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  • American Society of Clinical Oncology (ASCO)  (4)
  • 1
    Online Resource
    Online Resource
    A phase I study of veliparib incorporated into front-line platinum based cheotherpy and bevacizumab in epithelial ovarian cancer (NCT00989651): A GOG/nrg trial.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 5523-5523
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 5523-5523
    Abstract: 5523 Background: Veliparib, a poly-(ADP-ribose)-polymerase inhibitor, increases anti-tumor activity when combined with platinum chemotherapy and has monotherapy activity in BRCA deficient tumors. This study was done to determine the recommended phase II dose (RP2D) of veliparib in combination with front line treatment for epithelial ovarian cancer (EOC). Methods: Eligible patients had newly diagnosed, stage II-IV EOC. Six regimens were evaluated, 3 variations of chemo delivery with either continuous (D1-21) or intermittent (days-2-5) veliparib BID. Chemo included 1: IV q3week carboplatin (C) (AUC 6) and paclitaxel(T) (175mg/m2); 2, IV q3week C (AUC 6) and weekly T(80mg/m2); and 3, IV T (135mg/m2, day 1), IP cisplatin (75mg/m2, day 1 or 2) and IP T (60mg/m2, day 8). Bevacizumab 15mg/kg started cycle 2 and continued as monotherapy cycles 7-22. A 3+3 dose escalation design evaluated dose-limiting toxicities (DLTs) in cycles 1 and 2. Once 〈 2/6 patients experienced a DLT, that dose level was expanded to evaluate feasibility over 4 cycles. Results: The study accrued 424 treated patients. For regimen 1, continuous (Reg1c) the maximum tolerated dose (MTD) was 250mg veliparib BID but the feasible dose was found to be 150mg BID. For regimen 1, intermittent (Reg1i) the MTD and feasible dose were 400 and 250mg BID respectively. For Reg2c the MTD and feasible dose were the same at 150mg BID. For Reg2i the MTD and feasible dose were 250 and 150mg BID respectively. For Reg3c the MTD and feasible dose are both 150mg BID and for Reg3i, the MTD was 400mg BID and the feasible dose felt to be 300mg BID. Median PFS by residual disease and BRCA status is: (Positive residual disease) 14.6, 19.1 and 16.9 months for BRCA+, BRCAwt and BRCA ukn respectively. For no gross residual disease the PFS is NR, 34.2 and 24.5 months respectively. Conclusions: Given the difficulty with toxicity not defined as a DLT, the RP2D for all regimens is veliparib 150mg BID. This data informed the dose that moved into the phase III trial GOG 3005/Velia: NCT02470585. Velia also incorporated maintenance veliparib instead of maintenance bevacizumab among all high grade serous patients (BRCA+ and wt). These results will determine utilization of veliparib in this space. Clinical trial information: NCT00989651.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.5523
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Safety and tolerability of veliparib, an oral PARP inhibitor, and M6620 (VX-970), an ATR inhibitor, in combination with cisplatin in patients with refractory solid tumors.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 3067-3067
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 3067-3067
    Abstract: 3067 Background: M6620 (M), a potent ATR inhibitor, has synergistic activity with cisplatin (C) in multiple preclinical models, resulting in DNA damage and antitumor activity. We hypothesize that inhibition of both homologous recombination and base excision repair through the combination of M6620 and veliparib (V, a potent inhibitor of PARP1/2) would result in accumulation of lethal double stranded breaks induced by cisplatin and increased antitumor activity and initiated a phase-1 dose escalation trial of this combination in patients (pts) with advanced solid tumors (NCT02723864). Methods: This is a standard 3+3 dose escalation design with 21-day cycles. M is given IV day 2 (D2) and D9; V orally twice daily D1-3 and D8-10; C IV D1 (and D8 from dose level 3 [DL3] onwards) at 40 mg/m 2 (with option of holding after cycle 6). Primary objectives: safety; tolerability; maximum tolerated dose (MTD). Secondary objectives: pharmacodynamic (PD) biomarkers; antitumor activity. Dose-limiting toxicity (DLT) evaluated during cycle 1, response using RECIST 1.1. Results: Thirty-seven patients enrolled, median 5 lines of prior therapy (Range 1-12). MTD: V 200 mg, M 210 mg/m 2 , C 40 mg/m 2 (DL6). DLT: grade (gr) 4 thrombocytopenia (DL4), hypophosphatemia (not resolved in 24 hrs., DL3), infusion reaction (DL7). Common gr 3/4 toxicities: anemia (41%), thrombocytopenia (30%), neutropenia (27%), hyponatremia (11%) and hypophosphatemia (8%). Of 34 pts evaluable for response: 2 partial response (PR) (6%, 1 confirmed & 1 transient), 22 stable disease (SD) (65%, median 4 cycles, range 2-11). Of 24 pts with PR/SD, 22 had prior platinum chemotherapy. After July 2018, V was held for gr ≥2 anemia until improved to gr 1, followed by dose reduction. Of 5 pts treated in this period, 3 required V held. PD analysis of circulating tumor cells is underway to elucidate biomarkers of DNA damage and apoptosis. Conclusions: This combination of M6620, veliparib and cisplatin is safe, with activity seen in pts having received prior platinum. The most common toxicity was anemia, which prevented adequate delivery of veliparib. While MTD was established in a heavily pretreated population, consideration should be given to continued dose escalation in pts who have received fewer prior lines of therapy. Funded in part by NCI Contract No. HHSN261200800001E. Clinical trial information: NCT02723864.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.3067
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 3
    Online Resource
    Online Resource
    Interleukin-6 (IL-6) as an inflammatory biomarker in patients with hepatobiliary cancers.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 3_suppl ( 2015-01-20), p. 257-257
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 3_suppl ( 2015-01-20), p. 257-257
    Abstract: 257 Background: IL-6 is an inflammatory cytokine that modulates growth and differentiation of tumor cells. The role of IL-6 as a biomarker in this cancer subset population remains questionable. We aimed to study IL-6 levels in patients with hepatobiliary cancer and the associated patient characteristics. Methods: Stored serum from 91 patients with treatment-naïve hepatobiliary cancers (hepatocellular carcinoma, gallbladder cancer, intra- and extra-hepatic cholangiocarcinoma) were measured for IL-6 levels. Demographics and clinical parameters were collected from retrospective chart review. IL-6 was measured in stored serum from 91 controls, matched for age, gender and BMI. Associations between baseline covariates and IL6 measurements and differences in Overall Survival (OS) were assessed using Accelerated Failure Time (AFT) models. P-values 〈 0.05 were considered statistically significant. All data analyses were generated using SAS/STAT software, Version 9.4. Results: A total of 91 cases+91 controls were analyzed: 68% males in each set. IL-6 levels were significantly higher in the cases than the controls [median: 15.2pg/ml vs 1.7pg/ml p 〈 0.01]. Amongst cancer patients the following elements were associated with significantly higher levels of IL-6: cirrhosis (AF=3.18 p 〈 0.01), uncontrolled pain (AF=1.97 p 〈 0.01), worse ECOG status (p 〈 0.01) and portal vein thrombosis (AF=1.57, p=0.03). A 3-fold increase in Alpha fetoprotein (AFP) corresponded with a 9% increase in IL-6 (AF=1.09, p=0.015). IL-6 appeared to be modestly higher in males [median: 4.47 vs 5.32 p=0.5]. IL-6 remained an independent predictor of OS after controlling for several possible confounders (AFP, Cirrhosis, portal vein thrombosis). Each 10-unit increase in IL-6 resulted in an 8% reduction in the time to death (AF=0.92 (95% CI:0.78 to 1.00) p=0.033). Conclusions: IL-6 levels are significantly elevated in hepatobiliary cancers, directly correlating with AFP. Higher IL-6 levels are associated with aggressive tumors and poorer survival. These findings suggests the potential prognostic/predictive value of IL-6 and should initiate early palliative care referrals. Anti-IL6 therapy could increase meaningful survival time for patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.3_suppl.257
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39)
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 17 ( 2021-06-10), p. 1842-1855
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 17 ( 2021-06-10), p. 1842-1855
    Abstract: To evaluate the addition of the humanized monoclonal antiprogrammed death ligand-1 (PD-L1) antibody, atezolizumab, to platinum-based chemotherapy and bevacizumab in newly diagnosed stage III or IV ovarian cancer (OC). METHODS This multicenter placebo-controlled double-blind randomized phase III trial (ClinicalTrials.gov identifier: NCT03038100 ) enrolled patients with newly diagnosed untreated International Federation of Gynecology and Obstetrics (FIGO) stage III or IV OC who either had undergone primary cytoreductive surgery with macroscopic residual disease or were planned to receive neoadjuvant chemotherapy and interval surgery. Patients were stratified by FIGO stage, Eastern Cooperative Oncology Group performance status, tumor immune cell PD-L1 staining, and treatment strategy and randomly assigned 1:1 to receive 3-weekly cycles of atezolizumab 1,200 mg or placebo (day 1, cycles 1-22), with paclitaxel plus carboplatin (day 1, cycles 1-6) plus bevacizumab 15 mg/kg (day 1, cycles 2-22), omitting perioperative bevacizumab in neoadjuvant patients. The co-primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat and PD-L1–positive populations. RESULTS Between March 8, 2017, and March 26, 2019, 1,301 patients were enrolled. The median progression-free survival was 19.5 versus 18.4 months with atezolizumab versus placebo, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.07; stratified log-rank P = .28), in the intention-to-treat population and 20.8 versus 18.5 months, respectively (hazard ratio, 0.80; 95% CI, 0.65 to 0.99; P = .038), in the PD-L1–positive population. The interim (immature) overall survival results showed no significant benefit from atezolizumab. The most common grade 3 or 4 adverse events were neutropenia (21% with atezolizumab v 21% with placebo), hypertension (18% v 20%, respectively), and anemia (12% v 12%). CONCLUSION Current evidence does not support the use of immune checkpoint inhibitors in newly diagnosed OC. Insight from this trial should inform further evaluation of immunotherapy in OC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.21.00306
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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