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  • American Society of Clinical Oncology (ASCO)  (8)
  • 1
    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
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 33 ( 2020-11-20), p. 3895-3904
    Abstract: BRAF V600 mutations are commonly found in melanoma and thyroid cancers and to a lesser degree in other tumor types. Subprotocol H (EAY131-H) of the NCI-MATCH platform trial sought to investigate the selective BRAF inhibitor dabrafenib and the MEK1/2 inhibitor trametinib in patients with solid tumors, lymphomas, or multiple myeloma whose tumors harbored a BRAF V600 mutation. PATIENTS AND METHODS EAY131-H is an open-label, single-arm study. Patients with melanoma, thyroid, or colorectal cancer were excluded; patients with non–small-cell lung cancer were later excluded in an amendment. Patients received dabrafenib 150 mg twice per day and trametinib 2 mg per day continuously until disease progression or intolerable toxicity. The primary end point was centrally assessed objective response rate (ORR); secondary end points included progression-free survival (PFS), 6-month PFS, and overall survival. RESULTS Thirty-five patients were enrolled, and 29 were included in the primary efficacy analysis as prespecified in the protocol. Median age was 59 years, and 45% of the patients had received ≥ 3 lines of therapy. The confirmed ORR was 38% (90% CI, 22.9% to 54.9%) with P 〈 .0001 against a null rate of 5%, and PFS was 11.4 months (90% CI, 8.4 to 16.3 months); responses were seen in 7 distinct tumor types. Seven patients had a duration of response of 〉 12 months, including 4 patients with a duration of response of 〉 24 months. An additional 8 patients had a PFS 〉 6 months. The median overall survival was 28.6 months. Reported adverse events were comparable to those noted in previously reported profiles of dabrafenib and trametinib. CONCLUSION This study met its primary end point, with an ORR of 38% ( P 〈 .0001) in this mixed histology, pretreated cohort. This promising activity warrants additional investigations in BRAF V600 -mutated tumors outside of currently approved indications.
    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: 2020
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 3002-3002
    Abstract: 3002 Background: The NCI-MATCH precision medicine trial assigns patients (pts) with solid tumors, lymphomas, or multiple myeloma with progression on prior treatment to a targeted therapy based on genetic alterations identified in pre-treatment biopsies. Arm H (EAY131-H) evaluated the combination of the BRAF inhibitor (inh) dabrafenib (DAB), and the MEK inh, trametinib (TRM), in pts with BRAF V600E/K mutations. Methods: Pts with melanoma, thyroid, or colorectal cancer were excluded. Pts with NSCLC were excluded after the U.S. Food and Drug Administration (FDA) approved DAB/TRM for this indication. Pts received DAB 150 mg po BID and TRM 2 mg PO daily on 28 day cycles until disease progression or intolerable toxicity; restaging was performed every 2 cycles. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), 6-month PFS, and overall survival (OS). Results: A total of 35 pts were enrolled from 1/2016-2/2018; 2 were ineligible (CrCl below criteria; labs out of window). Over 17 distinct tumor histologies were represented. 58% of pts were female, median age was 63 (range 21-85), 94% were Caucasian, and 48% of pts had received at least 3 prior therapies (range 1- 8). The confirmed ORR was 33.3% (90% CI 19.9%, 49.1%), with a median duration of response (DoR) of 12 months (mon). Varied histologies had a DoR of 〉 12 mon: histiocytic sarcoma, cholangiocarcinoma and mixed adenoneuroendocrine carcinoma of unknown primary, among others. Median PFS was 9.4 mon; the 6 mon PFS rate was 70.6% (90% CI 58.2%-85.5%), and an additional 10 pts had a PFS 〉 5.5 mon. Median OS has not been reached. At the time of data cutoff (12/2018) 11 pts continue on treatment. Adverse events (AE) were comparable to previously reported profiles of DAB/TRM; no new AEs were identified. The most frequent grade 3 AEs were fatigue, neutropenia, hyponatremia, hypophosphatemia, and urinary tract infection; there was 1 grade 4 sepsis; no grade 5 AEs. Conclusions: In this pre-treated, mixed histology cohort, DAB and TRM showed promising activity outside of currently approved FDA indications warranting further investigations. Correlative analyses are planned. Clinical trial information: NCT02465060.
    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: 2019
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 10055-10055
    Abstract: 10055 Background: Childhood cancer survivors are a growing population who appear to be at higher risk for premature aging and age-related chronic health conditions than their peers with no history of cancer. Diet affects many hallmarks of aging, such as inflammation, metabolic dysfunctions, and molecular and epigenetic changes, leading to impairment in physical and cognitive functions and premature death. High consumption of animal foods that are high in protein and fat increase risk for many age-related chronic diseases. However, some studies found protein intake was beneficial for physical frailty in elderly and cancer survivors. Methods: Adult survivors ( 〉 = 18 years old) of childhood cancer survivors enrolled in the SJLIFE Cohort between 2007 and 2017 completed a 110-item food frequency questionnaire at study entry (n = 3,322). Survivors’ sociodemographic, cancer, cancer treatments, and medical history data were abstracted from medical records. Health conditions self-reported after cancer diagnosis were clinically validated. Premature aging was assessed using the Deficit Accumulation Index (DAI) based on 45 aging-related health conditions. DAI is categorized into low ( 〈 0.2), medium (0.2-0.34) and high ( 〉 0.35) aging risk groups. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multinomial logistic regressions adjusting for potential confounders. Results: The average age of survivors at baseline was 31 years. Approximately half of the survivors were women, and 82% were white, non-Hispanic. 20% and 8% of survivors were at medium and high risk for aging, respectively. Survivors at high risk for aging tended to be female, smokers, have low socioeconomic status, and received radiation therapy to head and neck, chest, spine or abdomen compared to those at low aging risk. Higher protein intake was associated with a less risk of premature aging (OR = 0.74, 95% CI: 0.58-0.95 for high aging risk group; OR = 0.91, 95% CI: 0.78-1.07 for medium aging risk group, per increment of 5% of total energy intake). On the other hand, higher fat intake was related to an increased risk of premature aging (OR = 1.14, 95% CI: 1.01-1.29 for high aging risk group; OR = 0.99, 95% CI: 0.91-1.08 for medium aging risk group, per increment of 5% of total energy intake). However, substituting monounsaturated fat for other types of fat was associated with a lower risk of premature aging (OR = 0.81 95% CI: 0.70-0.95 for high aging risk group). Red meat (OR = 1.11, 95% CI: 0.87-1.42 for high aging risk group) and dairy intake (OR = 0.99, 95% CI: 0.72-1.38 for high aging risk group) was not related to risk of premature aging. Conclusions: Consuming protein and fat from healthy foods may lower the risk of premature aging in childhood cancer survivors.
    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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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 1 ( 2021-01-01), p. 79-89
    Abstract: Human epidermal growth factor receptor 2 (HER2) targeting plus endocrine therapy (ET) improved clinical benefit in HER2-positive, hormone receptor (HR)–positive metastatic breast cancer (MBC) versus ET alone. Dual HER2 blockade enhances clinical benefit versus single HER2 blockade. The ALTERNATIVE study evaluated the efficacy and safety of dual HER2 blockade plus aromatase inhibitor (AI) in postmenopausal women with HER2-positive/HR-positive MBC who received prior ET and prior neo(adjuvant)/first-line trastuzumab (TRAS) plus chemotherapy. This updated article reflects minor numerical corrections in some secondary efficacy analyses that resulted from programming errors and that do not change the major conclusions of the study. METHODS Patients were randomly assigned (1:1:1) to receive lapatinib (LAP) plus TRAS plus AI, TRAS plus AI, or LAP plus AI. Patients for whom chemotherapy was intended were excluded. The primary end point was progression-free survival (PFS; investigator assessed) with LAP plus TRAS plus AI versus TRAS plus AI. Secondary end points were PFS (comparison of other arms), overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), and safety. RESULTS Three hundred fifty-five patients were included in this analysis: LAP plus TRAS plus AI (n = 120), TRAS plus AI (n = 117), and LAP plus AI (n = 118). Baseline characteristics were balanced. The study met its primary end point; superior PFS was observed with LAP plus TRAS plus AI versus TRAS plus AI (median PFS, 11 v 5.6 months; hazard ratio, 0.62 [95% CI, 0.45 to 0.88]; P = .0063). A consistent PFS benefit was observed in predefined subgroups. ORR, CBR, and OS also favored LAP plus TRAS plus AI. The median PFS with LAP plus AI versus TRAS plus AI was 8.3 versus 5.6 months (hazard ratio, 0.85 [95% CI, 0.62 to 1.17] ; P = .3159). Common adverse events (AEs; ≥ 15%) with LAP plus TRAS plus AI, TRAS plus AI, and LAP plus AI were diarrhea (69%, 9%, and 51%, respectively), rash (36%, 2%, and 28%, respectively), nausea (22%, 9%, and 22%, respectively), and paronychia (30%, 0%, and 15%, respectively), mostly grade 1 or 2. Serious AEs were reported similarly across the 3 groups, and AEs leading to discontinuation were lower with LAP plus TRAS plus AI. CONCLUSION Dual HER2 blockade with LAP plus TRAS plus AI showed superior PFS benefit versus TRAS plus AI in patients with HER2-positive/HR-positive MBC. This combination offers an effective and safe chemotherapy-sparing alternative treatment regimen for this patient population.
    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: 2021
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 8 ( 2018-03-10), p. 741-748
    Abstract: Human epidermal growth factor receptor 2 (HER2) targeting plus endocrine therapy (ET) improved clinical benefit in HER2-positive, hormone receptor (HR)–positive metastatic breast cancer (MBC) versus ET alone. Dual HER2 blockade enhances clinical benefit versus single HER2 blockade. The ALTERNATIVE study evaluated the efficacy and safety of dual HER2 blockade plus aromatase inhibitor (AI) in postmenopausal women with HER2-positive/HR-positive MBC who received prior ET and prior neo(adjuvant)/first-line trastuzumab (TRAS) plus chemotherapy. Methods Patients were randomly assigned (1:1:1) to receive lapatinib (LAP) + TRAS + AI, TRAS + AI, or LAP + AI. Patients for whom chemotherapy was intended were excluded. The primary end point was progression-free survival (PFS; investigator assessed) with LAP + TRAS + AI versus TRAS + AI. Secondary end points were PFS (comparison of other arms), overall survival, overall response rate, clinical benefit rate, and safety. Results Three hundred fifty-five patients were included in this analysis: LAP + TRAS + AI (n = 120), TRAS + AI (n = 117), and LAP + AI (n = 118). Baseline characteristics were balanced. The study met its primary end point; superior PFS was observed with LAP + TRAS + AI versus TRAS + AI (median PFS, 11 v 5.7 months; hazard ratio, 0.62; 95% CI, 0.45 to 0.88; P = .0064). Consistent PFS benefit was observed in predefined subgroups. Overall response rate, clinical benefit rate, and overall survival also favored LAP + TRAS + AI. The median PFS with LAP + AI versus TRAS + AI was 8.3 versus 5.7 months (hazard ratio, 0.71; 95% CI, 0.51 to 0.98; P = .0361). Common adverse events (AEs; ≥ 15%) with LAP + TRAS + AI, TRAS + AI, and LAP + AI were diarrhea (69%, 9%, and 51%, respectively), rash (36%, 2%, and 28%, respectively), nausea (22%, 9%, and 22%, respectively), and paronychia (30%, 0%, and 15%, respectively), mostly grade 1 or 2. Serious AEs were reported similarly across the three groups, and AEs leading to discontinuation were lower with LAP + TRAS + AI. Conclusion Dual HER2 blockade with LAP + TRAS + AI showed superior PFS benefit versus TRAS + AI in patients with HER2-positive/HR-positive MBC. This combination offers an effective and safe chemotherapy-sparing alternative treatment regimen for this patient population.
    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
    detail.hit.zdb_id: 2005181-5
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 1004-1004
    Abstract: 1004 Background: Combination ofHER2-targeted therapy+AI improved clinical benefit in patients (pts) with HER2+, HR+ MBC vs AI alone in two previous trials, median progression free survival (mPFS) 4.8 vs 2.4 mo (TAnDEM), and 8.2 vs 3.0 mo (EGF30008). Dual HER2 blockade enhances clinical benefit vs single HER2 blockade. This study evaluated the safety and efficacy of dual vs single HER2 blockade (L+T vs T/L)+AI in HER2+, HR+ MBC progressing on (neo)adjuvant/first-line T+chemotherapy (CT). HER2 and HR status were assessed for eligibility at local lab. Methods: PMW were randomized 1:1:1 to receive T (8mg/kg followed by 6mg/kg IV Q3W)+L (1000mg/d)+AI or T+AI or L (1500mg/d)+AI. AI was per investigator’s choice. Pts were excluded if they were intended for CT. The primary endpoint was to assess superiority of PFS with L+T vs T. Secondary endpoints included PFS (L vs T), overall survival (OS), overall response rate (ORR), and safety. Results: 369 pts were enrolled; current analysis included 355 pts (data cutoff, March 11, 2016); L+T (n = 120), T (n = 117) or L (n = 118). Final PFS data were analyzed after 137 events. Baseline characteristics were balanced across all treatment (tx) arms. The primary endpoint was met; superior PFS was observed with L+T vs T (mPFS, 11 vs 5.7 mo; HR = 0.62, 95% CI [0.45, 0.88], P= 0.0064). This benefit of L+T was consistent in key subgroups. mPFS with L vs T was 8.3 vs 5.7 mo (HR = 0.71, 95% CI [0.51, 0.98] , P= 0.0361). ORR with L+T, T, and L was 32%, 14%, and 19% respectively. OS data are immature. Most common adverse events (AEs) with L+T, T and L (≥15%, any arm) were diarrhea (69%, 9%, 51%), rash (36%, 2%, 28%), nausea (22%, 9%, 22%), and paronychia (30%, 0, 15%). Hepatic abnormalities of 〉 3 ULN ALT/AST levels were noted in 4%, 6%, and 16% respectively. Incidence of tx-related SAEs was 5%, 2%, and 4% and on-tx deaths was 3%, 4%, and 5%, respectively. Conclusions: Dual HER2 blockade with L+T+AI showed superior PFS benefit vs T+AI, in pts with HER2+, HR+ MBC. Incidence of AEs was increased with L+T. This combination can potentially offer an effective CT-sparing tx option in subgroup of HER2+, HR+ pts without aggressive disease and who are not candidates for CT. Clinical trial information: 2010-019577-16.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 34_suppl ( 2018-12-01), p. 39-39
    Abstract: 39 Background: Environment is important component of communication skills. Physicians’ communication style including attire may influence patient perceptions. Previous studies mostly based on pictures of providers in different attires provide conflicting evidence. This RCT aimed to explore the effects of physician attire on patients’ perceptions of compassion, professionalism and physician preference. Hypothesis was that patients will perceive the doctor in formal attire as more compassionate than the doctor wearing casual attire. Methods: 105 English speaking adult follow-ups at outpatient supportive care center, were randomized to watch 2 standardized, 3-minute video vignettes, with similar script, depicting a routine clinic encounter. In one video, physician was wearing formal attire with tie and buttoned up white coat, while in the other, physician was in casual attire without a tie or white coat. Actors and patients were all blinded to purpose of the study. Investigators were blinded to the videos watched by patients. After viewing each video, patients completed validated questionnaires rating their perception of physician compassion (0 = best, 50 = worst) and professionalism (5 = poor, 25 = very good). Patients were also asked to rate their preference for the physician. Results: There were no significant differences between formal and casual attire for compassion [median (IQR), 25 (10, 31) vs 20 (8, 27); P = 0.31] and professionalism, [17 (13, 21) vs 18 (14, 22); P = 0.42] . 32 (30%) patients preferred formal, 33 (31%) preferred casual attire and 40 (38 %) patients had no preference. Subgroup analysis did not show significant differences among age, sex, marital status and education level for compassion, professionalism and physician preference. Conclusions: Doctor’s attire did not have an effect on patients’ perception of physicians’ level of compassion and professionalism. Dress code also did not influence the patients’ preference for their doctor or their trust and confidence in the doctor’s ability to provide care. There is need for more RCTs in area of communication skills specifically to better understand the impact of different attires on patient perceptions. Clinical trial information: NCT03168763.
    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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