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  • American Society of Clinical Oncology (ASCO)  (12)
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  • American Society of Clinical Oncology (ASCO)  (12)
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  • English  (12)
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  • 1
    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
    detail.hit.zdb_id: 604914-X
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  • 2
    Online Resource
    Online Resource
    Phase II Trial of Cetuximab in Combination With Fluorouracil, Leucovorin, and Oxaliplatin in the First-Line Treatment of Metastatic Colorectal Cancer
    American Society of Clinical Oncology (ASCO) ; 2007
    In:  Journal of Clinical Oncology Vol. 25, No. 33 ( 2007-11-20), p. 5225-5232
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 33 ( 2007-11-20), p. 5225-5232
    Abstract: This phase II study investigated the efficacy and safety of cetuximab combined with standard oxaliplatin-based chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin [FOLFOX-4]) in the first-line treatment of epidermal growth factor receptor–expressing metastatic colorectal cancer (mCRC). Patients and Methods The activity of cetuximab plus oxaliplatin was investigated in colon cancer cell lines and xenograft models. In the clinical study, patients with mCRC received on day 1 of a 14 day cycle, cetuximab (initial dose 400 mg/m 2 during week 1, then 250 mg/m 2 weekly) followed by FOLFOX-4 (oxaliplatin 85 mg/m 2 on day 1; leucovorin 200 mg/m 2 on days 1 and 2, followed by fluorouracil 400 mg/m 2 bolus then 600 mg/m 2 intravenous infusion during 22 hours on days 1 and 2). Results The preclinical studies confirmed the supra-additive activity of cetuximab to oxaliplatin. In the clinical study, 43 patients were included, with a median age of 65 years (range, 43 to 78 years). Response rates (RRs) were 79% (unconfirmed) and 72% (confirmed), with 95% disease control. Median progression-free survival (mPFS) and median duration of response were 12.3 and 10.8 months, respectively. Ten patients (23%) underwent resection with curative intent of previously unresectable metastases. After a median follow-up of 30.5 months, median overall survival (mOS) was 30.0 months. Cetuximab did not increase the characteristic toxicity of FOLFOX-4 and was generally well tolerated. Conclusion Cetuximab in combination with FOLFOX-4 is a highly active first-line treatment for mCRC, showing encouraging RR, mPFS, and mOS values. The treatment resulted in a high resectability rate, which could potentially result in an improved cure rate. This combination is under phase III development.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2007.13.2183
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2007
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 3
    Online Resource
    Online Resource
    Germline NQO1c.559C〉T as a biomarker of genetic susceptibility to immune checkpoint blockade resistance.
    American Society of Clinical Oncology (ASCO) ; 2024
    In:  Journal of Clinical Oncology Vol. 42, No. 16_suppl ( 2024-06-01), p. 8537-8537
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 42, No. 16_suppl ( 2024-06-01), p. 8537-8537
    Abstract: 8537 Background: Tobacco is the main risk factor for developing lung cancer. Yet, some heavy smokers do not develop cancer while others do at young ages. The study of cancer immunology has led to the surge of immune checkpoint blockade (ICB), which transformed the treatment landscape of cancer pts. NQO1 has been associated with extreme phenotypes of high risk for the development of tobacco-induced NSCLC and with poor survival outcomes for xerographs. Development of biomarkers for ICB has been mainly focused on tumor-related factors while genetic susceptibility of the host has been poorly explored to date and some evidence suggests that genetic dysregulation may enables immune escape. Methods: From June 2016 to January 2023, 326 NSCLC pts from two main University Hospitals of Malaga (Spain) receiving ICB were prospectively enrolled, blood samples were gathered. We selected a representative set of 60 consecutive pts for exome sequencing to characterize the germline contribution to resistance (progression within the first 6 months of treatment). PBMC DNA was extracted and prepared for exome sequencing. Raw sequencing data was processed and aligned to a reference genome using BWA. Base recalibration, germline variant calling and variant filtering was performed through GATK. Survival probabilities were estimated with the Kaplan-Meier method and compared using the log-rank test. We explored the lung cancer related genes among our results. Results: Median age at diagnosis of 64 (54-85). 76,6% were men. 44/60 (73,3%) were adenocarcinoma (ADC), PD-L1≥1% in 55% of patients, 22% shown PD-L≥50%. 78% had advanced disease at diagnosis. 65% received ICB in combination with chemotherapy. We found NQO1c.559C 〉 T in 46,6% of pts (28/60). The variation was not associated with survival outcomes in the multivariant analysis (p 〉 0.05) but with poor OS for non-ADC histology (19.7m vs 6m for mutated and WT, respectively; p 〈 0.01). In addition, we found 26 germline variants associated with OS and PFS, and 52 variants with response to ICB. The variants were missense or involved a stop gain/loss. Conclusions: Exome sequencing analysis of germline variants could be a suitable methodology to identify subrogated biomarkers of immune resistance in NSCLC patients. NQO1c.559C 〉 T might help to identify poor prognosis non-ADC pts in the ICB setting.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2024.42.16_suppl.8537
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2024
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 4
    Online Resource
    Online Resource
    Effect of ctDNA whole-exome sequencing in pancreatic adenocarcinoma on prognostic value, actionable alterations, and organ tropisms in metastatic disease.
    American Society of Clinical Oncology (ASCO) ; 2024
    In:  Journal of Clinical Oncology Vol. 42, No. 16_suppl ( 2024-06-01), p. 4149-4149
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 42, No. 16_suppl ( 2024-06-01), p. 4149-4149
    Abstract: 4149 Background: The dismal prognosis associated with pancreatic ductal adenocarcinoma (PDAC) needs a deeper understanding of progression mechanisms and personalized treatment. While the prognostic value of ctDNA has already been established, this study purposes to apply plasma whole-exome sequencing (WES) to identify molecular alterations beyond KRAS. This approach aims to predict survival, uncover progression mechanisms, and identify therapeutic targets. Methods: Eighty metastatic PDAC patients were prospectively recruited and divided into two consecutive cohorts: discovery (n=37) and validation (n=43). Tumor and plasma obtained at diagnosis were analyzed using WES. The variant allele frequency (VAF) of KRASmutations was quantified by ddPCR in plasma at baseline and at response from all patients (n=80). Results: Plasma WES identified at least one pathogenic variant across all individuals, which can be categorized into four pathways: oncogenic mechanisms, DNA repair, microsatellite instability and TGFb pathway alterations. 7 unique druggable mutations were detected in tissue and 11 in plasma. Other targetable mutations ( CDK12, NF1, BRCA2, and TSC2), were prevalent in plasma but absent in tissue. Patients with survival less than 11 months showed enrichment in cellular organization pathways and exclusive targetable CDK12 mutations. Longer survival cases exhibited exclusive mutations in DNA regulation and repair genes. Patients with liver metastasis displayed unique mutations not just in KRAS but also in the adaptive immune response pathway genes. Baseline plasma KRAS mutations detected by ddPCR was associated with worse progression-free survival. (HR=2.315, CI 95%= 1.027-5.217, p = 0.038; and HR= 3.022, CI 95% = 1.299 - 7.030, p= 0.007 in the discovery and validation cohort, respectively). A significant risk of progression (p = 0.006) was observed if KRAS VAF at response assessment did not decrease, at least, 84.75% in both cohorts. Conclusions: ctDNA WES unveils molecular signatures of rapid progression, potential actionable alterations, and liver metastasis-specific mutations in the adaptive immune response pathway. KRAS detection at baseline and its evolution during treatment emerge as prognostic biomarkers. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2024.42.16_suppl.4149
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2024
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 5
    Online Resource
    Online Resource
    Clinical Presentation and Outcomes of Patients With Cancer-Associated Isolated Distal Deep Vein Thrombosis
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO)
    Abstract: Patients with isolated distal deep vein thrombosis (DVT) have lower rates of adverse outcomes (death, venous thromboembolism [VTE] recurrence or major bleeding) than those with proximal DVT. It is uncertain if such findings are also observed in patients with cancer. METHODS Using data from the international Registro Informatizado de la Enfermedad TromboEmbolica venosa registry, we compared the risks of adverse outcomes at 90 days (adjusted odds ratio [aOR]; 95% CI) and 1 year (adjusted hazard ratio [aHR; 95% CI] ) in 886 patients with cancer-associated distal DVT versus 5,196 patients with cancer-associated proximal DVT and 5,974 patients with non–cancer-associated distal DVT. RESULTS More than 90% of patients in each group were treated with anticoagulants for at least 90 days. At 90 days, the adjusted risks of death, VTE recurrence, or major bleeding were lower in patients with non–cancer-associated distal DVT than in patients with cancer-associated distal DVT (reference): aOR = 0.16 (0.11-0.22), aOR = 0.34 (0.22-0.54), and aOR = 0.47 (0.27-0.80), respectively. The results were similar at 1-year follow-up: aHR = 0.12 (0.09-0.15), aHR = 0.39 (0.28-0.55), and aHR = 0.51 (0.32-0.82), respectively. Risks of death, VTE recurrence, and major bleeding were not statistically different between patients with cancer-associated proximal versus distal DVT, both at 90 days: aOR = 1.11 (0.91-1.36), aOR = 1.10 (0.76-1.62), and aOR = 1.18 (0.76-1.83), respectively, and 1 year: aHR = 1.01 (0.89-1.15), aHR = 1.02 (0.76-1.35), and aHR = 1.10 (0.76-1.61), respectively. However, more patients with cancer-associated proximal DVT, compared with cancer-associated distal DVT, developed fatal pulmonary embolism (PE) during follow-up: The risk difference was 0.40% (95% CI, 0.23 to 0.58). CONCLUSION Cancer-associated distal DVT has serious and relatively comparable outcomes compared with cancer-associated proximal DVT. The lower risk of fatal PE from cancer-associated distal DVT needs further investigation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.23.00429
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 6
    Online Resource
    Online Resource
    Predictors of Survival After Head and Neck Squamous Cell Carcinoma in South America: The InterCHANGE Study
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  JCO Global Oncology , No. 6 ( 2020-11), p. 486-499
    Details
    In: JCO Global Oncology, American Society of Clinical Oncology (ASCO), , No. 6 ( 2020-11), p. 486-499
    Abstract: Head and neck squamous cell carcinoma (HNSCC) incidence is high in South America, where recent data on survival are sparse. We investigated the main predictors of HNSCC survival in Brazil, Argentina, Uruguay, and Colombia. METHODS Sociodemographic and lifestyle information was obtained from standardized interviews, and clinicopathologic data were extracted from medical records and pathologic reports. The Kaplan-Meier method and Cox regression were used for statistical analyses. RESULTS Of 1,463 patients, 378 had a larynx cancer (LC), 78 hypopharynx cancer (HC), 599 oral cavity cancer (OC), and 408 oropharynx cancer (OPC). Most patients (55.5%) were diagnosed with stage IV disease, ranging from 47.6% for LC to 70.8% for OPC. Three-year survival rates were 56.0% for LC, 54.7% for OC, 48.0% for OPC, and 37.8% for HC. In multivariable models, patients with stage IV disease had approximately 7.6 (LC/HC), 11.7 (OC), and 3.5 (OPC) times higher mortality than patients with stage I disease. Current and former drinkers with LC or HC had approximately 2 times higher mortality than never-drinkers. In addition, older age at diagnosis was independently associated with worse survival for all sites. In a subset analysis of 198 patients with OPC with available human papillomavirus (HPV) type 16 data, those with HPV-unrelated OPC had a significantly worse 3-year survival compared with those with HPV-related OPC (44.6% v 75.6%, respectively), corresponding to a 3.4 times higher mortality. CONCLUSION Late stage at diagnosis was the strongest predictor of lower HNSCC survival. Early cancer detection and reduction of harmful alcohol use are fundamental to decrease the high burden of HNSCC in South America.
    Type of Medium: Online Resource
    ISSN: 2687-8941
    URL: Article
    DOI: 10.1200/GO.20.00014
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 3018917-2
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  • 7
    Online Resource
    Online Resource
    Fludarabine, Cytarabine, Granulocyte Colony-Stimulating Factor, and Idarubicin With Gemtuzumab Ozogamicin Improves Event-Free Survival in Younger Patients With Newly Diagnosed AML and Overall Survival in Patients With NPM1 and FLT3 Mutations
    American Society of Clinical Oncology (ASCO) ; 2024
    In:  Journal of Clinical Oncology Vol. 42, No. 10 ( 2024-04-01), p. 1158-1168
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 42, No. 10 ( 2024-04-01), p. 1158-1168
    Abstract: To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. PATIENTS AND METHODS One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA] ) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). RESULTS There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P 〈 .001) and 3-year event-free survival was higher (57% v 45%; P 〈 .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 ( P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. CONCLUSION Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.23.00943
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2024
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 8
    Online Resource
    Online Resource
    Bendamustine in Patients With Rituximab-Refractory Indolent and Transformed Non-Hodgkin's Lymphoma: Results From a Phase II Multicenter, Single-Agent Study
    American Society of Clinical Oncology (ASCO) ; 2008
    In:  Journal of Clinical Oncology Vol. 26, No. 2 ( 2008-01-10), p. 204-210
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 26, No. 2 ( 2008-01-10), p. 204-210
    Abstract: Bendamustine hydrochloride is an alkylating agent with novel mechanisms of action. This phase II multicenter study evaluated the efficacy and toxicity of bendamustine in patients with B-cell non-Hodgkin's lymphoma (NHL) refractory to rituximab. Patients and Methods Patients received bendamustine 120 mg/m 2 intravenously on days 1 and 2 of each 21-day cycle. Outcomes included response, duration of response, progression-free survival, and safety. Results Seventy-six patients, ages 38 to 84 years, with predominantly stage III/IV indolent (80%) or transformed (20%) disease were treated; 74 were assessable for response. Twenty-four (32%) were refractory to chemotherapy. Patients received a median of two prior unique regimens. An overall response rate of 77% (15% complete response, 19% unconfirmed complete response, and 43% partial) was observed. The median duration of response was 6.7 months (95% CI, 5.1 to 9.9 months), 9.0 months (95% CI, 5.8 to 16.7) for patients with indolent disease, and 2.3 months (95% CI, 1.7 to 5.1) for those with transformed disease. Thirty-six percent of these responses exceeded 1 year. The most frequent nonhematologic adverse events included nausea and vomiting, fatigue, constipation, anorexia, fever, cough, and diarrhea. Grade 3 or 4 reversible hematologic toxicities included neutropenia (54%), thrombocytopenia (25%), and anemia (12%). Conclusion Single-agent bendamustine produced durable objective responses with acceptable toxicity in heavily pretreated patients with rituximab-refractory, indolent NHL. These findings are promising and will serve as a benchmark for future clinical trials in this novel patient population.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2007.12.5070
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2008
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 9
    Online Resource
    Online Resource
    Final results of a phase I/II dose-escalation study of fractionated dose 177 Lu-PSMA-617 for progressive metastatic castration resistant prostate cancer (mCRPC).
    American Society of Clinical Oncology (ASCO) ; 2024
    In:  Journal of Clinical Oncology Vol. 42, No. 16_suppl ( 2024-06-01), p. 5074-5074
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 42, No. 16_suppl ( 2024-06-01), p. 5074-5074
    Abstract: 5074 Background: PC commonly expresses PSMA and has dose-responsive radiosensitivity. 177 Lu-based radioligands usually use an empiric dosing regimen. This 1st dose-escalation study of 177 Lu-PSMA-617 employed a dose-dense fractionation schedule intended to allow delivery of higher total doses to overcome radioresistance due to repopulation. Here, we report mature results of the study. Methods: Progressive mCRPC following 〉 1 potent ARPI (e.g., abi/enza) and chemo (or unfit/refuse taxane) without limit of # prior therapies provided adequate organ function and ECOG PS 0-2. Treatment: single cycle of fractionated dose 177 Lu-PSMA-617 on D1 and D15. In Ph I dose-escalation, patients (pts) received one cycle of 7.4 - 22 GBq followed by Simon 2-stage Ph II at 22.2 GBq. PSMA expression was not required for treatment, but pre- and post-treatment 68 Ga-PSMA11 PET/CT and/or 177 Lu-PSMA-617 SPECT done. Primary efficacy by PSA changes with 2ndary outcomes with CT/bone scans, PSMA PET, circulating tumor cell (CTC; CellSearch) counts, plasma DNA (PCF_SELECT), and survival. Results: Between 1/2017 – 2/2021, 50 pts treated with median PSA 164.3, 35 (70%) CALGB (Halabi) poor risk. 47 (94%) bone, 38 (76%) nodal, 12 (24%) lung, 5 (10%) liver mets (4 additional pts with PSMA PET+ liver mets not apparent on CT). 29 (58%) with prior 〉 2 ARPI, 29 (58%) with 〉 1 chemo, 14 (28%) with Ra-223, 2 (4%) with 177 Lu-J591. 27 (54%) treated at 22 GBq. No dose-limiting toxicity during Ph I. 38 (76%) with any PSA decline, 27 (54%) with 〉 50% PSA. Median rPFS 8.3 mo [5.6-16.7], and OS 15.7 mo [10.9-20.6] . Of 17 RECIST measurable, 6 (35.3%) responded, 7 (41.2%) stable, 4 (23.5%) progressed. Of 31 with paired CTC counts, 16 (52%) decreased, 5 (16%) were stable; 10 (32.3%) converted to favorable/undetectable. Plasma DNA with high allele-specific ploidy and ARcopy number gain associated with OS (univariate). Treatment emergent adverse events (TEAE): 32 (64%) dry mouth, 22 (44%) pain flare, 22 (44%) fatigue, 19 (38%) nausea, 15 (30%) anemia, 15 (28%) thrombocytopenia (plts), 9 (18%) neutropenia (ANC). All TEAEs restricted to grade (Gr) 1-2 except 6 (12%) with Gr 3 anemia, 2 (4%) Gr 3/4 plts, 1 (2%) Gr 3 ANC. TEAE incidence and Gr were not related to dose. On multivariable analysis, 177 Lu dose administered (p=0.09), CALGB risk (p=0.04), prior chemo (p=0.009), associated with OS; dose (p=0.1), CALGB risk (p=0.2), and AR copy number (p=0.2) associated with PSA50 decline. Baseline PSMA imaging (by imaging score or SUVmax) was not associated with OS or response. Conclusions: A single-cycle of fractionated-dose 177Lu-PSMA-617 is safe. Despite no pre-selection for PSMA expression, most had PSA decline with favorable PFS and OS compared to historical controls and similar to PSMA-selected targeted radionuclide studies administering multiple cycles in a less dose-intense approach. Clinical trial information: NCT03042468 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2024.42.16_suppl.5074
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2024
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 10
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    Final results of the McCAVE trial: A double-blind, randomized phase 2 study of vanucizumab (VAN) plus FOLFOX vs. bevacizumab (BEV) plus FOLFOX in patients (pts) with previously untreated metastatic colorectal carcinoma (mCRC).
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 3539-3539
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 3539-3539
    Abstract: 3539 Background: VEGF-A and ANG-2 have complementary roles in regulation of tumor angiogenesis. Targeting VEGF-A with BEV in combination chemotherapy (CT) in mCRC has proven to increase PFS and OS. ANG-2 is overexpressed and associated with poor outcome of mCRC pts receiving BEVcontaining treatment. Hence, dual blockade of VEGF-A and ANG-2 by the bispecific mAb VAN with standard CT may improve clinical activity in mCRC. Methods: All pts received mFOLFOX-6 and were randomized 1:1 to also receive intravenous VAN 2000 mg every other week (Q2W) (Arm A) or BEV 5 mg/kg Q2W (Arm B). The primary end point was investigator assessed progression-free survival (PFS). Key eligibility criteria included pts with non-resectable mCRC, no prior therapy for advanced disease, PS 0-1, adequate organ functions, and no history of GI fistula/perforation or intraabdominal abscess within the last 6 months. Results: 192 pts were randomized (Arms A/B, n = 95/97) by 39 sites in 7 countries, between Oct 2014 and May 2016. Median follow-up was 17.6 months (range 2.8 – 20.7). In the ITT population (n = 189; Arms A/B, n = 94/95), median PFS in Arms A and B was 11.3 and 11.0 months (stratified hazard ratio (HR) 1.00 (95%CI 0.64-1.58; p = 0.985)), respectively. Objective response rate was 52.1% vs 57.9%. Relevant prognostic factors incl. RAS/BRAF status and tumor sidedness were balanced between arms and did not significantly influence outcome. Baseline plasma ANG-2 levels were prognostic in both arms but not predictive for response to VAN. The overall incidence of adverse events (AEs) grade ≥ 3 was similar (Arms A/B, 83.9%/82.1%); AEs grade ≥ 3 attributed to the mode of action of VAN/BEV included hypertension (37.6%/18.9%), hemorrhage (2.2%/1.1%), thromboembolic events (venous 6.5%/2.1%; arterial 1.1%/3.2%) and GI perforations incl. GI fistula & abdominal abscess (10.6%/8.4%). Conclusions: The combination of VAN and FOLFOX did not improve PFS and was associated with a marked increase in hypertension compared with BEV plus FOLFOX. Our results strongly suggest that ANG-2 is not a relevant therapeutic target in the setting of first line mCRC. Clinical trial information: NCT02141295.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.3539
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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