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  • American Society of Clinical Oncology (ASCO)  (16)
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 650-650
    Abstract: 650 Background: Management of metastatic renal cell carcinoma (mRCC) is highly individualized and often involves cytoreductive nephrectomy (CN) and systemic therapy (ST). The optimal sequencing of CN and ST is uncertain. A difference in perioperative outcomes based on sequence of CN and ST could influence decision-making. We conducted this NSQIP analysis to assess whether preoperative systemic therapy adversely impacted perioperative outcomes in patients receiving deferred CN. Methods: This analysis was conducted using the American College of Surgeons NSQIP Participant Use Data File for years 2019 and 2020. These years were selected because data on receipt of preoperative therapy is only available since 2019. Inclusion criteria were i) CPT code consistent with nephrectomy, ii) urologist operating surgeon & iii) presence of disseminated cancer. All cases with ICD-10 diagnosis codes not consistent with mRCC were excluded. Groups were stratified by their receipt of preoperative systemic therapy within 90 days before CN and we assessed 46 preoperative and perioperative outcomes. Results: The study cohort included 505 patients with 115 (23%) who received preoperative ST. No differences were noted in perioperative outcomes (Table). Patients receiving preoperative ST were more likely to be on steroids (23% vs. 7%, p 〈 0.01) and develop urinary tract infections (4.3% vs. 0.5%, p 〈 0.01). There were no significant differences noted in other related variables like surgical site infections, wound dehiscence, sepsis, septic shock, pneumonia, cardiovascular complications, preoperative hypertension, or preoperative diabetes (p 〉 0.05). Conclusions: Because preoperative ST did not have an appreciable impact on deferred CN perioperative outcomes, decision making for ST and CN sequencing should not be influenced by perioperative outcomes. Those who undergo deferred CN are unlikely to experience delayed time to surgery or perioperative complications from their ST. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO)
    Abstract: Platinum-based doublets with concurrent and maintenance bevacizumab are standard therapy for ovarian cancer (OC) relapsing after a platinum-free interval (PFI) 〉 6 months. Immunotherapy may be synergistic with bevacizumab and chemotherapy. PATIENTS AND METHODS ATALANTE/ENGOT-ov29 (ClinicalTrials.gov identifier: NCT02891824 ), a placebo-controlled double-blinded randomized phase III trial, enrolled patients with recurrent epithelial OC, one to two previous chemotherapy lines, and PFI 〉 6 months. Eligible patients were randomly assigned 2:1 to atezolizumab (1,200 mg once every 3 weeks or equivalent) or placebo for up to 24 months, combined with bevacizumab and six cycles of chemotherapy doublet, stratified by PFI, PD-L1 status, and chemotherapy regimen. Coprimary end points were investigator-assessed progression-free survival (PFS) in the intention-to-treat (ITT) and PD-L1–positive populations (alpha .025 for each population). RESULTS Between September 2016 and October 2019, 614 patients were randomly assigned: 410 to atezolizumab and 204 to placebo. Only 38% had PD-L1–positive tumors. After 3 years' median follow-up, the PFS difference between atezolizumab and placebo did not reach statistical significance in the ITT (hazard ratio [HR], 0.83; 95% CI, 0.69 to 0.99; P = .041; median 13.5 v 11.3 months, respectively) or PD-L1–positive (HR, 0.86; 95% CI, 0.63 to 1.16; P = .30; median 15.2 v 13.1 months, respectively) populations. The immature overall survival (OS) HR was 0.81 (95% CI, 0.65 to 1.01; median 35.5 v 30.6 months with atezolizumab v placebo, respectively). Global health-related quality of life did not differ between treatment arms. Grade ≥3 adverse events (AEs) occurred in 88% of atezolizumab-treated and 87% of placebo-treated patients; grade ≥3 AEs typical of immunotherapy were more common with atezolizumab (13% v 8%, respectively). CONCLUSION ATALANTE/ENGOT-ov29 did not meet its coprimary PFS objectives in the ITT or PD-L1–positive populations. OS follow-up continues. Further research on biopsy samples is warranted to decipher the immunologic landscape of late-relapsing OC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: American Society of Clinical Oncology Educational Book, American Society of Clinical Oncology (ASCO), , No. 41 ( 2021-06), p. e339-e353
    Abstract: Optimizing the well-being of the oncology clinician has never been more important. Well-being is a critical priority for the cancer organization because burnout adversely impacts the quality of care, patient satisfaction, the workforce, and overall practice success. To date, 45% of U.S. ASCO member medical oncologists report experiencing burnout symptoms of emotional exhaustion and depersonalization. As the COVID-19 pandemic remains widespread with periods of outbreaks, recovery, and response with substantial personal and professional consequences for the clinician, it is imperative that the oncologist, team, and organization gain direct access to resources addressing burnout. In response, the Clinician Well-Being Task Force was created to improve the quality, safety, and value of cancer care by enhancing oncology clinician well-being and practice sustainability. Well-being is an integrative concept that characterizes quality of life and encompasses an individual's work- and personal health–related environmental, organizational, and psychosocial factors. These resources can be useful for the cancer organization to develop a well-being blueprint: a detailed start plan with recognized strategies and interventions targeting all oncology stakeholders to support a culture of community in oncology.
    Type of Medium: Online Resource
    ISSN: 1548-8748 , 1548-8756
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2431126-1
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 23 ( 2013-08-10), p. 2927-2935
    Abstract: Reports detailing the prognostic impact of TP53 mutations in medulloblastoma offer conflicting conclusions. We resolve this issue through the inclusion of molecular subgroup profiles. Patients and Methods We determined subgroup affiliation, TP53 mutation status, and clinical outcome in a discovery cohort of 397 medulloblastomas. We subsequently validated our results on an independent cohort of 156 medulloblastomas. Results TP53 mutations are enriched in wingless (WNT; 16%) and sonic hedgehog (SHH; 21%) medulloblastomas and are virtually absent in subgroups 3 and 4 tumors (P 〈 .001). Patients with SHH/TP53 mutant tumors are almost exclusively between ages 5 and 18 years, dramatically different from the general SHH distribution (P 〈 .001). Children with SHH/TP53 mutant tumors harbor 56% germline TP53 mutations, which are not observed in children with WNT/TP53 mutant tumors. Five-year overall survival (OS; ± SE) was 41% ± 9% and 81% ± 5% for patients with SHH medulloblastomas with and without TP53 mutations, respectively (P 〈 .001). Furthermore, TP53 mutations accounted for 72% of deaths in children older than 5 years with SHH medulloblastomas. In contrast, 5-year OS rates were 90% ± 9% and 97% ± 3% for patients with WNT tumors with and without TP53 mutations (P = .21). Multivariate analysis revealed that TP53 status was the most important risk factor for SHH medulloblastoma. Survival rates in the validation cohort mimicked the discovery results, revealing that poor survival of TP53 mutations is restricted to patients with SHH medulloblastomas (P = .012) and not WNT tumors. Conclusion Subgroup-specific analysis reconciles prior conflicting publications and confirms that TP53 mutations are enriched among SHH medulloblastomas, in which they portend poor outcome and account for a large proportion of treatment failures in these patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 5 ( 2022-02-10), p. 449-458
    Abstract: The PALLAS study investigated whether the addition of palbociclib, an oral CDK4/6 inhibitor, to adjuvant endocrine therapy (ET) improves invasive disease-free survival (iDFS) in early hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) breast cancer. In this analysis, we evaluated palbociclib exposure and discontinuation in PALLAS. METHODS Patients with stage II-III HR+, HER2– disease were randomly assigned to 2 years of palbociclib with adjuvant ET versus ET alone. The primary objective was to compare iDFS between arms. Continuous monitoring of toxicity, dose modifications, and early discontinuation was performed. Association of baseline covariates with time to palbociclib reduction and discontinuation was analyzed with multivariable competing risk models. Landmark and inverse probability weighted per-protocol analyses were performed to assess the impact of drug persistence and exposure on iDFS. RESULTS Of the 5,743 patient analysis population (2,840 initiating palbociclib), 1,199 (42.2%) stopped palbociclib before 2 years, the majority (772, 27.2%) for adverse effects, most commonly neutropenia and fatigue. Discontinuation of ET did not differ between arms. Discontinuations for non–protocol-defined reasons were greater in the first 3 months of palbociclib, and in the first calendar year of accrual, and declined over time. No significant relationship was seen between longer palbociclib duration or ≥ 70% exposure intensity and improved iDFS. In the weighted per-protocol analysis, no improvement in iDFS was observed in patients receiving palbociclib versus not (hazard ratio 0.89; 95% CI, 0.72 to 1.11). CONCLUSION Despite observed rates of discontinuation in PALLAS, analyses suggest that the lack of significant iDFS difference between arms was not directly related to inadequate palbociclib exposure. However, the discontinuation rate illustrates the challenge of introducing novel adjuvant treatments, and the need for interventions to improve persistence with oral cancer therapies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 1039-1039
    Abstract: 1039 Background: Hormone tx (HT) is the primary 1L tx for ER+ ABC. In the PALOMA-2 study (NCT01740427), PAL+L as 1L ABC tx prolonged progression-free survival (PFS; hazard ratio [HR] 0.58; P 〈 .001) (Finn et al, NEJM. 2016). Methods: Postmenopausal pts with ER+/HER2– ABC and no prior systemic treatment in the advanced setting were randomized 2:1 to PAL (125 mg/d oral [3 wk on, 1 wk off]) + L (2.5 mg QD) or placebo (P) + L. Key endpoints were investigator-assessed PFS and safety. Results: 666pts (444, PAL+L; 222, P+L) were enrolled. Pts were similarly distributed between arms for visceral (48%) and nonvisceral (52%) disease and prior HT (56%) and no prior HT (44%); more pts had disease-free interval (DFI) 〉 12 mo (40%) than ≤12 mo (22%). Median PFS (mPFS) was improved in all subgroups by adding PAL to L (Table). Adverse events were consistent across subgroups, as described for the full study population. Conclusions: PAL+L improved mPFS vs P+L with manageable toxicity across all subgroups including those with visceral disease. PAL+L provides a 1L option that should be considered for all pts with ER+/HER2- ABC. Sponsor: Pfizer Clinical trial information: NCT01740427. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 8 ( 2018-03-10), p. 773-779
    Abstract: Nivolumab provides clinical benefit (objective response rate [ORR], 31%; 95% CI, 20.8 to 42.9; disease control rate, 69%; 12-month overall survival [OS] , 73%) in previously treated patients with DNA mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) metastatic colorectal cancer (mCRC); nivolumab plus ipilimumab may improve these outcomes. Efficacy and safety results for the nivolumab plus ipilimumab cohort of CheckMate-142, the largest single-study report of an immunotherapy combination in dMMR/MSI-H mCRC, are reported. Patients and Methods Patients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks. Primary end point was investigator-assessed ORR. Results Of 119 patients, 76% had received ≥ two prior systemic therapies. At median follow-up of 13.4 months, investigator-assessed ORR was 55% (95% CI, 45.2 to 63.8), and disease control rate for ≥ 12 weeks was 80%. Median duration of response was not reached; most responses (94%) were ongoing at data cutoff. Progression-free survival rates were 76% (9 months) and 71% (12 months); respective OS rates were 87% and 85%. Statistically significant and clinically meaningful improvements were observed in patient-reported outcomes, including functioning, symptoms, and quality of life. Grade 3 to 4 treatment-related adverse events (AEs) occurred in 32% of patients and were manageable. Patients (13%) who discontinued treatment because of study drug-related AEs had an ORR (63%) consistent with that of the overall population. Conclusion Nivolumab plus ipilimumab demonstrated high response rates, encouraging progression-free survival and OS at 12 months, manageable safety, and meaningful improvements in key patient-reported outcomes. Indirect comparisons suggest combination therapy provides improved efficacy relative to anti–programmed death-1 monotherapy and has a favorable benefit-risk profile. Nivolumab plus ipilimumab provides a promising new treatment option for patients with dMMR/MSI-H mCRC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 2527-2527
    Abstract: 2527 Background: Nanoscale metal−organic frameworks (MOFs) are a new class of organic−inorganic hybrid nanomaterials constructed from metal centers and organic ligands. Preclinical studies have shown that nanoscale MOFs can enhance the antitumor effects of ionizing radiation via a unique radiotherapy-radiodynamic therapy mode of action, and MOFs plus radiation can enhance the immunotherapeutic effects of immune checkpoint inhibitors. RiMO-301 is a hafnium-based MOF which enhances radiotherapy and checkpoint blockade immunotherapy without showing systemic toxicity in preclinical models. RiMO-301 is the first MOF to enter clinical trials on human patients. Methods: This is a multicenter, open-label, first-in-human dose-escalation phase I trial of RiMO-301 [NCT03444714]. The primary objective is to determine the maximum tolerated dose (MTD) of locally injected RiMO-301 with or without the PD-1 inhibitor pembrolizumab in patients treated with concurrent palliative doses of radiation (20 Gy in 5 fractions or 30 Gy in 10 fractions) using a 3+3 design. The MTD is defined as the dose associated with dose-limiting toxicity (DLT) in less than 33% of patients. The secondary objective is to evaluate antitumor response (objective response rate, ORR) using RECIST and itRECIST criteria. Results: A total of 25 patients were enrolled and treated with escalating doses of RiMO-301 (relative to tumor volumes). No protocol defined DLT was reported. The observed possibly treatment related adverse events included mild dermatitis radiation, mild dysgeusia, diarrhea, mild hypotension (30 days post treatment) and mild dizziness (30 days post treatment). One patient each experienced a Grade 2 alanine aminotransferase increase 45 days post treatment, a Grade 2 dry mouth, and a Grade 3 pain at the injection site. Nineteen patients were evaluable, with 13 and 6 patients, respectively, for RiMO-301 without and with pembrolizumab treatments. By itRECIST criteria, RiMO-301 without pembrolizumab demonstrated 38.5% (5/13) ORR (1 complete response and 4 partial responses) with 2 additional patients experiencing 20-30% tumor size reduction. RiMO-301 with pembrolizumab exhibited 66.7% (4/6) ORR with the 2 remaining patients showing 15-20% tumor size reduction. Preliminary pharmacokinetic analysis indicated that the hafnium concentrations in the systemic circulation were either below or barely above the level of detection. Conclusions: RiMO-301 with or without pembrolizumab was well tolerated and demonstrated promising signs of efficacy in patients with advanced tumors when treated with concurrent palliative radiotherapy. The results support the use of RiMO-301 as a potential radio-enhancer and will prompt further phase 2 studies in the development of RiMO-301 for patients undergoing radiotherapy. Clinical trial information: NCT03444714 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. 507-507
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 5516-5516
    Abstract: 5516 Background: Patients with platinum-sensitive recurrent OC are often retreated with CbP due to limited treatment options. Ombrabulin (AVE8062), a combretastatin A4 analog, is a vascular disrupting agent that damages established tumor vasculature causing tumor necrosis and has synergistic antitumor activity with platinum agents in vivo (Cancer Sci. 2003;94:200). OPSALIN evaluated whether adding ombrabulin to CbP improves outcomes in patients with platinum-sensitive recurrent OC (NCT01332656; EFC10260). Methods: Patients (aged ≥18 yrs, ECOG PS ≤2) with platinum-sensitive measurable ovarian, fallopian tube, or primary peritoneum carcinoma after completion of one line of platinum-based chemotherapy received ombrabulin 35 mg/m² or Pbo plus CbP (AUC 5–6, 175 mg/m²) every 3 weeks. Randomization (1:1) was stratified by time of first disease recurrence (6–12 or 〉 12 months). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate (RR), and safety. An interim analysis after ~54 PFS events (60% of the target 90 PFS events) was planned. Results: From May 2011 to August 2012, 154 patients were randomized (n=77 in each group). Groups were balanced in terms of baseline characteristics. Overall, the median age was 56 yrs (range 34–79), 93% had ovarian primary tumors, and 54% had first disease recurrence 〉 12 months. Planned interim analysis was performed after 53 PFS events (27 ombrabulin; 26 Pbo); median follow-up was 6.8 months. Ombrabulin did not improve PFS vs Pbo in any subgroup (global median 8.4 vs 10.4 months, respectively; HR 1.33; 60%CI 1.06–1.69). Overall, RR was 65% for ombrabulin and 71% for Pbo. Safety profiles were comparable; rates of grade 3–4 adverse events were 51% for ombrabulin and 41% for Pbo, with no particular safety signals. Conclusions: This interim analysis has suggested no safety concerns or efficacy advantage of adding ombrabulin to CbP in patients with platinum-sensitive recurrent OC. The study was discontinued due to limited probability of the ombrabulin arm showing PFS superiority at the final analysis. Study sponsored by Sanofi. Clinical trial information: NCT01332656.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
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