GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Society of Clinical Oncology (ASCO)  (24)
  • 2020-2024  (24)
Material
Publisher
  • American Society of Clinical Oncology (ASCO)  (24)
Person/Organisation
Language
Years
  • 2020-2024  (24)
Year
Subjects(RVK)
  • 1
    Online Resource
    Online Resource
    Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell–Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 18 ( 2021-06-20), p. 1959-1970
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 18 ( 2021-06-20), p. 1959-1970
    Abstract: Glofitamab is a T-cell–engaging bispecific antibody possessing a novel 2:1 structure with bivalency for CD20 on B cells and monovalency for CD3 on T cells. This phase I study evaluated glofitamab in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). Data for single-agent glofitamab, with obinutuzumab pretreatment ( Gpt) to reduce toxicity, are presented. METHODS Seven days before the first dose of glofitamab (0.005-30 mg), all patients received 1,000 mg Gpt. Dose-escalation steps were determined using a Bayesian continuous reassessment method with overdose control. Primary end points were safety, pharmacokinetics, and the maximum tolerated dose of glofitamab. RESULTS Following initial single-patient cohorts, 171 patients were treated within conventional multipatient cohorts and received at least one dose of glofitamab. This trial included heavily pretreated patients with R/R B-NHL; most were refractory to prior therapy (155; 90.6%) and had received a median of three prior therapies. One hundred and twenty-seven patients (74.3%) had diffuse large B-cell lymphoma, transformed follicular lymphoma, or other aggressive histology, and the remainder had indolent lymphoma subtypes. Five (2.9%) patients withdrew from treatment because of adverse events. Cytokine release syndrome occurred in 86 of 171 (50.3%) patients (grade 3 or 4: 3.5%); two (1.2%) patients experienced grade 3, transient immune effector cell–associated neurotoxicity syndrome-like symptoms. The overall response rate was 53.8% (complete response [CR], 36.8%) among all doses and 65.7% (CR, 57.1%) in those dosed at the recommended phase II dose. Of 63 patients with CR, 53 (84.1%) have ongoing CR with a maximum of 27.4 months observation. CONCLUSION In patients with predominantly refractory, aggressive B-NHL, glofitamab showed favorable activity with frequent and durable CRs and a predictable and manageable safety profile.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.20.03175
    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
  • 2
    Online Resource
    Online Resource
    Integrated safety summary of single-agent mirvetuximab soravtansine in patients with folate receptor α (FRα)-positive recurrent ovarian cancer: Phase 1 and 3 clinical trials.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 5574-5574
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 5574-5574
    Abstract: 5574 Background: Available chemotherapies for platinum-resistant ovarian cancer (PROC) have limited clinical activity and considerable toxicity. Mirvetuximab soravtansine (MIRV) is a first-in-class antibody drug conjugate (ADC) comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin-targeting agent that has demonstrated significant anti-tumor activity in this difficult to treat population. The objective is to characterize the tolerability profile of MIRV in a pooled analysis of experience when administered as monotherapy in patients (pts) with FRα positive recurrent ovarian cancer. Methods: Retrospective pooled analysis included pts enrolled across three studies: phase 1 first-in-human, phase 3 FORWARD I, and phase 3 SORAYA. Analysis included pts with FRα positive recurrent ovarian cancer and those pts with low, medium, and high FRα expression by immunohistochemistry (Roche FOLR1 Assay ≥ 25% of cells with PS2+ staining intensity). All pts received intravenous MIRV at 6 mg/kg, adjusted ideal body weight, on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity. Results: 464 pts were included from 15 countries, with key characteristics: median age 63 yrs, 87% 1-3 prior therapies, 91% platinum free interval ≤6 months, 65% prior bevacizumab, and 25% prior PARPi. The most common treatment-related adverse events (TRAE) (all grade, grade 3+) included blurred vision (42%, 3%), nausea (40%, 2%), diarrhea (33%, 2%), fatigue (31%, 2%), keratopathy (26%, 3%), and dry eye (22%, 1%). TRAEs leading to a dose delay or reduction occurred in 33% and 21% of pts, respectively. Seven % discontinued due to a TRAE. Four pts ( 〈 1%) discontinued MIRV due to an ocular event. Ninety % of pts with a grade 2+ blurred vision resolved to grade 0 or 1, 93% of pts with grade 2+ keratopathy resolved to grade 0 or 1. No corneal ulcers or perforation have been reported and no patient with a serious ocular event has been reported to have permanent sequelae. Conclusions: In a pooled analysis of 464 patients, MIRV monotherapy has a differentiated and predictable safety profile consisting primarily of low grade and reversible gastrointestinal and ocular events. These events were managed with supportive care and dose modifications if needed, with a low rate of treatment-related discontinuation. The safety profile of MIRV in recurrent ovarian cancer along with the anti-tumor activity in PROC (32.4% ORR Matulonis SGO 2022) support a favorable benefit/risk in this population. Clinical trial information: NCT01609556, NCT04296890, NCT02631876.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.5574
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Favorable toxicity of chemoradiation for muscle-invasive bladder cancer in elderly, frail patients.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 6_suppl ( 2022-02-20), p. 507-507
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 507-507
    Abstract: 507 Background: Chemoradiation (CRT) for bladder cancer provides comparable outcomes to radical cystectomy; however, concerns regarding toxicity, particularly in elderly, frail patients limit its utilization. Methods: We identified 150 consecutive patients who underwent definitive CRT for T1-4N0M0 bladder cancer at Memorial Sloan Kettering Cancer Center between 2005 and 2020. Most were men (71.3%), elderly (median age, 77.5 years), had high Charlson Comorbidity Index (CCMI) score (median, 7), were nonsurgical candidates (65.3%), Stage T2 (75.3%) and had a macroscopically complete TURBT (65%). 24% of patients received neoadjuvant platinum-based chemotherapy. Concurrent gemcitabine was used in 98.7%. 116 (77.3%) patients underwent 45Gy to the pelvic lymphatics/whole bladder followed by bladder boost (median total dose, 66.6 Gy) and 34 patients (22.7%) received 55 Gy in 20 fractions to the whole bladder/ urethra only. Fiducial markers for image-guidance were used in 55% (83/150) of cases. Patients were followed post-treatment with toxicity assessment, cytology/cystoscopy and imaging every 3 months year 1, every 6 months for years 2-3 and annually thereafter. Acute (≤3 months) and late ( 〉 = 3 months) gastrointestinal (GI) and genitourinary (GU) toxicities were assessed according to CTCAE v4.0. Complete response (CR) was defined as no evidence of disease at 3-month follow up. Survival outcomes were estimated using the Kaplan-Meier method. Median follow up was 31 months (range, 0-155 months). Results: The majority (94%) completed the prescribed course of radiation. Acute grade 3 GU and GI toxicities occurred in 2% and 5.3% of patients, respectively. No acute grade 4 toxicity was recorded. The most common GU and GI toxicities were radiation cystitis and diarrhea. Late grade ≥2 GU and GI toxicity occurred in 11.2% and 0.7% or cases, respectively. One late grade 4 GI toxicity was recorded (small bowel obstruction 7 months after completion of CRT). 80% (n = 120) of patients achieved a CR. Of complete responders, 30% (36/120) developed recurrent disease at a median time of 13.8 months (range, 3.2- 90.4). Among them, local only vs regional/distant recurrence rates were 72.2% and 27.8%, respectively. Of entire cohort, 40% of patients were alive and 31% had died with no evidence of disease at last follow up. While the estimated 5-year OS was 48% (95% CI, 39%, 59%), the estimated 5-year disease-specific mortality rate was 31% (95% CI, 24%, 40%). On univariate analysis, younger age (p 〈 0.001), receipt of neoadjuvant chemotherapy (p = 0.006) and surgical candidacy (p = 0.041) were predictive of improved OS. On multivariate analysis, only younger age was significant (p = 0.006). Conclusions: CRT had a favorable toxicity profile and encouraging cancer control outcomes in this unselected, mostly elderly and frail patient cohort.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.6_suppl.507
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Association of prior immune checkpoint blockade (ICB) with longer progression-free survival (PFS) in patients treated with intermittent versus continuous dabrafenib and trametinib: A post-hoc analysis of S1320.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 10039-10039
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 10039-10039
    Abstract: 10039 Background: S1320 is a phase 2 randomized clinical trial presented at the 2020 AACR Annual Meeting in April demonstrating that continuous dosing of dabrafenib and trametinib yields longer PFS than intermittent dosing of these agents in patients with BRAF V600E/K melanoma. Here we look at the association between prior exposure to ICB and PFS in patients randomized to either intermittent or continuous dosing on S1320. Methods: Patients without disease progression after 8 weeks of dabrafenib and trametinib were randomized 1:1 to proceed with intermittent therapy (3-week-off, 5-week-on) or to stay on the continuous daily dosing schedule. The design called for 206 randomized patients with the primary outcome of PFS. Response assessments were made using RECIST v1.1 at 8-week intervals. A post-hoc analysis assessed differences in PFS in the pool of all randomized patients based on prior exposure to anti-PD1 antibodies, a randomization stratification factor. Kaplan-Meier estimates and multivariable Cox regression models (controlling for pre-randomization age, Zubrod performance status, LDH, unknown primary, M-Stage) were used to evaluate the association between this stratification factor and PFS. Results: Of 242 patients treated on study, 105 were randomized to continuous dosing, 101 to intermittent dosing, and 36 were not randomized due to disease progression at 8 weeks or other factors. 37% of the 242 enrolled and 37% of the 206 randomized patients had previously been treated with ICB. Among all randomized patients, there were no differences in baseline characteristics comparing patients with and without prior immune checkpoint inhibitor exposure: age median 62 vs 59, LDH elevation 37% vs 39%,, stage IVB/C 73% vs 64%, Zubrod performance status 0, 57% vs 58%. PFS was longer in patients with prior ICB exposure (hazard ratio = 0.60, 95% confidence interval 0.41,-0.98, median = 6 vs 9 months from randomization, 8 vs 11 months from starting treatment). There was no difference in the association between prior ICB exposure and PFS between arms (interaction p-value = 0.62). Conclusions: In patients without early progression on dabrafenib and trametinib, PFS was longer with prior to exposure to ICB . Although the groups had similar baseline characteristics and rates of randomization, these results could still be influenced by non-controlled factors influencing clinicians’ decisions to start a patient on immune versus targeted therapy. Clinical trial information: NCT02196181.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.10039
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    A phase I study of nanoparticle albumin-bound sirolimus (NAB-S) combined with pazopanib (PAZO) in patients with advanced soft tissue sarcoma (STS).
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 11521-11521
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 11521-11521
    Abstract: 11521 Background: NAB-S (ABI-009, nab-rapamycin) is approved for treatment of adults with unresectable or metastatic perivascular epithelioid cell tumors. Albumin binding improves sirolimus solubility and may target it to tumoral cells. mTOR inhibition may enhance PAZO activity directly and by overcoming resistance. We assess feasibility and safety of the combination. Methods: Eligible patients (≥18y) had: advanced, unresectable, non-adipocytic STS progressing after 1-5 prior therapies; adequate end-organ function; ECOG performance status 0-1; measurable target lesions (RECIST v1.1); and no prior mTOR or angiogenesis inhibitor treatment. The study was conducted according to a 3+3 design. Initial cohorts received 800 or 400 mg PAZO daily and 60, 45 or 30 mg/m 2 of NAB-S on days 1 and 8 on a 21-day cycle. Subsequently, NAB-S was administered only on day 1 based on preliminary analysis of adverse events (AEs) and pharmacokinetics (PK). Primary endpoint was determination of maximally tolerated dose (MTD). Dose-limiting toxicities (DLT) were grade 3-5 adverse events (AE) during the first cycle not due to PAZO. Secondary endpoints included AE characterization (CTCAE v5.0), descriptive evaluation of responses and their duration, and correlative/PK studies. Results: 19 patients were treated; initially, 13 received NAB-S on days 1 and 8. DLT included thrombocytopenia (TCP, n = 7), decreased WBC/neutrophils (n = 2), increased lipase (n = 1), and proteinuria (n = 1). Due to overlapping AEs or possible NAB-S/PAZO interaction, further cohorts received 400 mg PAZO daily and either 30 or 45 mg/m 2 NAB-S (n = 6). There were no DLTs in the 30 mg/m 2 cohort (n = 3). In the 45 mg/m 2 cohort, 2 out of 3 patients had TCP meeting DLT definition. Grade 3-4 AEs in more than 10% included: TCP (58%), neutropenia (11%), leukopenia (11%), lymphopenia (11%), and diarrhea (11%). Any grade AEs in 〉 50% included: TCP (74%), mucositis (63%), fatigue (58%), and acneiform rash (53%). There was no grade 5 AEs. Of 19 treated, 11 (58%) discontinued due to disease progression, 3 (16%) due to AE (TCP-2, transaminitis-1), and 1 (5%) due to death from disease. Four (21%) remain on study as of 2/2023. 18 were evaluable for best response: 3 partial responses (PR; leiomyosarcoma, solitary fibrous tumor, spindle cell sarcoma), 13 stable disease (SD), 2 progressive disease. Clinical Benefit Rates (CBR = PR+SD) at 3 and 6 months were 61% (11/18) and 50% (9/18). Among the leiomyosarcoma subset, CBR at 3 and 6 months were 70% (7/10) and 60% (6/10). Correlative and pharmacokinetic results will be presented. Conclusions: Thrombocytopenia was the most prominent DLT when studying the NAB-S/PAZO combination. 3 patients out of 19 discontinued therapy due to AEs; the remainder continued therapy after adjustment. MTD and RP2D is NAB-S 30 mg/m 2 day 1 and PAZO 400 mg days 1-21. Preliminary evidence of activity of the combination was observed. Clinical trial information: NCT03660930 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.11521
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Elective Cancer Surgery in COVID-19–Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 1 ( 2021-01-01), p. 66-78
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 1 ( 2021-01-01), p. 66-78
    Abstract: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.20.01933
    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
  • 7
    Online Resource
    Online Resource
    CA-125 KELIM as a Potential Complementary Tool for Predicting Veliparib Benefit: An Exploratory Analysis From the VELIA/GOG-3005 Study
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 1 ( 2023-01-01), p. 107-116
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 1 ( 2023-01-01), p. 107-116
    Abstract: In VELIA trial, veliparib combined with carboplatin-paclitaxel, followed by maintenance (veliparib-throughout) was associated with improved progression-free survival (PFS) compared with carboplatin-paclitaxel alone in patients with high-grade ovarian carcinomas. We explored the prognostic value of the modeled cancer antigen (CA)-125 elimination rate constant K (KELIM), which is known to be an indicator of the intrinsic tumor chemosensitivity (the faster the rate of CA-125 decline, the higher the KELIM and the higher the chemosensitivity), and its association with benefit from veliparib. PATIENTS AND METHODS Individual KELIM values were estimated from longitudinal CA-125 kinetics. Patients were categorized as having favorable (≥ median) or unfavorable ( 〈 median) KELIM. The prognostic value of KELIM for veliparib-related PFS benefit was explored in cohorts treated with primary or interval debulking surgery, according to the surgery completeness, the disease progression risk group, and the homologous recombination (HR) status ( BRCA mutation, HR deficiency [HRD], or HR proficiency [HRP] ). RESULTS The data from 854 of 1,140 enrolled patients were analyzed (primary debulking surgery, n = 700; interval debulking surgery, n = 154). Increasing KELIM values were associated with higher benefit from veliparib in HRD cancer, as were decreasing KELIM values in HRP cancer. The highest PFS benefit from veliparib was observed in patients with both favorable KELIM and BRCA mutation (hazard ratio, 0.28; 95% CI, 0.13 to 0.61) or BRCA wild-type HRD cancer (hazard ratio, 0.43; 95% CI, 0.26 to 0.70), consistent with the association between poly (adenosine diphosphate-ribose) polymerase inhibitor efficacy and platinum sensitivity. In contrast, seventy-four percent of patients with a BRCA mutation and unfavorable KELIM progressed within 18 months while on veliparib. The patients with HRP cancer and unfavorable KELIM might have benefited from the veliparib chemosensitizing effect. CONCLUSION In addition to HRD/ BRCA status, the tumor primary chemosensitivity observed during the first-line chemotherapy might be another complementary determinant of poly (adenosine diphosphate-ribose) polymerase inhibitor efficacy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.22.00430
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    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
  • 9
    Online Resource
    Online Resource
    A phase I/II study of ruxolitinib with frontline neoadjuvant and post-surgical therapy in patients with advanced epithelial ovarian, Fallopian tube, or primary peritoneal cancer.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 5501-5501
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 5501-5501
    Abstract: 5501 Background: The Interleukin-6/JAK/STAT3 axis, via an increase in cancer stem-like cell (CSC) survival, is a reported driver of chemotherapy resistance. We hypothesized that addition of the JAK1/2 inhibitor ruxolitinib to standard chemotherapy would be tolerable and, by targeting therapy-resistant cells, improve the progression-free survival (PFS) of ovarian/fallopian tube/primary peritoneal carcinoma (OV/FT/PPC) patients treated in the up-front setting. Methods: Patients with OV/FT/PPC dispositioned to neoadjuvant chemotherapy were eligible for NRG-GY007 (NCT #02713386). In phase I, treatment was with dose-dense paclitaxel (P) 70 or 80 mg/m2 days 1, 8, and 15; carboplatin (C) AUC 5 or 6 day 1; and ruxolitinib (R) 15mg PO BID, every 21 days. In the absence of tumor progression or an inability to tolerate surgery, interval tumor reductive surgery (TRS) was required after cycle 3. After TRS, 3 additional cycles were administered, followed by maintenance ruxolitinib until progression, unacceptable toxicity, or voluntary withdrawal. In phase II, patients were randomized to dose-dense PC (arm 1) or dose-dense PC plus ruxolitinib (arm 2) at the phase I-defined dose of 15mg PO BID. After 3 cycles, TRS was performed, followed by another 3 cycles of the randomized regimen, without maintenance ruxolitinib. The primary phase II endpoint was progression-free survival (PFS). Results: 17 patients were enrolled in phase I. The MTD was P at 70, C at 5, and R at 15, which was chosen as the phase II dose. 130 patients were enrolled in phase II with a median follow-up of 24 months. There were five Grade 5 events in phase II, 2 in arm 1 and 3 in arm 2, with all except one being unrelated to therapy; a G5 febrile neutropenia in arm 2 was considered possibly related. In arm 2 there was potential trend towards higher grade 3-4 anemia (64% v 27% control), grade 3-4 neutropenia (53% v 37%), thromboembolic events (12.6% v 2.4%), and febrile neutropenia (6% v 0%). The HR for PFS was 0.702 (90% 1-sided CI = 0-0.89, log-rank p = 0.059). The median PFS in arm 1 was 11.6 versus 14.6 in arm 2. The overall survival HR = 0.785 (90% CI = 0.44 to 1.39, p = 0.70). There were no differences between rates of total gross resection. Conclusions: Ruxolitinib 15mg PO BID was well-tolerated with acceptable toxicity in combination with dose-dense PC. The primary endpoint of prolongation of PFS was achieved in the experimental arm. Further study of this combination can be considered. This trial also demonstrates the feasibility of early-phase randomized studies with novel agents and biospecimen collection in front line neoadjuvant treatment of ovarian cancer. Clinical trial information: 02713386.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.5501
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Pathologic Lymph Node Regression After Neoadjuvant Chemotherapy Predicts Recurrence and Survival in Esophageal Adenocarcinoma: A Multicenter Study in the United Kingdom
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 28 ( 2023-10-01), p. 4522-4534
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 28 ( 2023-10-01), p. 4522-4534
    Abstract: Lymph node regression after neoadjuvant chemotherapy predicts survival in esophageal adenocarcinoma.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.23.00139
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...