3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial (2018)

Type of publication:
Randomised controlled trial

Author(s):
Iveson TJ, Kerr RS, Saunders MP, Cassidy J, Hollander NH, Tabernero J, Haydon A, Glimelius B, Harkin A, Allan K, McQueen J, Scudder C, Boyd KA, Briggs A, Waterston A, Medley L, Wilson C, Ellis R, Essapen S, Dhadda AS, Harrison M, Falk S, Raouf S, Rees C, Olesen RK, Propper D, Bridgewater J, Azzabi A, Farrugia D, Webb A, Cunningham D, Hickish T, Weaver A, Gollins S, Wasan HS, Paul J. [SaTH was one of the sites this trial took place at]

Citation:
Lancet Oncology 2018 Apr;19(4):562-578

Abstract:
BACKGROUND: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment.
METHODS: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing.
FINDINGS: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1-78·2) for the 3 month group and 77·1% (75·6-78·6) for the 6 month group, giving a hazard ratio of 1·006 (0·909-1·114, test for non-inferiority p=0·012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group).
INTERPRETATION: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care.
FUNDING: Medical Research Council, Swedish Cancer Society, NETSCC, and Cancer Research UK.

Link to full-text [Open access – no password required]

An audit of ‘real world’ systemic chemotherapy in breast cancer patients over the age of 70 in one U.K. Cancer Centre (2018)

Type of publication:
Conference abstract

Author(s):
*Choudhary Y.; *Pettit L.; *Khanduri S.

Citation:
European Journal of Surgical Oncology; Mar 2018; vol. 44

Abstract:
Background: Breast cancer incidence among the over 70’s is increasing. Trial data from this age group is not as extensive when compared with younger patients. Co-morbidities are common and may lead to poor tolerance of chemotherapy. Cytotoxic chemotherapy usage in patients over 70 was audited to record toxicity and tolerability.Method: Patients aged >70 years, diagnosed with invasive breast cancer between 01/01/2015 and 31/12/2015 treated with cytotoxic chemotherapy at the Shrewsbury and Telford Hospital NHS Trust were identified from the Somerset database. Clinical information was obtained from an electronic portal. Data collected: demographics, performance status, tumour characteristics, ER/PR and HER2 status, chemotherapy regimen, treatment intent, number of chemotherapy cycles planned, number given, toxicities, and hospital admissions. Data was collected on an excel database.Results: Thirty patients were identified, all female. 26 were between 71 and 75, 2 were between 76 and 80, 2 > 80 years. 20 patients (67%) ER/PR receptor positive. 15 (50%) HER2 positive. The majority 29 (97%) had a performance status of 0/1. Cardiovascular co-morbidities were the most common (57% pre-existing cardiovascular disease). 25 (83%) were treated with adjuvant intent. 15 (50%) were admitted to hospital, 6 (20%) with neutropenic sepsis. 12 (40%) had dose reductions. 21 (70%) completed their planned number of cycles. Chemotherapy was discontinued in 7 (23%) due to toxicity and 1 patient remains on treatment at the time of this audit. There were no patient deaths within 30 days of commencing chemotherapy.Conclusion: Chemotherapy usage in the >70’s was associated with higher risk breast cancer. Despite good baseline performance status, 50% of patients required hospital admission and 27% discontinued treatment due to toxicity. The decision to use chemotherapy must also account for potential toxicities and impact on quality of life. Increased contact with health professionals including tele-consults and increased specialist nurse support, will help to predict and manage toxicity and reduce admissions.

Group pre-assessment for patients undergoing chemotherapy: Our experience at The Royal Shrewsbury Hospital (2017)

Type of publication:
Conference abstract

Author(s):
*Allos B.; *Redgrave R.; *Davies W.; *Chatterjee A.

Citation:
Lung Cancer; Jan 2017; vol. 103, Supplement 1, Page S47

Abstract:
Introduction: Waiting time targets in England and Wales state cancer treatment must commence within 31 days of the treatment plan being agreed. Often, pressures on chemotherapy units, such as low staffing levels and capacity, delays starting chemotherapy. This may impact outcomes. To improve capacity and waiting times we have implemented group pre-assessment (GPAC) for all prospective chemotherapy patients at our trust. Methods: Previously each patient received a 1-hour pre-assessment appointment with a dedicated nurse. For non-urgent patients we have established GPAC clinics since January 2014. These are run three times a week by volunteers in conjunction with one chemotherapy nurse and accommodate 6 patients per session. Patients watch a 25-minute DVD providing general information on chemotherapy in addition to introducing the unit, nurses and general treatment procedures. A unit tour follows this. Each patient receives a diagnosis-specific  tumour pack and the session concludes with a 10-minute one-to-one meeting with a nurse to discuss their personal treatment regime. Results: We pre-assess up to 18 patients a week via GPAC. Since implementation we have reduced nursing hours needed for this service to a maximum of 6 hours per week. From September 2015 to August 2016 a total of 667 patients attended GPAC clinic with 312 nursing hours required. Our unit has consequently saved 355 nursing hours over that time period (Figure 1). Patient satisfaction with the service remains high with 24/25 (96%) of patients surveyed rating the service as good to excellent across five categories. With GPAC initiation, our average chemotherapy waiting time has reduced to 13 days from over 20 days. Conclusion: By initiating GPAC our department has significantly saved nursing hours allowing us to reallocate these to chemotherapy delivery and service development. With increased capacity to treat patients waiting times have been significantly reduced. This has not been to the detriment of patient satisfaction. (Table Presented).

Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial (2017)

Type of publication:
Randomised controlled trial

Author(s):
Earl, Helena M; Hiller, Louise; Howard, Helen C; Dunn, Janet A; Young, Jennie; Bowden, Sarah J; McDermaid, Michelle; Waterhouse, Anna K; Wilson, Gregory; *Agrawal, Rajiv; O’Reilly, Susan; Bowman, Angela; Ritchie, Diana M; Goodman, Andrew; Hickish, Tamas; McAdam, Karen; Cameron, David; Dodwell, David; Rea, Daniel W; Caldas, Carlos; Provenzano, Elena; Abraham, Jean E; Canney, Peter; Crown, John P; Kennedy, M John; Coleman, Robert; Leonard, Robert C; Carmichael, James A; Wardley, Andrew M; Poole, Christopher J; tAnGo trial collaborators

Citation:
The Lancet. Oncology, Volume 18, No. 6, p755–769, June 2017

Abstract:
BACKGROUND The tAnGo trial was designed to investigate the potential role of gemcitabine when added to anthracycline and taxane-containing adjuvant chemotherapy for early breast cancer. When this study was developed, gemcitabine had shown significant activity in metastatic breast cancer, and there was evidence of a favourable interaction with paclitaxel. METHOD StAnGo was an international, open-label, randomised, phase 3 superiority trial that enrolled women aged 18 years or older with newly diagnosed, early-stage breast cancer who had a definite indication for chemotherapy, any nodal status, any hormone receptor status, Eastern Cooperative Oncology Group performance status of 0-1, and adequate bone marrow, hepatic, and renal function. Women were recruited from 127 clinical centres and hospitals in the UK and Ireland, and randomly assigned (1:1) to one of two treatment regimens: epirubicin, cyclophosphamide, and paclitaxel (four cycles of 90 mg/m2 intravenously administered epirubicin and 600 mg/m2 intravenously administered cyclophosphamide on day 1 every 3 weeks, followed by four cycles of 175 mg/m2 paclitaxel as a 3 h infusion on day 1 every 3 weeks) or epirubicin, cyclophosphamide, and paclitaxel plus gemcitabine (the same chemotherapy regimen as
the other group, with the addition of 1250 mg/m2 gemcitabine to the paclitaxel cycles, administered intravenously as a 0·5 h infusion on days 1 and 8 every 3 weeks). Patients were randomly assigned by a central computerised deterministic minimisation procedure, with stratification by country, age, radiotherapy intent, nodal status, and oestrogen receptor and HER-2 status. The primary endpoint was disease-free survival and the trial aimed to detect 5% differences in 5-year disease-free survival between the treatment groups. Recruitment completed in 2004 and this is the final, intention-to-treat analysis. This trial is registered with EudraCT (2004-002927-41), ISRCTN (51146252), and ClinicalTrials.gov (NCT00039546).FINDINGS Between Aug 22, 2001, and Nov 26, 2004, 3152 patients were enrolled and randomly assigned to epirubicin, cyclophosphamide, paclitaxel, and gemcitabine (gemcitabine group; n=1576) or to epirubicin, cyclophosphamide, and paclitaxel (control group; n=1576). 11 patients (six in the gemcitabine group and five in the control group) were ineligible because of pre-existing metastases and were therefore excluded from the analysis. At this protocol-specified final analysis (median follow-up 10 years [IQR 10-10]), 1087 disease-free survival events and 914 deaths had occurred. Disease-free survival did not differ significantly between the treatment groups at 10 years (65% [63-68] in the gemcitabine group vs 65% [62-67] in the control group), and median disease-free survival was not reached (adjusted hazard ratio 0·97 [95% CI 0·86-1·10], p=0·64). Toxicity, dose intensity, and a detailed safety substudy showed both regimens to be safe, deliverable, and tolerable. Grade 3 and 4 toxicities were reported at expected levels in both groups. The most common were neutropenia (527 [34%] of 1565 patients in the gemcitabine group vs 412 [26%] of 1567 in the control group), myalgia and arthralgia (207 [13%] vs 186 [12%]), fatigue (207 [13%] vs 152 [10%]), infection (202 [13%] vs 141 [9%]), vomiting (143 [9%] vs 108 [7%]), and nausea (132 [8%] vs 102 [7%]).INTERPRETATION The addition of gemcitabine to anthracycline and taxanebased adjuvant chemotherapy at this dose and schedule confers no therapeutic advantage in terms of disease free survival in early breast cancer, although it can cause increased toxicity. Therefore, gemcitabine has not been added to standard adjuvant chemotherapy in breast cancer for any subgroup.FUNDING Cancer Research UK core funding for Clinical Trials Unit at the University of Birmingham, Eli Lilly, Bristol-Myers Squibb, and Pfizer.

Altmetric Attention Score

Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multicentre, double-blind, placebo-controlled randomised trial (2014)

Type of publication:
Randomised Controlled Trial

Author(s):
Dutton SJ,Ferry DR,Blazeby JM,Abbas H,Dahle-Smith A,Mansoor W,Thompson J,Harrison M,*Chatterjee A,Falk S,Garcia-Alonso A,Fyfe DW,Hubner RA,Gamble T,Peachey L,Davoudianfar M,Pearson SR,Julier P,Jankowski J,Kerr R,Petty RD

Citation:
Lancet Oncology, 07 2014, vol./is. 15/8(894-904), 1470-2045;1474-5488 (2014 Jul)

Abstract:
BACKGROUND: Evidence is scarce for the effectiveness of therapies for oesophageal cancer progressing after chemotherapy, and no randomised trials have been reported. We aimed to compare gefitinib with placebo in previously treated advanced oesophageal cancer.METHODS: For this phase 3, parallel, randomised, placebo-controlled trial, eligible patients were adults with advanced oesophageal cancer or type I/II Siewert junctional tumours, histologically confirmed squamous-cell carcinoma or adenocarcinoma, who had progressed after chemotherapy, with WHO performance status 0-2, and with measurable or evaluable disease on CT scan. Participants were recruited from 48 UK centres and randomly assigned (1:1) to gefitinib (500 mg) or matching placebo by simple randomisation with no stratification factors. Patients, clinicians, and trial office staff were masked to treatment allocation. Treatment continued until disease progression, unacceptable toxicity, or patient choice. The primary outcome was overall survival, analysed by intention to treat. This trial is registered, number ISRCTN29580179.FINDINGS: Between March 30, 2009, and Nov 18, 2011, 450 patients were randomly assigned to treatment groups (one patient withdrew consent; 224 patients allocated gefitinib and 225 allocated placebo included in analyses). Overall survival did not differ between groups (median 373 months, 95% CI 323-450, for gefitinib vs 367 months, 95% CI 297-437, for placebo; hazard ratio 090, 95% CI 074-109, p=029). Among the prespecified patient-reported outcomes (110 patients on gefitinib and 121 on placebo completed both baseline and 4 week questionnaires and were included in analyses), odynophagia was significantly better in the gefitinib group (adjusted mean difference -861, 95% CI -1449 to -273; n=227; p=0004), whereas the other outcomes were not significantly improved compared with placebo: global quality of life (269, 95% CI -233 to 772, n=231, p=0293), dysphagia (-318, 95% CI -836 to 200, n=231, p=0228), and eating (-411, 95% CI -996 to 175, n=229, p=0168). Median progression-free survival was marginally longer with gefitinib than it was with placebo (157 months, 95% CI 123-190 in the gefitinib group vs 117 months, 95% CI 107-137 in the placebo group; HR 080, 95% CI 066-096, p=0020). The most common toxicities were diarrhoea (36 [16%] of 224 patients on gefitinib vs six [3%] of 225 on placebo) and skin toxicity (46 [21%] vs two [1%]), both mostly grade 2. The commonest grade 3-4 toxicities were fatigue (24 [11%] vs 13 [6%] patients) and diarrhoea (13 [6%] vs two [1%]). Serious adverse events were reported in 109 (49%) of 224 patients assigned to gefitinib and 101 (45%) of 225 on placebo. 54 (24%) of patients in the gefitinib group achieved disease control at 8 weeks, as did 35 (16%) of patients on placebo (p=0023).INTERPRETATION: The use of gefitinib as a second-line treatment in oesophageal cancer in unselected patients does not improve overall survival, but has palliative benefits in a subgroup of these difficult-to-treat patients with short life expectancy. Future research should focus on identification of predictive biomarkers to identify this subgroup of benefiting patients.FUNDING: Cancer Research UK. Copyright 2014 Elsevier Ltd. All rights reserved.

Link to more details or full-text: http://www.sciencedirect.com/science/article/pii/S1470204514700245