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)  (16)
  • Medicine  (16)
Material
Publisher
  • American Society of Clinical Oncology (ASCO)  (16)
Person/Organisation
Language
Years
Subjects(RVK)
  • Medicine  (16)
RVK
  • 1
    Online Resource
    Online Resource
    Postoperative adjuvant dose-dense chemotherapy with bevacizumab and maintenance bevacizumab after neoadjuvant chemotherapy for advanced ovarian cancer: A phase II AGOG/TGOG trial.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 5540-5540
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 5540-5540
    Abstract: 5540 Background: The objective of this study is to evaluate the safety and efficacy of adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after neoadjuvant chemotherapy (NAC) and interval debulking surgery (IDS) for stage III/IV ovarian, tubal, and primary peritoneal cancer. Methods: This phase II clinical trial using Simon's minimax two-stage design was conducted. At the first stage, 13 subjects were enrolled, and the trial would proceed to second stage if ≤3 subjects discontinued treatment for study-defined significant adverse events (AEs). Patients with stage III/IV ovarian, tubal, and primary peritoneal cancer deemed not feasible for primary cytoreductive surgery were enrolled after 3 to 4 cycles of NAC and IDS without disease progression. NAC could be either weekly paclitaxel (80mg/m 2 ) (dose-dense) plus 3-weekly carboplatin (AUC5-6) or 3-weekly conventional schedule. After IDS, postoperative dose-dense adjuvant chemotherapy for 3 cycles at least (best to 6 cycles), and 3-weekly bevacizumab 15mg/kg was given since postoperative cycle 2. Further 3-weekly maintenance bevacizumab 15mg/kg was given intravenously for 17 cycles. Results: Of the 22 enrolled subjects, 13 (59.1%) had no gross lesion after IDS. Of the 13 subjects enrolled on the 1st stage, one study-defined significant AE occurred, therefore the trial proceeded to the 2nd stage (n = 9). The median progression-free survival (PFS) was 22.1 months (95% confidence interval [CI], 13.7 – 30.5), and the median overall survival (OS) was 49.2 months (95% CI, 33.8 – 64.6). Peritoneal Cancer Index score at entering abdomen during IDS was significant for PFS ( 〉 12 vs ≤ 12: p = 0.003). One of the 22 subjects did not receive any study treatment. In the safety analysis (n = 21), grade 3/4 AEs included thrombocytopenia of 38.1%, neutropenia 71.4%, and anemia 28.6%. Study-defined significant AEs of bowel perforation, poor-healing wound, and hypertension were found in 1 case each, respectively. Conclusions: This phase II trial demonstrated adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after NAC was feasible with tolerable toxicity and comparable PFS/OS as compared to other studies using bevacizumab in the NAC phase or dose-dense scheduling throughout. Clinical trial information: NCT02022917.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.5540
    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
    PEP503 (NBTXR3), a radioenhancer, in combination with concurrent chemoradiation (CCRT) in locally advanced or recurrent head and neck squamous cell carcinoma (HNSCC): Dose-finding of a phase 1b/2 trial.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e18041-e18041
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e18041-e18041
    Abstract: e18041 Background: PEP503 (aka NBTXR3), a novel radioenhancer composed of functionalized hafnium oxide nanoparticles, is designed for intratumoral injection to increase radiation energy deposition within solid tumors and subsequent tumor cell killing, without increasing toxicity to surrounding healthy tissue. PEP503 nanoparticles plus RT has been tested in elderly HNSCC patients and has demonstrated a good safety profile. The phase 1b part of the study aimed to test the feasibility and the recommended phase 2 dose (RP2D) of PEP503 intratumoral injection when added with low-dose (LD) weekly cisplatin-containing chemoradiation (CCRT) in HNSCC. Methods: Patients who had T3-4 locally advanced HNSCC suitable for CCRT were eligible. An intratumoral single injection of PEP503 was performed 24 to 72 hours before the start of CCRT: consisting of IMRT (70̃72 Gy, 2-2.12 Gy/fraction) and weekly cisplatin (low dose, 40 mg/m 2 ) concurrently during IMRT. Traditional 3+3 design was planned for dose escalation and 5 levels of PEP503 were planned, including 5%, 10%, 15%, 22%, and 33% of the baseline GTV by MRI. PEP503 Intra-tumor dispersion was anayzed by CT-scan. Results: Twelve (12) patients (male/female: 11/1; oral cavity/oropharynx: 11/1) were enrolled, with 3, 6, and 3 patients at 5%, 10%, and 15% PEP503 dose levels, respectively, in combination with LD cisplatin CCRT. DLTs were observed in one patient at 10% dose level which were G3 ALT and G3 AST increased. Common G3 AEs observed across dose levels were stomatitis (50.0%), WBC decreased (33.3%), decreased appetite (16.7%), neutrophil count decreased (16.7%), and leukopenia (16.7%), and only one G4 AE (hyponatraemia) was observed. CT images demonstrated PEP503 within the tumor contour after injection throughout the CCRT period. Hafnium, for all patients, was either not detected or below the Lower Limit of Quantification (LLOQ) in the circulation 60 minutes after PEP503 intratumoral injection, and not found in urine. DCR was achieved in 100% of patients with responding patients for an ORR of 58.3%. No subjects received salvage surgery after study treatment. Study was terminated early before MTD and RP2D could be determined. Conclusions: Adding PEP503, a radioenhancer, via a single intratumoral injection to weekly cisplatin-containing CCRT was feasible and safe for patients with locally advanced or recurrent LA-HNSCC. RP2D was not reached due to study early termination. Clinical trial information: NCT02901483.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e18041
    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
    Genome-wide association analysis in host genetic characteristics of progression to high-grade cervical intraepithelial neoplasia or higher for women with human papillomavirus infection and normal cytology.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 6033-6033
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 6033-6033
    Abstract: 6033 Background: Human papillomavirus (HPV) testing is widely used for cervical cancer screening. The hazard ratio of developing cervical intraepithelial neoplasia grade 2 or higher (CIN2+) in HPV-positive/ normal cytology women is 20–34 fold as compared to those with HPV-negative/normal cytology. HPV-positivity would cause substantial anxiety. Apart from viral factors such as high-risk (hr) types, it is important to identify host characteristics for predicting outcome. Methods: An initial genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) by Affymetrix Axiom™ Genome-Wide Human Arrays was conducted on 505 cases with histological diagnosis of CIN2+ (group D1) versus 920 female controls. An additional set of 2315 female controls from the Taiwan Biobank genotype array were added in the discovery stage. The identified 29 CIN2+ -associated SNPs from GWAS (p 〈 5 x 10 −6 ) were verified in an independent cohort (group D2 [n = 306] versus group N [n = 600] ). Group N were HPV-negative/normal cytology women from a population-based cervical cytology and HPV co-test study. A cohort with HPV-positive/normal cytology (group P, n = 755) underwent follow-up and was served as the prediction set. The predictive validity was analyzed by logistic regression and receiver operating characteristic (ROC) curve analysis. Results: Thirty-three individuals of the group P progressed to CIN2+ (median follow-up: 23.7 months, range 4.0–122.1). A risk-predictive panel of 8 SNPs rs3097662, rs35979982, rs7763822, rs4282438, rs3128927, rs7759943, rs213194, rs17835649 which were significant in the replication (p 〈 0.05) was used to train models for disease risk prediction using the combination of GWAS and verification sets. Two prediction models were finalized and determined using 7 SNPs for hr- and low-risk (lr) HPV groups respectively (sensitivity 0.72 and 0.75, specificity 0.651 and 0.884, area under the ROC curve 0.703 and 0.701). Among group P with hr-HPV, those carried 〈 6 risk-alleles had significantly decreased hazard (log-rank p 〈 0·001) of progression to CIN2+ than those with ≧6 risk-alleles, while among group P with lr-HPV, those with predictive probability of ≥ 0·095 had a cumulative risk of progression of 10% at 3 years. Conclusions: Two risk-predictive SNP panels including 7 SNPs with hr- or lr-HPV groups can assist risk stratification among HPV-positive/ normal cytology women. These panels could be further tested in other ethnic populations.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.6033
    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
  • 4
    Online Resource
    Online Resource
    GALNT14 genotype-guided, sorafenib in combination with transarterial chemoembolization in hepatocellular carcinoma: An interim report of a prospective randomized controlled trial.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e15657-e15657
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e15657-e15657
    Abstract: e15657 Background: Sorafenib is the only approved targeted agent for treatment of unresectable hepatocellular carcinoma (HCC). Transarterial chemoembolization (TACE) is the mainstay of treatment for advanced HCC patients in Barcelona Clinical Liver Cancer (BCLC) stage B. Previous randomized controlled trials did not show definite beneficial effect for TACE + sorafenib combination therapy in Asian HCC patients. Recently, an SNP marker on GALNT14gene, rs9679162, was found associated with therapeutic outcomes in HCC patients receiving chemotherapy or chemoembolization, wherein rs9679162-TT genotype was associated with a favorable therapeutic response. In this study, we examined whether this marker could be used as a guide for TACE + sorafenib therapy. Methods: From 2015-Aug, HCC patients in BCLC stage B were genotyped for GALNT14-rs9679162. Patients with genotype TT were treated with TACE alone. Patients with non-TT (CT or CC) were randomized 1:1 to receive TACE + sorafenib treatment or TACE treatment alone (NCT02504983). Results: Interim analysis was performed on 2017-Jan. Totally 40 patients were enrolled. Of them, 16 and 24 patients had GALNT14-TT and non-TT genotypes, respectively. Of the non-TT patients, 11 and 13 patients were randomized into TACE alone (TACEA) and TACE + sorafenib (TACE+S) group. TACEA patients had significant shorter time-to-tumor progression compared with TACE+S (P = 0.019) and GALNT14-TT patients (P 〈 0.001). No significant difference was found for time-to-therapeutic response (CR + PR) between the three groups. However, when evaluating the time-to-therapeutic response occurring 〉 3 m of the first TACE (excluding early response), it was found that TACEA patients had significant longer time-to-therapeutic response compared with TACE+S (P = 0.046) and GALNT14-TT patients (P = 0.034). Conclusions: The interim analysis confirmed that patients with GALNT14-TT genotype had a favorable TACE response compared with the non-TT genotype. In addition, in patients with non-TT genotype, TACE + sorafenib combination therapy had a significantly better therapeutic response compared with TACE alone. Clinical trial information: NCT02504983.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.e15657
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Induction bevacizumab, etoposide and cisplatin followed by whole brain radiotherapy (WBRT) versus WBRT alone in breast cancer with untreated brain metastases: Results of a randomized phase II A-PLUS trial.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 1082-1082
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 1082-1082
    Abstract: 1082 Background: Our previous study ( Clin Cancer Res. 2015;21(8):1851) demonstrated that bevacizumab preconditioning followed by etoposide and cisplatin (BEEP) is a highly effective treatment for breast cancer (BC) patients (pts) with brain metastases (BM) progressing from WBRT. We conducted a randomized phase II study A-PLUS (NCT02185352) to test whether using BEEP as an induction therapy could enhance the efficacy of WBRT and provide systemic control. Methods: BC pts with measurable BM not suitable for surgery/radiosurgery and had not received WBRT were randomized (2:1) to experimental arm: induction BEEP for 3 cycles (~2 months [ms]) followed by WBRT or control arm: upfront WBRT. The BEEP regimen consists of bevacizuma b 15 mg/kg on day 1, and etoposide 70 mg/m 2 /day on days 2-4, cisplatin 70 mg/m 2 on day 2, followed by prophylaxis GCSF, every 21 days. After WBRT in both arms, pts received treatment of physician’s choice except BEEP until BM progression. Stratification was based on the Graded Prognostic Assessment score. Primary endpoint was brain-specific progression free survival (BS-PFS) based on RECIST 1.1, with a total of 108 pts, power of 0.8 at the 2-sided α level of 0.2. Results: Of 112 enrolled pts, 74 were in experimental arm and 38 in control arm. Baseline patient characteristics were generally balanced between arms. With median follow up of 28.7 ms, median BS-PFS was 8.1 vs. 6.5 ms ( p= 0.146; HR 0.71 [95% CI 0.44-1.13]), which met the primary endpoint (pre-defined α level of 0.2). Results of preplanned analysis included: 2-month brain-specific objective response rate of BEEP alone vs. WBRT was 41.9% vs. 52.6% ( p= 0.613); 8-month BS-PFS rate was 48.7% vs. 26.3% ( p= 0.027); median PFS was 6.4 vs. 4.7 ms ( p= 0.071; HR 0.67 [95% CI 0.43-1.04] ), and extra-BM PFS was 7.9 vs. 5.0 ms ( p= 0.141; HR 0.71 [95% CI 0.46-1.12]). Median overall survival was 15.6 vs. 13.6 ms ( p= 0.855; HR 0.96 [95% CI 0.59-1.55] ), with 31.6% of pts in control arm received BEEP regimen treatment after BM progression. The most common all-grade adverse events (AEs) in experimental arm were neutropenia (30.2%), nausea (27.9%), anemia (27.4%), and leukopenia (24.2%). Most AEs were mild to moderate in severity. Two pts discontinued BEEP treatment due to grade 4 nephrotoxicity and grade 3 infection, respectively. Conclusions: BEEP as induction treatment followed by WBRT for BC pts with BM may improve control of both BM and systemic disease. Further validation by a phase III study is necessary. Clinical trial information: NCT02185352 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.1082
    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
  • 6
    Online Resource
    Online Resource
    The association of progesterone receptor and abnormal p53 expression in endometrioid endometrial cancer.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e17611-e17611
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e17611-e17611
    Abstract: e17611 Background: Based on the TCGA endometrial cancer study results, a clinically applicable classification that identifies distinct subgroups with prognostic signature, the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), has been built and validated. It shows that those with abnormal expression of p53 (p53abn) are the group with the worst prognosis. We attempted to explore the association of p53abn and progesterone receptor (PR) in endometrioid endometrial cancer. Methods: We included 397 consecutive endometrial cancer cases of endometrioid histology with adequate tumor tissue in the formalin-fixed, paraffin-embedded (FFPE) block and available follow-up information. This study was granted by Chang Gung Medical Foundation IRB 201702242B0D001. Sanger sequencing to assess the POLE exonuclease domain hotspot mutations of exon 9-14 and immunohistochemical staining on FFPE tumor tissue sections for p53, ER, PR, and mismatch repair proteins were performed. Immunohistochemical p53 expression of cancer cell nucleus was recorded as completely negative (0%), weakly positive (1-59%), and diffusely strong positive ( 〉 60%). Tumors with weak positive p53 staining were defined as p53 wild type (p53wt), while the other two were defined as p53 abnormal (p53abn). PR scores were calculated by multiplying the average staining intensity by the tumor cell nucleus stained percentage. We arbitrarily defined a progesterone receptor score of 100 or higher as positive (PR+). Progression-free and endometrial cancer-specific overall survivals starting at the date of diagnosis were evaluated using Kaplan-Meier method and compared by log-rank test between groups. Results: PR was positive in 82% of all studied cases. Of the 48 cases with p53abn tumor, 35(73%) were PR (+). With a median follow-up of 74 months, the progression-free survival and cancer-specific survival of patients with PR+ tumors (N = 310) were 93% and 96.8%, respectively, compared with 75% and 85.7% of those with PR- tumors (N = 70) (both p 〈 0.001, log-rank test). Among those with P53abn, PR expression was associated with a favorable progression-free survival ( p = 0.081) and better cancer-specific survival ( p = 0.044). POLEmut, POLE mutated; dMMR, deficient mismatch repair PR+, progesterone receptor score ≥100, ER+, estrogen receptor score ≥100; p53abn, abnormal p53 expression. MMR was undetermined in 32 cases, PR in 17 cases, ER in 17 cases, and p53 was undetermined in 10 cases. POLE status was detected in all cases. Cases with POLE wild type, proficient mismatch repair, progesterone score 〈 100, estrogen score 〈 100 and wild type p53 were not listed in this table. Conclusions: Our study showed that incorporating PR into prognostic molecular markers for endometrioid endometrial cancer might provide further risk stratification. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e17611
    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
  • 7
    Online Resource
    Online Resource
    Oral paclitaxel in the treatment of metastatic breast cancer (MBC) patients.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 1084-1084
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 1084-1084
    Abstract: 1084 Background: Intravenous (IV) paclitaxel is an effective treatment for breast cancer. Oral administration paclitaxel is preferable to IV regarding minimizing IV injections, anaphylactic reactions to cremaphor, steroid pre-medications, hospital visits, and relevant costs. However, paclitaxel has poor oral absorption due to active excretion by P-glycoprotein (P-gp) in the intestinal cells. Oraxol (Athenex, USA) is an oral paclitaxel and HM30181, a novel oral inhibitor of intestinal P-gp which enables the oral administration of paclitaxel. We report the final results of a pharmacokinetics (PK) study, including clinical response and tolerability of Oraxol in treatment of metastatic breast cancer patients. Methods: Multicenter, single-arm, open-label, PK study of Oraxol (HM30181A at 15mg, plus oral paclitaxel 205mg/m 2 ) administered orally for 3 consecutive days weekly for up to 16 weeks. Paclitaxel PK was assessed at week-1 and week-4. Tumor Response was measured at weeks 8 and 16 using RECIST criteria 1.1. Toxicity was assessed using CTCAE v4.03. Results: Twenty-eight MBC patient were studied with a mean age of 56.6 years (range: 38 - 79 yrs). 26 patients had failed mutiple previous chemotherapies. There were 11 (42.3%) partial response, 12 (46.2%) stable disease and 3 (11.5%) progressive disease in 26 evaluable patients. Three patients had treatment-related SAEs (grade ≥3 neutropenia) and all patients recovered completely. PK results showed that the AUC of oral paclitaxel at week-1 was reproducible at week-4 (3050 to 3594 ng-hr/mL). Conclusions: Oral paclitaxel showed very encouraging anti-cancer activity in MBC patients who failed previous chemotherapies with acceptable toxicity. Weekly oral paclitaxel can achieve paclitaxel exposure similar to that of weekly IV paclitaxel (80mg/m 2 ) reported previously. PK of oral paclitaxel is reproducible. Clinical trial information: NCT03165955.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.1084
    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
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Different efficacy of pembrolizumab in overall survival between Asians and non-Asians with advanced cancers: A systematic review and meta-regression analysis.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e13597-e13597
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e13597-e13597
    Abstract: e13597 Background: Immune checkpoint inhibitors have revolutionized the treatment landscape of malignancy. However, disproportionate enrollment among different races/ethnicities in global trials placed the generalizability in doubt. This meta-analysis aimed to estimate the relative efficacy of pembrolizumab between Asians and non-Asians with advanced cancers. Methods: A systematic review was conducted in PubMed, Cochrane Library, Embase, and Web of Science. The meta-analysis included phase 3 randomized controlled trials investigating pembrolizumab in advanced cancers with available subgroup analysis for Asians and non-Asians. The experimental strategies involved monotherapy versus standard-of-care (SOC) or best supportive care, an add-on to SOC, and combined with multikinase inhibitor versus standard chemotherapy, regardless of the setting. The primary and secondary effect measures were the mean difference (MD) in the natural logarithm (i.e., log) of the hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) between the two subgroups [MD=log(HR Asians )−log(HR Non-Asians )=log(HR Asians /HR Non-Asians )]. We used the random-effects meta-analysis to calculate the pooled ratio of HRs (i.e., exp(MD)) and implemented a meta-regression analysis to identify significant covariates. The heterogeneity among the selected studies was evaluated using the Chi-squared Q test and the I 2 statistic. Results: A total of 17 and 11 trials were selected in the meta-analysis for OS and PFS, respectively. These trials reported available subgroup results on Asians and non-Asians (patient numbers 2,732 [25.49%] and 7,000 [65.32%] for OS; 1,438 [22.50%] and 4,129 [64.61%] for PFS). The pooled ratio of HRs for OS was 0.87 (95% confidence interval [CI], 0.76−0.99; p = 0.0391; Chi-squared Q test Χ 2 = 20.84, p = 0.29; I 2 = 23.9%), favoring Asians, and no significant difference was found in PFS (the pooled ratio of HRs 0.93; 95% CI, 0.82−1.07; p = 0.2391; Chi-squared Q test Χ 2 = 7.37, p = 0.77; I 2 ≈ 0%). Both linear meta-regression analyses revealed an open-label design as an important covariate accounting for the observed difference, favoring non-Asians (estimated ratios of HR, 1.6318 for OS [95% CI, 1.1442-2.3273]; 1.3429 for PFS [95% CI, 1.0007−1.8020] ). The sensitivity analysis showed that the percentage of subsequent treatment or post-progression programmed cell death 1 (PD-1)/ligand 1 (PD-L1) inhibitors had no significant impact. Conclusions: Asians receiving pembrolizumab for advanced cancers may have a superior OS advantage than non-Asians. Although the results warranted further exploration, this meta-analysis provided insight into clinical research design.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e13597
    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
  • 9
    Online Resource
    Online Resource
    ORACLE-RIPA study: A phase II, randomized, open-label, parallel-group study comparing the immune modulation effect of neoadjuvant ribociclib, palbociclib, and abemaciclib in early ER+/HER2- breast cancer.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS632-TPS632
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS632-TPS632
    Abstract: TPS632 Background: CDK4/6 inhibitors (CDK4/6i), ribociclib, palbociclib, and abemaciclib, provide similar progression-free survival (PFS) benefits when combined with endocrine therapy in ER+/HER2- metastatic breast cancer (MBC) patients. However, not all CDK4/6i have demonstrated overall-survival (OS) benefits in their respective phase III trials. Both, ribociclib and abemaciclib, have shown significant OS benefits in ER+/HER2- MBC patients, but palbociclib has not. Because of similar benefits of the 3 CDK4/6i on PFS, the OS benefit is likely not a result of differences in their synergistic efficacy of a CDK4/6i with endocrine therapy. CDK4 inhibition on cancer cells can also result in upregulation of MHC-I and MHC-II expression on cell surface and Rb-dependent interferon-gamma secretion. CDK6 inhibition might inhibit T cell and NK cell proliferation causing a negative effect on the tumor microenvironment. CDK6 inhibition can also reduce regulatory T cell numbers and increase cytokine production to enhance cytotoxic T cell function. Thus, we hypothesize that the differential impact of the 3 CDK4/6i on OS might be resulting from different immunomodulation effects. To investigate the functional alterations of the CDK4/6i on the BC microenvironment, the neoadjuvant treatment setting is best to compare the immune modulation effects of CDK4/6i from pre-treatment and post-treatment tumor tissues. Methods: This phase II multicenter, randomized, open-label, parallel-group study evaluates the immunomodulation effects of the 3 different CDK4/6i (ribociclib, palbociclib, or abemaciclib) combined with letrozole in neoadjuvant early ER+/HER2- breast cancer patients. A total of 20 patients will be enrolled into each treatment arm. The major inclusion criteria are female patients aged ≥ 20 years old, having a histologically and/or cytologically confirmed diagnosis of ER+ ( 〉 10%) and/or PR+, HER2 negative (IHC 0+/1+, or IHC 2+ plus FISH negative) breast cancer, stage II/III, and adequate organ function. The treatment will12 weeks of letrozole plus a CDK4/6i. Premenopausal patients will receive GnRH agonist. Breast tumor biopsy, blood and stool samples will be collected prospectively at the time prior to treatment initiation, at 2 weeks after treatment, and at surgery. A description summary will be utilized to compare the results between the 3 CDK4/6i. The trial results will address questions about differences or similarities of the 3 CDK4/6i within the same study. The study is currently enrolling at 3 medical centers s in Taiwan. Clinical trial information: Pending formal number assignment .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.TPS632
    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
  • 10
    Online Resource
    Online Resource
    Correspondence on Concerns About Methodology and Confounding
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 21 ( 2022-07-20), p. 2390-2390
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 21 ( 2022-07-20), p. 2390-2390
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.22.00237
    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
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...