narushima, 2014), and Lactobacillus acidophilus (ATCC 4356) probiotics were given via gavage (1x10 9 cfu) starting day +1 after tumor inoculation and 3xwkly. Loss of survival was defined as death or tumor diameters ≥ 2 cm. Tumor growth inhibition, TGI = (1- mean treated tumor volume/mean control tumor volume) x 100%. Tumor mononuclear cells were isolated for flow cytometry for murine CD4, CD8, and CD11c. Results: TGI in mice with intact gut microbiota and treated with ICT was 84 ± 4% (SEM). Pre-treatment antibiotics reduced TGI to 38 ± 11%. Groups treated with Vedanta VE800, VE804, and VE411 exhibited TGIs of 77 ± 9, 61 ± 8, and 69%, respectively, whereas treatment with Lactobacillus acidophilus achieved TGIs 57%. VE800 treated mice had significantly increased length of survival compared to mice treated with antibiotics (p = 0.0008, log-rank test). Length of survival was not significantly different between groups with intact gut microbiota and those pretreated with antibiotics and dosed with VE800 (p = 0.52, log-rank test). ICT increased tumor CD4 cells to 11% from 2% and CD8 cells to 9% from 1%., however pre-treatment with antibiotics reduced CD4 cells to 4% and CD8 cells to 1%. Conclusions: Defined consortia of gut microbiota facilitate ICT efficacy. These preclinical studies lay the foundation for optimizing the host response to ICT.
Mortality within 30 days of immunotherapy (checkpoint inhibitors) in metastatic cancer patients treated at Australian tertiary cancer center.
Authors: Hiren A. Mandaliya, Sang Kim, Gaik Tin Quah, Sandy Tun Min, James Carlton, Jack Faulkner, Christopher Oldmeadow, Girish Mallesara
Journal: Journal of Clinical Oncology (2019)

6600 Background: Cancer treatment has evolved rapidly since the advent of immunotherapy (checkpoint inhibitors). As compared to chemotherapy, immunotherapy is associated with a more favourable but distinct side effect profile. Mortality within 30 days of chemotherapy in cancer patients has been accepted as a clinical indicator of preventable harm and used as an auditing tool for clinical practice and improving quality of life. This should be investigated in the current era of immunotherapy, as it has been the standard treatment for advanced melanoma, lung cancer, renal cell cancer and others. Methods: We conducted a retrospective study on patients with advanced cancer treated with immunotherapy and died within 30 days of treatment. Clinical data on patients treated with immunotherapy at Calvary Mater Newcastle between 2006 and 2018 was collected. Data were compared with 30-day mortality statistics of chemotherapy. Results: A total of 601 metastatic cancer patients received immunotherapy agents (Pembrolizumab, Nivolumab, Ipilimumab, Atezolizumab, Tislelizumab and MSB0011359C) on 5022 occasions. Seventy-six (12.6%) patients died within 30 days of receiving immunotherapy. Median age was 68 years (35-90). Melanoma was the most prevalent cancer type (63%) followed by lung (20%). Forty-seven (47%) of patients received immunotherapy as first-line treatment and 39% as second-line. Patients died within 30 days received an average 2 (1-16) immunotherapy doses. A quarter of patients had ECOG 3 and ECOG 4 before last dose. Majority of deaths were related to disease (86%). Nearly 80% of patients died in hospital. One patient died due to treatment-related pneumonitis. In univariate analysis, there was no association between mortality and patients’ demographic variables such as age, sex, BMI, cancer type, ECOG performance status, immunotherapy agent and prior treatment. Conclusions: To our knowledge, this is the first ever real-world data on 30-day mortality after immunotherapy in advanced cancer. Thirty-day mortality rates were comparable to published data on patients treated with chemotherapy. Results emphasise significance of careful selection of advanced cancer patient for immunotherapy. Due to small sample size, the power to detect a significant association between patients demographics and survival is reduced.
Health-related quality of life (HRQL) in VERTU: A randomized phase II trial of veliparib (V), radiotherapy (RT), and temozolomide (TMZ) for newly diagnosed MGMT unmethylated (uMGMT) glioblastoma (GBM).
Authors: Hao-Wen Sim, Elizabeth Barnes, Zarnie Lwin, Mark Rosenthal, Helen Wheeler, Eng-Siew Koh, Matthew C. Foote, Lauren Fisher, Robyn Leonard, Merryn Hall, John Simes, Mustafa Khasraw
Journal: Journal of Clinical Oncology (2019)

2042 Background: The VERTU trial (ANZCTR #ACTRN12615000407594) compared Arm A (standard of care) = RT (60Gy/30 fractions) + TMZ (75mg/m 2 daily) followed by TMZ (150–200mg/m 2 D1–5) every 28 days for 6 cycles vs Arm B (experimental arm) = RT (60Gy/30 fractions) + V (200mg PO BID) followed by TMZ (150–200mg/m 2 D1–5) + V (40mg PO BID, D1–7) every 28 days for 6 cycles in pts with newly diagnosed centrally determined uMGMT GBM. To ensure that veliparib was not associated with clinical detriment, serial HRQL assessments were performed for comparison as a secondary objective. Methods: Pts completed the EORTC quality of life core questionnaire (QLQ-C30) and brain cancer module (BN20) every 4 weeks (w) (baseline: w0; concurrent: w4,8; adjuvant: w10,14,18,22,26,30). Based on relevance to GBM patients, 5 HRQL scales (global health [GH], physical functioning [PF], social functioning [SF], motor dysfunction [MD] and communication deficit [CD]) were pre-selected for primary analysis. Maximum change from baseline score (clinically relevant deterioration/improvement defined as ≥10-point change) during the progression-free period, and deterioration-free survival (time to deterioration/progression/death) were evaluated. Results: Patient characteristics were well-matched (Arm A: N = 41, median age = 62, male = 68%, ECOG 0 = 66%, macroscopic resection = 88%; Arm B: N = 84, median age = 60, male = 70%, ECOG 0 = 65%, macroscopic resection = 86%). Almost all completed at least one HRQL assessment (98%). HRQL assessments during the progression-free period were completed in 87% (Arm A) and 90% (Arm B) of cases. For Arm A vs B, the proportion of patients who experienced a deterioration in GH (59% vs 64%, p = 0.69), PF (53% vs 53%, p &gt; 0.99), SF (46% vs 53%, p = 0.56), MD (63% vs 58%, p = 0.70) and CD (45% vs 46%, p &gt; 0.99) were similar. Deterioration-free survival was not statistically different for any HRQL item. Conclusions: The addition of veliparib to standard of care for newly diagnosed uMGMT GBM does not appear to compromise HRQL. This would support the primary efficacy analysis of the VERTU trial. Clinical trial information: ACTRN12615000407594.
Clinically significant discrepancy between clinical and pathologic stage of early-operable cervical cancer.
Authors: Jennifer Gibbs, Victoria Hastings, Nikita Malakhov, Katherine Economos, Margaux J Kanis
Journal: Journal of Clinical Oncology (2019)

5526 Background: The cornerstone of the management of cervical cancer (CC) traditionally relies on clinical examination assessment (CE) of tumor size (TS) and local extension of disease. Previous reports demonstrate poor accuracy of CE, with the most common discrepancy being failure to identify parametrial involvement (PI). The goal of this study is to determine the accuracy of CE in comparison to final pathology (FP) in early operable CC. Methods: This is a multi-center retrospective review of patients with early CC (FIGO stage IB1, IIA1). Data on age, race, histology, stage, CE findings, FP report and receipt of adjuvant radiation therapy (RT) were collected. CE findings included TS, PI and vaginal involvement (VI). CE of TS, PI, and VI were compared to FP. Subanalysis was also conducted based on TS ( &lt; or ≥ 2cm) and location of tumor (exophytic vs endophytic). Analysis was performed using paired-T and Cohen’s Kappa tests. Results: Final analysis included 135 patients. Mean age was 52.6 years. The majority of patients had squamous cell carcinoma (72.6%). Overall, there was a significant difference between CE of TS compared to FP; mean error of 1.22 cm (p &lt; 0.0001). In those with tumors ≥ 2cm the mean error was 1.28 cm (p &lt; 0.0001). No significant discrepancy was observed in tumors &lt; 2 cm (mean error: 1.10cm; p = 0.5). CE of TS of endophytic tumors was poor (mean error 1.68cm; p = 0.004) compared to exophytic tumors (mean error: 1.12 cm; p = 0.693). There was no significant difference in the identification of VI between CE and FP (3.7% vs 8.89%; p = 0.067). No patients with PI on CE were included in this analysis. However, 14.07% of patients were found to have PI on FP (p &lt; 0.0001). There was no difference in the accuracy CE of TS between non-obese ( &lt; 30 kg/m 2 ) and obese patients (≥30 kg/m 2 ), mean error 1.13 and 1.3, respectively (p = 0.061). As a results of FP, 55 patients (40.7%) received adjuvant RT and 38 patients (28.14%) were upstaged from IB1 to IB2. Of these 38 patients, 36 (94.7%) went on to receive adjuvant RT. Conclusions: CE of TS and PI is inaccurate, especially in tumors ≥ 2cm and endophytic tumors. This suggests imaging should be strongly encouraged, particularly in the setting of the updated FIGO 2018 staging system and recent debate over surgical approach.
Trifluridine/tipiracil (FTD/TPI) in patients (pts) with metastatic gastroesophageal junction cancer (mGEJC): Subgroup analysis from TAGS.
Authors: Wasat Mansoor, Hendrik-Tobias Arkenau, MARIA ALSINA, Kohei Shitara, Mohamedtaki Abdulaziz Tejani, Peter C. Thuss-Patience, Sinead Cuffe, Mikhail Dvorkin, David Park, Takayuki Ando, Marc Van Den Eynde, Giordano D. Beretta, Alberto Zaniboni, Toshihiko Doi, Josep Tabernero, David H. Ilson, Lukas Makris, Sandra McGuigan, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2019)

4038 Background: The incidence of GEJC is increasing in North America and Europe, especially among white men. Many pts present with metastatic disease or relapse locally or systemically after resection of early-stage disease. The global phase 3 study TAGS (NCT02500043) demonstrated the efficacy and safety of FTD/TPI in previously treated pts with metastatic gastric cancer (mGC)/mGEJC. Here we report results in the mGEJC subgroup from TAGS. Methods: Pts with mGC/mGEJC treated with ≥2 prior chemotherapy regimens were randomized (2:1) to receive FTD/TPI (35 mg/m 2 BID on days 1–5 and 8–12 of each 28-day cycle) or placebo, plus best supportive care. A preplanned efficacy and safety analysis was performed in pts with mGEJC. Results: Of 507 randomized pts, 145 (29%) had GEJC as the sole primary disease site (FTD/TPI, 98/337; placebo, 47/170). Of pts with mGEJC, 85% were male and 83% were white (overall population, 73% and 70%). Baseline characteristics were generally balanced for pts with mGEJC across treatment groups, except for fewer pts having prior gastrectomy (40% vs 55%) and more pts having received ≥3 prior regimens (74% vs 66%) in the FTD/TPI group than in the placebo group. FTD/TPI had an efficacy benefit in pts with mGEJC, and the FTD/TPI safety profile was similar in this subgroup and the overall population (table). Conclusions: FTD/TPI showed a manageable safety profile and efficacy benefit in pts with mGEJC in the TAGS trial, despite heavier pretreatment of the FTD/TPI than the placebo group. Clinical trial information: NCT02500043. [Table: see text]
Combination of statin/vitamin D and metastatic castration-resistant prostate cancer (mCRPC): A post-hoc analysis of two randomized clinical trials.
Authors: Guillermo de Velasco, David Lora, Alberto Carretero-Gonzalez, Maria Cruz Martin Soberón, Juan Manuel Manuel Sepulveda Sanchez, David Lorente, Daniel E. Castellano
Journal: Journal of Clinical Oncology (2019)

6617 Background: Retrospective database studies have suggested that statins and vitamin D have a positive impact on prostate cancer survival and specifically in mCRPC patients (pt). Methods: We conducted a post-hoc analysis of individual pt data of mCRPC pts treated with abiraterone (AA) and/or Prednisone (P) on two randomized phase III clinical trials COU -AA-301 and COU-AA-302 to analyze the impact of statins and vitamin D in overall survival (OS). Statistical analyses were performed using the Kaplan Meier method and Independent predictors were investigated using Cox regression analysis. This study, carried out under YODA Project #2016-1136, used data obtained from the Yale University Open Data Access Project. Results: These two studies included 2280 patients (1340 treated with AA/P and 640 with P). Use of Statin + vitamin D was associated with a 38% reduction in mortality in the postdocetaxel setting and 32% in the predocetaxel setting in patients treated with abiraterone (Table 1 and 2). No significant reduction in the rate of skeletal-related events was seen in patients treated with vitamin D or statins. Conclusions: To our knowledge this is the first report suggesting the impact of vitamin D+statin in mCPRC treated with abiraterone. The potential benefits of vitamin D do not seem to be secondary to concomitant statin use in this population. Further studies are needed to confirm these results. [Table: see text][Table: see text]