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  • American Society of Clinical Oncology (ASCO)  (19)
  • 11
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 4_suppl ( 2020-02-01), p. 709-709
    Abstract: 709 Background: Olaparib is a potent inhibitor of PARP-1, which has a critical role in signalling DNA single strand breaks (SSB) as part of the base excision repair pathway, and may have radio-sensitizing effects due to impaired resolution of radiation induced SSB. We hypothesize that O may potentiate the effects of X-CRT in pts with LAPC. Methods: Eligible pts with LAPC, ECOG 〈 1, tumor diameter 〈 6cm, with stable disease (SD) or response after 12 weeks’ induction chemotherapy, were treated with 1 of 4 escalating doses of O given bid po starting on day -3, and then in combination with X (830 mg/m2 bid) and radiation (50·4 Gy in 28 fractions) all administered Mon-Fri. Dose limiting toxicities (DLT) were determined on clinical and lab toxicity assessments (NCI-CTC AE v4.03) performed weekly from the start of O until completion of O plus X-CRT (i.e. 6 weeks). Dose escalation continued with a rolling-six design until the Maximum Tolerated Dose (MTD) was reached. Blood samples for PK analyses of O and PD measurement (inhibition of PARP activity) were collected on day -3 (O monotherapy) and during week 1 of O + X-CRT. Results: 18 pts, (9 m, 9 f, ECOG 0/1 [n=6/12] ), age range 49-81 (median=70) years, with histologic (14) or cytologic (4) proven LAPC, had received induction chemotherapy with gemcitabine [GEM] (n=2), GEM + X (12), or FOLFIRINOX (3) with partial response (n=4) or stable disease (14). Pts received 50 (3), 100 (4), 150 (6), or 200 (5) mgs bid of O with X+CRT. DLTs were observed in 2 pts (both at 200mgs bid): 1 pt with grade 3 nausea (on optimal anti-emetics) and grade 3 fatigue, 1 pt with grade 3 anorexia. 6 pts were subsequently recruited at 150mgs bid with no DLTs. No pts had complete response, 2 pts had partial response (1 pt each at 100 and 150 mgs bid) and 1 pt (at 100 mgs bid) had progressive disease; the remaining 14 pts had SD. Conclusions: The recommended dose (RP2) of O is 150mgs bid when given in combination with X + CRT in LAPC. Recruitment of up to 12 pts with borderline operable LAPC at the RP2 is ongoing. PK analyses of O, PD studies (PARP inhibition – PBMCs; cytokeratin 18 – serum; γH2AX foci – hair follicles), and exploratory predictive marker studies (tumor – NGS; RNA exome sequencing) are ongoing. Clinical trial information: ISRCTN10361292.
    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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  • 12
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e16755-e16755
    Abstract: e16755 Background: Only a minority of pancreatic cancer patients (pts) are surgical candidates at presentation. Neoadjuvant chemotherapy (NAT) is proposed to increase the proportion of surgical candidates. This study investigates the impact of NAT in routine care of pancreatic cancer. Three cohorts were analysed, patients with early-stage resectable (ER), borderline resectable (BR) and locally advanced (LA) pancreatic cancer. Within these groups, survival outcomes of those undergoing immediate resection (IR) was compared to those receiving NAT with nab-paclitaxel and Gemcitabine (nabPGem) and NAT with FOLFIRINOX. Methods: The PURPLE registry consists of 1492 pancreatic cancer pts from 27 hospitals in Australia, New-Zealand and Singapore, collated between 2016-2019. After exclusion of LA unresectable and metastatic pts (n = 809), 683 pts were included. Kaplan-Meir curves estimated survival between groups with 95% confidence intervals. Multivariable cox proportional hazards models adjusted for age, gender and ECOG performance status. Results: Of 683 pts, 107 received NAT and 576 underwent IR. Those in the NAT group had favourable characteristics, including younger age (mean 63 vs. 66 yrs, p 〈 0.01) and higher proportion of ECOG 0 vs. ≥1 (64% vs 46%) than those undergoing IR. Of those that received NAT, 64 received FOLFIRINOX and 35 nabPGem. Those receiving FOLFIRINOX were younger (mean: 60 vs. 67 yrs, p 〈 0.01) and were more likely ECOG 0 compared to those receiving nabPGem (72% vs. 46%, p = 0.02). Resection rates for pts undergoing IR vs. NAT were 88% vs. 50% in ER and 16% vs. 43% in BR. Rates of R0 resection margins in pts undergoing IR vs. NAT were 54% vs. 25% in ER and 6% vs. 21% in BT. Comparing ER to BR, mOS was 29.9 vs. 20.3 mths (HR: 0.54, p 〈 0.01). Within BR, mOS was 20.3 vs. 17.2 mths for NAT vs. IR (HR: 1.11, p = 0.74). Comparing those receiving FOLFIRINOX vs. nabPGem over all groups, mOS was 22 mths vs. 12 mths (HR: 0.31, p 〈 0.01). Conclusions: Real-world data confirms the use of NAT remains infrequent in this Asia-Pacific population. The use of FOLFIRINOX was associated with better survival than nabPGem based on this observational study. Improved methods for treatment selection are required. Potential biomarkers including circulating tumor DNA are being explored in the DYNAMIC-Pancreas clinical trial.
    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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  • 13
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. e14071-e14071
    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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  • 14
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e18723-e18723
    Abstract: e18723 Background: Chemotherapy at the end of life (CEOL) is widely accepted as an indicator of aggressive care. However, the evidence is limited primarily to single-centre experiences, with no consensus regarding acceptable benchmarks for CEOL, nor how this may be changing over time and with novel treatment options. We describe ‘real world’ CEOL in two large, multisite Australian registries of metastatic colorectal cancer (mCRC) and both locally advanced and metastatic pancreatic cancer (PC). Methods: Data was analysed from the TRACC and PURPLE registries, two large prospective multisite Australian cancer registries collecting prospective demographic, tumour, treatment and outcome data for mCRC and PC respectively. We identified all decedents between May 2009 and November 2020, determined the proportion who died within 14 or 30 days of chemotherapy (14D / 30D), or within 30D after a new line of therapy, defined as the first cycle of a new treatment regimen. Using univariate analysis, we compared baseline demographic and clinicopathological variables and trends over time. Results: 1505 mCRC and 602 PC decedents were identified. 20.9% of decedents (21.6% mCRC and 19.3% PC) received chemotherapy within 30D, and 11.5% within 14D (12.3% mCRC and 9.6% PC). There were lower rates of 30D CEOL after the first cycle of a new line of therapy (4.3% mCRC and 5.7% PC). Rates of CEOL decreased over the study period for mCRC (median rate of initial 3-year period 28% versus 15% in last 3-year period), but remained largely static for PC (18.9% versus 17.9%). 30D CEOL was more likely with palliative than curative intent treatment (mCRC OR 1.6, 95% CI 1.14-2.25, p = 0.007, PC OR 5.3, 95% CI 1.6-17.8), and advanced rather than local disease in PC (PC OR 2.59, 95%CI 1.6-4.1, p 〈 0.001). There was a trend towards CEOL and poorer performance status (ECOG) across all groups, only significant for 30D CEOL mCRC (OR 1.51, 95% CI 1.04-2.2). There was no association between CEOL and patient age, gender, Charlson comorbidity score or lines of therapy. Conclusions: Real-world rates of CEOL are higher in our cohorts of mCRC and PC patients than historical benchmarks but comparable to contemporary reports, which may be due to a wider array of available active treatments. Overall rates are decreasing over time for mCRC but static for PC, which may reflect the poorer overall survival for PC and lack of new effective therapies. The lower rates of death after new lines of therapy may signify that CEOL is more likely with existing treatment regimens and that clinicians are less likely to initiate a new chemotherapeutic regimen at EOL.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 15
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e18733-e18733
    Abstract: e18733 Background: Cancer and systemic anti-cancer treatment (SACT) have been identified as possible risk factors for infection and related severe illness associated with SARS-CoV-2 virus as a consequence of immune suppression. The Scottish COVID CAncer iMmunity Prevalence (SCCAMP) study aimed to characterise the incidence and outcomes of SARS-Cov-2 infection in patients undergoing active anti-cancer treatment during the COVID-19 pandemic and their antibody response following vaccination. Methods: Eligible patients were those attending secondary care for active anti-cancer treatment for a solid tumour. Blood samples were taken for total SARS-CoV-2 antibody assay (Siemens) at baseline and after 1.5, 3, 6 and 12 months. Data on COVID-19 infection, vaccination, cancer type, treatment and outcome (patient death) was obtained from routine electronic health records. Results: The study recruited 766 eligible participants between 28th May 2020 and 31st October 2021. During the study period there were 174 deaths (22%). The median age was 63 years, and 67% were female. Most received cytotoxic chemotherapy (79%), with the remaining 14% receiving immunotherapy and 7% receiving another form of anti-cancer therapy (radiotherapy, other systemic anti-cancer treatment). 48 (6.3%) tested positive for SARS-CoV-2 by PCR during the study period. The overall infection rate matched that of the local adult general population until May 2021, after which population levels appeared higher than the study population. Antibody testing detected additional evidence of infection prior to vaccination, taking the total number to 58 (7.6%). There was no significant difference in SARS-CoV-2 PCR positive test rates based on type of anti-cancer treatment. Mortality rates were similar between those who died within 90 days of a positive SARS-CoV-2 PCR and those with no positive PCR (10.4% vs 10.6%). Death from all causes was lowest among vaccinated patients, and of the patients who had a positive SARS-CoV-2 PCR at any time, all of those who died during the study period were unvaccinated. Multivariate analysis correcting for age, gender, socioeconomic status, Charlson co-morbidity score and number of previous medications revealed that vaccination was associated with a significantly lower infection rate regardless of treatment with chemotherapy or immunotherapy with hazard ratios of 0.307 (95% CI 0.144-0.6548) or 0.314 (95% CI 0.041-2.367) in vaccinated patients respectively. Where antibody data was available, 96.3% of patients successfully raised SARS-CoV-2 antibodies at a time point after vaccination. This was unaffected by treatment type. Conclusions: SCCAMP provides real-world evidence that patients with cancer undergoing SACT have a high antibody response and protection from SARS-CoV-2 infection following COVID-19 vaccination.
    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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  • 16
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. e15131-e15131
    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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  • 17
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 4531-4531
    Abstract: 4531 Background: Standard chemotherapy for advanced germ cell tumors is 3-weekly BEP (bleomycin, etoposide, cisplatin). 5-year overall survival is 〉 90% in good risk disease, but only ~80% in intermediate and ~ 60% in poor risk disease. Accelerated versions of standard regimens have proven more effective in other malignancies. We aimed to determine tolerability and activity of accelerated (2-weekly) BEP by combining data from two single arm, multi-center, phase I/II trials. Methods: The UK trial (n=16) included patients with intermediate and poor risk metastatic germ cell tumours. The Australian trial (n=45) also included patients with radiologically measurable good risk disease. BEP chemotherapy was repeated every 2 weeks for 4 cycles (3 cycles for good risk). The Australian and UK regimens differed for cisplatin (20mg/m 2 D1-5; 50mg/m 2 D1-2), etoposide (100mg/m 2 D1-5; 165mg/m 2 D1-3), bleomycin (30kIU weekly x 12 or 9; 30kIU at 4-6 day intervals x 12), and pegylated G-CSF (6mg D6; 6mg D4) respectively. Primary endpoint for combined analysis was 2-year progression-free survival. Results: 61 patients were enrolled from 2004-09 (UK) and 2008-10 (Australia). 17 had poor risk, 28 intermediate risk, 16 good risk disease. Median follow-up is 27 months (range 6 to 81). Adverse events are presented in the table. 45 of 61 patients (74%) achieved a complete response to chemotherapy +/- surgery (9 of 17 poor risk (53%), 20 of 28 intermediate risk (71%), 16 of 16 good risk disease (100%)). 11 of 61 patients have relapsed. 2 patients have died of disease (both intermediate risk). 2 year overall survival is 98%. 2 year progression-free survival is 65% for poor risk, 86% for intermediate risk, and 92% for good risk disease. Conclusions: Efficacy data are promising, particularly for intermediate and poor risk disease. Adverse events appear comparable to standard BEP. These results provide the rationale for an international trial randomised trial comparing accelerated and standard versions of BEP. [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: 2012
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  • 18
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 3_suppl ( 2021-01-20), p. 386-386
    Abstract: 386 Background: Current standard combination first line palliative chemotherapy regimens in advanced pancreatic ductal adenocarcinoma (PDAC) have not been compared in head-to-head trials. Data on optimum treatment sequencing is also lacking. Methods: To assess whether first line (1L) treatment with gemcitabine/nab-paclitaxel (Gem/Nab-P)(SEQ1) or FOLFIRINOX (SEQ2) in the palliative treatment setting impacts survival outcomes, data for patients receiving palliative intent combination chemotherapy between 2016 and May 2020 was extracted from PURPLE, a prospective pancreatic cancer registry enrolling consecutive patients across multiple institutions. Results: Of 637 patients, 180 (28%) who received 1L single agent therapy and/or palliative radiotherapy were excluded. Of the remaining 449 patients, 132 (29%) had locally advanced disease (LA PDAC), 67 had local recurrence (15%), and 250 (56%) had de novo metastatic disease (mPDAC). Patients receiving 1L Gem/Nab-P (n=376, 84%) were older (median 67 vs 59 years, P 〈 0.001), had a higher Charlson Comorbidity Index (CCI) (CCI ≥2: 18% vs 3%, Odds Ratio [OR] 8.0, P=0.002), and poorer performance status (ECOG≥2: 10% vs 1%, OR 8.4, P=0.01) compared to the 1L FOLFIRINOX group (n=73, 16%). 140 (37%) patients receiving 1L Gem/Nab-P (SEQ1) and 32 (44%) patients receiving 1L FOLFIRINOX (SEQ2) received second line (2L) chemotherapy. SEQ1 2L regimens included FOLFIRINOX (n=14), FOLFIRI (n=49), FOLFOX (n=35) and 5FU alone (n=3). SEQ2 2L regimens included Gem/Nab-P (n=19), Gem/5FU (n=4), Gem/Cisplatin (n=1) and gemcitabine alone (n=5). Median progression free survival (mPFS) did not differ between patients receiving 1L Gem/Nab-P vs 1L FOLFIRINOX (5.7 vs 5.1 months, P=0.54); nor did median overall survival (mOS; 11.3 vs 12.3 months, P=0.37). In the subset of patients who went on to receive 2L chemotherapy, mPFS in 2L was shorter for SEQ1 compared to SEQ2 (2.9 vs 5.2 months, Hazard Ratio [HR] 1.3, P=0.03) but mOS did not differ (15.9 vs 17.3 months P=0.91). In the subset with LA PDAC, mPFS in 2L was comparable (2.9 vs 3.3 months, P=0.55) but mOS was significantly longer with SEQ1 (22.5 vs 13.8 months, HR 0.50, P=0.01). In mPDAC, mPFS in 2L was shorter with SEQ1 (2.3 vs 5.6 months, HR 1.64, P=0.03), but mOS did not differ by sequence (13 vs 17 months, P=0.23). Conclusions: There were no significant differences in survival outcomes between 1L choices of chemotherapy, despite patients offered 1L FOLFIRINOX (SEQ2) being younger and fitter. Survival differences observed for LA PDAC versus mPDAC will be further explored. Given the multiple potential confounders, randomised clinical trials are needed to make firmer conclusions regarding the optimal initial treatment for each patient subset.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 19
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 1554-1554
    Abstract: 1554 Background: Colorectal cancer incidence and mortality are increasing among individuals 〈 50 years of age. Data are limited regarding the epidemiology of colorectal adenomas in this younger age group. This study investigated and compared risk factors associated with recurrence of adenomas in individuals under and over 50 years of age. Methods: Pooled analyses from the Wheat Bran Fiber and Ursodeoxycholic Acid phase III, randomized, controlled clinical trials included 1,623 participants, aged 40-80 years. Each completed baseline questionnaires related to family history and lifestyle habits, had one or more colorectal adenomas removed at baseline, and had a follow-up colonoscopy during the trial (mean follow up 36 months). Univariate and multivariate logistic regression modeling estimated the association between age and colorectal adenoma recurrence, and evaluate multiple risk factors, while controlling for confounding factors. Results: A statistically significant increased trend was found for colorectal adenoma recurrence with increasing age ( P trend = 〈 0.001). Multivariate logistic regression revealed that risk factors significantly associated with adenoma recurrence in the ≥50 age group (n = 1,523) included history of previous polyps, characteristics of adenomas removed at baseline (multiple adenomas and villous feature), current smoking, and an increased waist circumference. Although risk profile in the 〈 50 age group (n = 95) shared similarities with that in the ≥50 age group (e.g., current smoking), there were a few notable differences: history of previous polyps was a more prominent predictor for recurrence for the 〈 50 (OR 〈 50 = 4.76 and OR ≥50 = 1.33, P interaction = 0.042), whereas baseline characteristics of adenomas were more important for the ≥50 (multiple adenomas: OR 〈 50 = 0.40 and OR ≥50 = 2.28, P interaction = 0.043). Conclusions: Predisposition to colorectal adenoma is a more important risk factor for recurrence in the 〈 50 as compared to the ≥50. Future studies need to identify susceptibility factors contributing to the increasing incidence of colorectal cancer in this younger age group.
    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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