tbuckley/cabot-search huggingface dataset:
Insurance disparity in cause-specific mortalities: A SEER study on early stage, non-elderly NSCLC cancer survivors.
Authors: Changchuan Jiang, Qian Wang, Wuyang Yang, Lei Deng, Zhengrui Xiao, Yuzhou Liu, Gabriel Albert Sara
Journal: Journal of Clinical Oncology (2018)

8538 Background: Lung cancer is the leading cause of cancer-related death in the US. Non-elderly, early stage (stage I&II) non-small cell lung cancer (NSCLC) patients have the most promising prognosis with appropriate treatments. Studies have shown uninsured and elderly patients on Medicaid being less likely to receive guideline-concordant therapy and thus with higher mortality. However, it remains unknown how insurance status influences cause-specific survival in non-elderly NSCLC patients, and whether disparity of care is improved in this cohort after ACA. Methods: Surveillance, Epidemiology, and End Results Program from 2007-2014 was used to identify NSCLC patients on stage I and II on diagnosis. Elderly patients ( > 65 years) were excluded. Demographic and lung cancer characteristics including age, gender, race, education, income, insurance status, tumor grade/stage and treatment were analyzed. Competing risk analysis was conducted using SAS9.4. Results: A total of 13,898 patients were included. After adjusting for socio-demographic factors, tumor grade and treatment, Medicaid and non-insured were associated with higher lung cancer mortality (HR: Medicaid 1.30 (1.17-1.44), non-insured 1.26 (1.05-1.50)). Patients with any Medicaid sustain the highest mortality for cardiovascular diseases(CVD) and non-cancer respiratory diseases(NCR) across different insurance status (CVD HR: Medicaid 2.17 (1.57-2.99), non-insured 1.37 (0.74-2.56); NCR HR: Medicaid 2.46 (1.76-3.43), non-insured 0.73 (0.30-1.81)). Diagnosis after ACA was associated with lower lung cancer specific mortality but not related to CVD or NCR mortality. No effect modification was found for diagnosis after ACA on any specific cause mortality. Conclusions: Despite ACA and Medicaid expansion in 2010, Medicaid and non-insured patients have higher cancer mortality compared with insured in early-stage NSCLC patients. Furthermore, non-elderly, early-stage NSCLC cancer survivors with Medicaid have remarkably higher CVD mortality compared to private insured survivors even without any insurance, which may reflect the disparity in health literacy, primary care, and cancer survivorship care access.
REZOLVE (ANZGOG-1101): A phase 2 trial of intraperitoneal (IP) bevacizumab (bev) for recurrent ascites in advanced, chemotherapy-resistant, epithelial ovarian cancer (CR-EOC).
Authors: Katrin Marie Sjoquist, Linda R. Mileshkin, Sumitra Ananda, Catherine M. Shannon, David Bowtell, Sonia Yip, David Espinoza, Jeffrey C. Goh, Michelle L. Harrison, Magdalena Plebanski, Val Gebski, Martin R. Stockler, Karen Livingstone, Monica Tang, Michael Friedlander
Journal: Journal of Clinical Oncology (2018)

10097 Background: We sought to determine the safety and activity of IP bev for recurrent malignant ascites requiring repeated paracenteses, a major problem for women with CR-EOC. Methods: Eligible women had CR-EOC and symptomatic, malignant ascites that recurred within 28 days of their last paracentesis (P-1). Participants had IP bev 5mg/kg instilled at the end of their first therapeutic paracentesis on study (P0). Additional doses of IP bev were allowed at each subsequent paracentesis (P1, P2 etc) if the interval from the last dose was 42 days or more. The primary objective was to determine the proportion alive and free of repeat paracentesis at 42 days. Safety and quality of life were secondary outcomes. Serial samples of blood and ascites were collected for translational studies. The hypothesis was that IP bev would be worthy of further study if the proportion alive and free of repeat paracentesis at 42 days was 54% or more, but not if it was 20% or less. Results: We recruited 24 participants with a median age of 67 years (range 38 – 86), median of 4.5 lines of prior systemic treatment (range 1 – 12), and ECOG performance status of 0-1 in 9, and 2-3 in 15. The numbers of doses of IP bev administered were 1 in 13 participants, 2 in 5, 3 in 2, 4 in 1, and 5 in 1. The proportion free of paracentesis at 42 days using competing risk analysis was 77% (95% CI 58 to 92). Median time from P0 to P1 or death (puncture-free survival) was 48 days (range 8 to 248 days). Median Paracentesis free interval (P0 to P1 or death) was 4.29 (95% CI 2.4 to 5.8 ) times higher following first dose of IP bevacizumab compared with the time between paracenteses prior to study entry (P-1 to P0). Grade 3-4 AEs (number of participants, regardless of attribution) included abdominal pain (4), distension (4), small bowel obstruction (3), nausea (2), fatigue (2), and grade 3 bowel perforation (1). Conclusions: IP bev was safe, active, and warrants further study as a palliative intervention for recurrent ascites in CR-EOC. Clinical trial information: 12611000801910.
Third- and fourth-line treatment in patients with RCC: Results of a prospective multicentric non-randomised study (IVOIRE study).
Authors: Eric Voog, Boris Campillo-Gimenez, Claude El Kouri, Frank Priou, Brigitte Laguerre, Florence Joly, Jacques Merrer, Valérie Delecroix, Annick Le Rol, Remy Delva, Jean-pierre Malhaire, Chaza Elhannani, Christian Pfister, Frederic Rolland, Oana Cojocarasu, Isabelle Cumin, Erik Monpetit, Delphine Deniel Lagadec, Fanny Marhuenda, Francoise Grude
Journal: Journal of Clinical Oncology (2016)

4567 Background: Sequential targeted therapy is standard in patients (pts) with clear-cell renal carcinoma (RCC). Clinical Practice Guidelines exists only for first and second lines (ESMO recommendations). Exploratory recommendations for next treatments (ttt) have been proposed according to their risk (MSKCC). In line 3, pts without prior everolimus were proposed to receive it. Pts who have failed 2nd line ttt with everolimus were proposed to rechallenge TKI only if they experimented a disease control > 6 months in 1st line. For line 4, TKI or everolimus were rechallenged according to the same previously quoted criteria. Methods: A prospective multicentric study has included pts treated according to these guidelines. The objectives were overall survival and for each line best response (RECIST), disease control time (time from day 1 of treatment to the day before the next ttt) and grade 3/4 toxicity. Results: 270 advanced or metastatic renal cancer pts have been included in 17 French centers between Sept 1st, 2011 and Sept 1st, 2014: 73% men; median age 65.5 years [35-90]; Clear RCC: 86%; grade III-IV Führmann: 54%. Results are summarized in table. Poor risk pts are not presented here. 39% and 21% of pts receiving a line 1 were able to receive a line 3 and 4 and clinical benefit remained high : 54% and 36% respectively for TKI and 51% for everolimus (L3). OS was 59 months [50-73]. More data will be shown at the meeting. Conclusions: For pts who responded > 6 months to TKI, rechallenging the same ttt in a subsequent line could provide high clinical benefit with acceptable toxicity. TTT Criteria L1 n = 270 L2 n = 195 L3 n = 106 L4 n = 58 TKI n 248 87 66 33 Best response CR+RP : 46% SD : 30 % PD : 16 % NA : 8 % CR+RP : 28 % SD : 38 % PD : 20 % NA : 14 % CR+RP : 15 % SD: 39 % PD: 35 % NA : 11 % RP : 12 % SD: 24 % PD: 30 % NA : 34 % Median DCT Months [Q1-Q3] 12.9 [6.4-23.1] 7.1 [3.4-13.4] 6.2 [3.2-12.1] 3.7 [1.4-9.4] Everolimus n 5 101 28 8 Best response SD : 4 ptsPD : 1 pt RP : 9 % SD: 44 % PD: 26 % NA : 21 % RP : 4 % SD: 46 % PD: 36 % NA : 14 % SD: 3 ptsPD: 2 pts NA : 3 pts Median DCT Months [Q1-Q3] Not done 6.9 [2.8-12.4] 5.3 [2.0-8.1] 1.6 [0.8 - 4.2] Others ttt n 17 7 12 17 BR: Best Response; Not Assessable (NA) = ongoing treatment/imaging not done; DCT: Disease Control Time ; Q1/3 : 1st /3rd Quartile.
Effect of MiR-137 and MiR-496 on Del-1 and triple negative breast cancer progression.
Authors: Jae-Hwan Jeong, Soo Jung Lee, Jeeyeon Lee, Jin Hyang Jung, Ho Yong Park, Ji-young Park, Seung Hee Kang, Yee Soo Chae, Jong Gwang Kim
Journal: Journal of Clinical Oncology (2017)

e23058 Background: Although Del-1 was recently proposed as a new biomarker for early breast cancer in our previous studies, the mechanisms of Del-1 expression are barely understood. In the current study, we selected two microRNAs (miR-137 and - 496), potentially affecting Del-1 expression in breast cancer and examined their impact on Del-1 expression in a variety of breast cancer cell lines to identify their potential role in Del-1 expression and thereby breast cancer development or progression. . Methods: Del-1 mRNA and miR-137/– 496 levels were measured by qRT-PCR among breast epithelial (MCF10A) and cancer cells (MDA-MB-231, MCF7, SK-BR3 and T-47D). The effects of miR-137/– 496 on cell proliferation and invasion were detected using MTT, wound healing and Transwell assays. Furthermore, luciferase reporter assay was used to identify the direct regulation of Del-1 by miR-137 or – 496 in MDA-MB-231 cells. Plus, we analyzed the expressions of miR-137 or – 496 and Del-1 mRNA from 20 patients with triple negative early breast cancer. Results: miR-137 and – 496 levels were low in all breast cancer cell lines. As Del-1 mRNA expression was remarkably higher in MDA-MB-231 compared to the other breast cancer cell lines, further functional analyses were done with MDA-MB-231 representing triple negative breast cancer subtype. Both miR-137 and miR-496 were revealed to directly bind at the 3’-UTR of Del-1. Del-1 by Luciferase reporter assay and Del-1 expression was upregulated by inhibitors and reversed by both mimics of both miR-137 and miR-496. Furthermore, both miR-137 and miR-496 were also demonstrated to inhibit cell proliferation, migration and invasion of MDA-MB-231, suggesting that these miRNAs affect cancer progression via Del-1. MiR-137 and miR-496 were remarkably down-regulated in 7 out of 12 triple negative breast cancer tissues, in particular with high Ki67 and high histologic grade. Conclusions: Although Del-1 was recently introduced as a new biomarker for triple negative breast cancer, the mechanisms of Del-1 expression were barely identified. The current study firstly demonstrated that microRNA 137 and 496 are involved in Del-1 regulation by binding at Del-1 gene, affecting cancer progression by altering Del-1 expression.
Incidence of intrathoracic (IT) metastases detected by <sup>68</sup>Ga-PSMA-11 PET in early stage prostate cancer (PC).
Authors: Rahul Raj Aggarwal, Matthew R. Cooperberg, Hao Gia Nguyen, Eric Jay Small, Charles J. Ryan, Felix Yi-Chung Feng, Albert Chang, Kirsten L Greene, Peter Carroll, Tom Hope
Journal: Journal of Clinical Oncology (2017)

5056 Background: Standard imaging in early stage PC has focused on detecting metastases (mets) within the abdomen and pelvis. The incidence of IT mets (lung, mediastinal, or supraclavicular) mets is unknown, but presumed to be negligible. Whole body 68 Ga-PSMA PET has greater sensitivity compared to conventional imaging, affording the opportunity to estimate the incidence of IT mets. Methods: Newly diagnosed or biochemically recurrent (BCR) PC patients (pts) with apparent localized disease on standard imaging were enrolled on a prospective study of 68 Ga-PSMA PET imaging between June 2015 and January 2017 and were analyzed for incidence of IT mets. Positive lesions were defined as uptake higher than blood pool. When appropriate, patients underwent confirmatory biopsy of the PSMA-avid IT lesions. Results: 364 pts underwent 68 Ga-PSMA PET imaging, including 121 (33%) pts with newly diagnosed PC and 243 (67%) pts with BCR. 145 pts (40%) had at least 1 PSMA-avid metastasis. PSMA-avid IT mets were detected in 20 pts (5.5% of overall cohort; 13.8% of those with ≥ 1 PET-positive mets), including 3 newly diagnosed (2.5%) pts and 17 (7.0%) pts with BCR. 9 of 20 pts (45%) had IT mets as the only detectable site of metastasis on PET. Biopsy of the PSMA-avid IT lesion was found to harbor PC in 5/5 patients (100%). Sites of detection included: supraclavicular node, n = 9 (2.5%); mediastinal node(s), n = 10 (3.6%), and visceral lung, n = 4 (1.0%). In the entire study cohort of 364 pts, 43% of pts had a Gleason Score ≥ 8 at diagnosis, median PSA was 4.87 ng/mL (range: 0.04 – 83.7), and the median PSA doubling time was 6.2 months (range: 0.4 – 78.3) in patients with BCR. There were no significant differences in PSA, PSA doubling time, Gleason grade, or stage between patients harboring IT metastases vs. those who did not. Conclusions: IT mets are detected by 68 Ga-PSMA PET imaging at an appreciable frequency in early stage PC with apparent localized disease by conventional imaging, which may significantly impact management in these cases. Further studies are warranted to validate these findings and determine the optimal strategy for the detection and treatment of supradiaphragmatic metastases in newly diagnosed and biochemically recurrent PC. Clinical trial information: NCT02918357.
Optimal treatment sequence for untreated EGFR-mutant NSCLC with brain metastases.
Authors: Eriko Miyawaki, Hirotsugu Kenmotsu, Hideyuki Harada, Koichi Mitsuya, Nobuaki Mamesaya, Takahisa Kawamura, Haruki Kobayashi, Kazuhisa Nakashima, Shota Omori, Kazushige Wakuda, Akira Ono, Tateaki Naito, Haruyasu Murakami, Masahiro Endo, Yoko Nakasu, Toshiaki Takahashi
Journal: Journal of Clinical Oncology (2018)

e14021 Background: Currently, whole-brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) or surgery can be combined with EGFR-tyrosine kinase inhibitors (TKIs) for EGFR-mutant non-small cell lung cancer (NSCLC) with brain metastases (BM). SRS is standard therapy for patients with 1–4 BM. This study aimed to determine the best treatment sequence for EGFR-mutant NSCLC with BM. Methods: We retrospectively evaluated EGFR-mutant NSCLC cases with BM from a single site. Cases were divided into two groups by upfront therapy: EGFR-TKI (TKI-group) or local therapies (LT-group). Overall survival (OS) was measured from the start of treatment; progression-free survival (PFS) was from the start of EGFR-TKI. Results: Among 118 patients, 66% received upfront EGFR-TKI, and 34% received WBRT (n = 20), SRS (n = 16) or surgery (n = 4) followed by EGFR-TKI. Clinical characteristic were as follows (LT-group/TKI-group): median age, 68/68 years; female, 65%/77%; PS 0–1, 68%/76%; activating EGFR mutation, 85%/99%, none of which were significantly different between the groups. The LT-group more frequently had symptomatic BM (45% vs 9%) and BM diameters ≥1 cm (75% vs 42%), and less frequently had extracranial metastases (75% vs 95%). The number of patients with 1–4 BM was not different (43% vs 58%, p = 0.12). All patients with 1–4 BM in the LT-group, except for surgical cases, received SRS (n = 13). Among those with ≥5 BM, most (n = 20, 87%) received WBRT. There was no significant difference in OS between the groups (median OS: 25 vs 24 months, HR: 0.82, 95%CI: 0.52–1.26); PFS was also similar in the groups. Multivariable analysis of OS showed that PS, activating EGFR mutation and asymptomatic BM were significant prognostic factors, while the number and size of BM were not. In cases with 1–4 BM, LT-group showed significantly better OS than the TKI-group (median OS: 38 vs 24 months, HR: 0.52, 95%CI: 0.26–0.96). There was no difference in OS between the groups for patients with ≥5 BM. Multivariable analysis showed that upfront local therapy yielded significantly better OS for patients with 1–4 BM. Conclusions: Although upfront local therapies did not show survival benefits for multiple BM, upfront SRS followed by EGFR-TKI is the optimal treatment sequence for limited BM.
Effects of rifampin on the pharmacokinetics of copanlisib, a novel pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor in cancer patients.
Authors: Anna Spreafico, Michael B. Sawyer, Lillian L. Siu, Funan Huang, Susanne Reschke, Chenghua Xia, Zhaoping Yan, Isabelle Genvresse, Galia Cisternas, Andrea Kelly, Fatima Khan, Stefanie Reif, Camille Granvil
Journal: Journal of Clinical Oncology (2018)

e14559 Background: Copanlisib, an iv pan-PI3K inhibitor recently approved for treatment of relapsed follicular lymphoma, is metabolized by CYP3A4 ( > 90%) in vitro. Here, we report effects of rifampin, a strong CYP3A and P-gp transporter inducer, on the pharmacokinetics (PK) of copanlisib and its active minor metabolite (M-1) (NCT02253420). Methods: A total of 12 subjects with advanced solid tumors received the approved dose of copanlisib (60 mg IV) on C1D1 and 15. Rifampin (600 mg p.o. daily) was administered from C1D10 to C1D21 for a total of 12 days (d). Blood samples were collected up to 8 days on C1D1 and 15. Point estimates (least squares [LS] means ratio) of AUC and Cmax and corresponding 90% CIs were calculated. Results: Following co-administration of rifampin for 12 d with a single IV dose of copanlisib, the geometric LS mean for Cmax and AUC was reduced by 14 and 56%, respectively, compared to copanlisib alone (Table). Copanlisib clearance increased by 2.3-fold from 22.6 to 51.4 L/h with co-administration of rifampin. Copanlisib geometric mean half-life value decreased from 39 h (copanlisib alone) to 17 h (copanlisib plus rifampin). Geometric mean Cmax for copanlisib minor metabolite M-1 was 4-fold higher with rifampin vs. copanlisib alone. Geometric LS mean AUC for M-1 was 0.614 (39% reduced) (90% CI: 0.504 to 0.747) when compared to copanlisib alone. Treatments were well tolerated. Conclusions: Co-administration of rifampin decreased copanlisib exposure (AUC) and increased its principal metabolite M-1, consistent with the proposed metabolic pathway. Concomitant use of copanlisib with strong inducers of CYP3A4 should be avoided. Clinical trial information: NCT02253420.Table: PK of copanlisib and its metabolite following concomitant administration of rifampin Analyte Parameter Copanlisib (Reference) Geometric Mean Copanlisib + Rifampin (Test) Geometric Mean LS Geometric Mean Ratio (90%CI) (Test/Reference) Copanlisib Cmax (µg/L) 503 431 0.857 (0.731, 1.003) AUC(0-168) (µg*h/L) 2542 1151 0.459 (0.389, 0.542) AUC (µg*h/L) 2657 1167 0.439 (0.367, 0.524) M-1 metabolite Cmax (µg/L) 14.4 55.5 3.856 (3.411, 4.368) AUC(0-168) (µg*h/L) 510 371 0.641 (0.533, 0.770) AUC (µg*h/L) 529 370 0.614 (0.504, 0.747)
Immune checkpoint inhibitor (anti PD-1/PD-L1 antibody activity in dedifferentiated endometrial carcinoma.
Authors: Ruriko Ono, Kentaro Nakayama, Hiroaki Itamochi, Kohei Nakamura, Hiroki Sasamori, Hitomi Yamashita, Tomoka Ishibashi, Masako Ishikawa, Kaori Ohnishi, Toshiko Minamoto, Kouji Iida, Noriyoshi Ishikawa, Yoshiro Otsuki, Satoru Kyo
Journal: Journal of Clinical Oncology (2018)

e17565 Background: Dedifferentiated endometrial carcinoma is defined as the undifferentiated carcinoma admixed with well-differentiated endometrioid carcinoma (Grade 1 or 2). Dedifferentiated endometrial carcinoma has a poor prognosis as compared with endometrioid adenocarcinoma of Grade 3, but it is often associated with loss of mismatch repair (MMR) proteins, which seen in microsatellite instability (MSI) type endometrial cancer with good prognosis. In recent study, effectiveness of immune checkpoint inhibitor therapy is related to loss of MMR proteins, so we examined the loss of MMR proteins proteins and the expression of PD-1 / PD-L1 in dedifferentiated endometrial carcinoma. Methods: Expression of MMR proteins (MLH1, PMS2, MSH2, and MSH6), CD8, PD-L1, and PD-1 were evaluated by immunohistochemistry in 17 cases of dedifferentiated endometrial carcinoma. Results: Since the undifferentiated region and the well-differentiated region showed different staining results, we evaluated them separately. In the undifferentiated region, 9 cases (53%) were deficient in MMR proteins and 9 cases (53%) were expressed PD-L1. PD-L1 expression were significantly higher in the MMR proteins negative group compared to the all MMR proteins positive group (p = 0.026).In the well-differentiated region, 8 cases (47%) were deficient in MRR proteins and there was no case of PD-L1 expression. 7 cases (63%) were expressed PD-1 on tumor infiltrating lymphocytes (CD8+). Conclusions: Our results showed that immune checkpoint inhibitors (anti PD-1/PD-L1 antibody) could be effective in dedifferentiated endometrial carcinoma and the presence of MSI may be a biomarker for good response to PD-L1 immunotherapy in dedifferentiated endometrial carcinoma.Interestingly, even within the same tumor, staining result is different at the undifferentiated and the well-differentiated regions, and PD-L1 was expressed only in the undifferentiated region. This suggest that DEAC has intra-tumor heterogeneity, and acquires an immune escape mechanism in the process of dedifferentiation.
Cost effectiveness of carfilzomib (CAR), ixazomib (IXA), elotuzumab (ELO), or daratumumab (DAR) with lenalidomide and dexamethasone (LEN+DEX) vs LEN+DEX in relapsed/refractory multiple myeloma (R/R MM).
Authors: Nimer Alsaid, Ali McBride, Amit Balkrishna Agarwal, Abdulaali Mutairi, Faiz Anwer, Ivo Abraham
Journal: Journal of Clinical Oncology (2017)

8030 Background: CAR, IXA, ELO, and DAR in triplet combination with LEN+DEX have shown superior efficacy over LEN+DEX in R/R MM, but their comparative efficacy and cost effectiveness has not been estimated. Methods: Network meta-analysis [NMA] and Bücher method were used to indirectly estimate comparative progression-free survival (PFS) efficacy. A 2-state Markov model (progression-free, progressed or death) was specified. Inputs included: cost of chemotherapy, administration, adverse events (AE) management, disease monitoring; utilities for health states; and disutilities for AEs. Incremental cost effectiveness (ICER) and cost utility ratios (ICUR) were calculated for resp. PFS life years (PFS LY) and quality adjusted life years (PFS QALY) gained in base case and probabilistic sensitivity analyses (PSA). Results: NMA and Bücher indirect comparison methods yielded similar PFS hazard ratios (HR), revealing superiority of DAR+LEN+DEX over other triplets in terms of PFS (Table). Using the exponential distribution to fit PFS data, our cost effectiveness analysis indicated that all 4 triplet regimens were associated with additional PFS LY and QALY gained over LEN+DEX at additional cost. DAR+LEN+DEX was associated with the greatest PFS LY and QALY gained at the lowest relative cost, yielding superior ICER and ICUR estimates compared to other triplet regimens. Conclusions: The superior PFS efficacy of DAR+LEN+DEX is associated with positive cost effectiveness and cost utility in the setting of R/R MM. [Table: see text]