Oncology

Patients’ and partners’ views of care and treatment provided for metastatic castrate‐resistant prostate cancer in the UK (2019)

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Type of publication:
Journal article

Author(s):
Catt S, Matthews L, May S, Payne H, Mason M, Jenkins V.

Citation:
European Journal of Cancer Care. 2019 Nov;28(6):e13140.

Note:
14 of the 37 participants were recruited from the Royal Shrewsbury Hospital

Abstract:
OBJECTIVE: Documentations of the experiences of patients with advanced prostate cancer and their partners are sparse. Views of care and treatment received for metastatic castrate-resistant prostate cancer (mCRPC) are presented here.
METHODS: Structured interviews conducted within 14 days of a systemic therapy for mCRPC starting and 3 months later explored the following: treatment decisions, information provision, perceived benefits and harms of treatment, and effects of these on patients' and partners' lives.
RESULTS: Thirty-seven patients and 33 partners recruited from UK cancer centres participated. The majority of patients (46%) reported pain was their worst symptom and many wanted to discuss its management (baseline-50%; 3 months-33%). Patients and partners believed treatment would delay progression (>75%), improve wellbeing (33%), alleviate pain (≈12%) and extend life (15% patients, 36% partners). At 3 months, most men (42%) said fatigue was the worst treatment-related side effect (SE), 27% experienced unexpected SEs and 54% needed help with SEs. Most patients received SE information (85% written; 75% verbally); many additionally searched the Internet (33% patients; 55% partners). Only 54% of patients said nurse support was accessible.
CONCLUSION: Pain and other symptom management are not optimal. Increased specialist nurse provision and earlier palliative care links are needed. Dedicated clinics may be justified.

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6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial (2019)

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Type of publication:
Randomised controlled trial

Author(s):
Helena M Earl, Louise Hiller, Anne-Laure Vallier, Shrushma Loi, Karen McAdam, Luke Hughes-Davies, Adrian N Harnett, Mei-Lin Ah-See, Richard Simcock, Daniel Rea, Sanjay Raj, Pamela Woodings, Mark Harries, Donna Howe, Kerry Raynes, Helen B Higgins, Maggie Wilcox, Chris Plummer, Janine Mansi, Ioannis Gounaris, Betania Mahler–Araujo, Elena Provenzano, Anita Chhabra, Jean E Abraham, Carlos Caldas, Peter S Hall, Christopher McCabe, Claire Hulme, David Miles, Andrew M Wardley, David A Cameron, Janet A Dunn on behalf of PERSEPHONE Steering Committee and Trial Investigators.

Randomising consultants at the Royal Shrewsbury Hospital were: *Huzeifa Gadir, *Laura Pettit, *Rajiv Agrawal, and *Sheena Khanduri. Principal investigator at the Royal Shrewsbury Hospital was: *Laura Pettit.

Citation:
Lancet 2019; 393: p. 2599–612

Abstract:
Background: Adjuvant trastuzumab significantly improves outcomes for patients with HER2-positive early breast cancer. The standard treatment duration is 12 months but shorter treatment could provide similar efficacy while reducing toxicities and cost. We aimed to investigate whether 6-month adjuvant trastuzumab treatment is noninferior to the standard 12-month treatment regarding disease-free survival.
Methods: This study is an open-label, randomised phase 3 non-inferiority trial. Patients were recruited from 152 centres in the UK. We randomly assigned patients with HER2-positive early breast cancer, aged 18 years or older, and with a clear indication for chemotherapy, by a computerised minimisation process (1:1), to receive either 6-month or 12-month trastuzumab delivered every 3 weeks intravenously (loading dose of 8 mg/kg followed by maintenance doses of 6 mg/kg) or subcutaneously (600 mg), given in combination with chemotherapy (concurrently or sequentially). The primary endpoint was disease-free survival, analysed by intention to treat, with a non-inferiority margin of 3% for 4-year disease-free survival. Safety was analysed in all patients who received trastuzumab. This trial is registered with EudraCT (number 2006–007018–39), ISRCTN (number 52968807), and ClinicalTrials.gov (number NCT00712140).
Findings: Between Oct 4, 2007, and July 31, 2015, 2045 patients were assigned to 12-month trastuzumab treatment and 2044 to 6-month treatment (one patient was excluded because they were double randomised). Median follow-up was 5·4 years (IQR 3·6–6·7) for both treatment groups, during which a disease-free survival event occurred in 265 (13%) of 2043 patients in the 6-month group and 247 (12%) of 2045 patients in the 12-month group. 4-year disease-free survival was 89·4% (95% CI 87·9–90·7) in the 6-month group and 89·8% (88·3–91·1) in the 12-month group (hazard ratio 1·07 [90% CI 0·93–1·24], non-inferiority p=0·011), showing non-inferiority of the 6-month treatment. 6-month trastuzumab treatment resulted in fewer patients reporting severe adverse events (373 [19%] of 1939 patients vs 459 [24%] of 1894 patients, p=0·0002) or stopping early because of cardiotoxicity (61 [3%] of 1939 patients vs 146 [8%] of 1894 patients, p<0·0001).
Interpretation: We have shown that 6-month trastuzumab treatment is non-inferior to 12-month treatment in patients with HER2-positive early breast cancer, with less cardiotoxicity and fewer severe adverse events. These results support consideration of reduced duration trastuzumab for women at similar risk of recurrence as to those included in the trial.

Link to full-text [open access, no password required]

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Breast Screening Age Extension; High Cancer Pick up Rate of Small Breast Cancers Amenable to Breast and Axillary Conservation (2019)

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Type of publication:
Conference abstract

Author(s):
*Cielecki L. ; *Burley S.; *Lake B.; *Williams S.; *Appleton D.

Citation:
European Journal of Surgical Oncology; Nov 2019; vol. 45 (no. 11); p. 2212-2213

Abstract:
Background: In 2012, Public Health England (PHE) extended the age range for breast screening up to 73. For screening to be an effective tool, one of the Wilson criteria is to detect disease that could be treated at an early stage. This audit aimed to measure the effectiveness of the upper age screening extension in Shropshire by comparing the cancer diagnosis rate to general screening population, size of cancer, and the ability to perform breast conservation.
Method(s): Retrospective analysis of Breast Screening age extension of women invited to be screened aged 71 to 73 years old in Shropshire. Data included number of women invited, uptake rate, recall rate, cancer diagnosis and surgical treatment.
Result(s): 5517 older women were invited into Shropshire Breast Screening Programme as part of the AgeX trial by PHE since September 2014. 4801 women attended and were screened; 87% uptake rate, which exceeds BSP attendance rate of >80%. 104 women were recalled to assessment (2.1%) which is below BSP standard of <5% recall rate for incident screens. 46.1% (48) of women recalled to assessment were given a cancer diagnosis, this is compared to 30.5% in general screening population. 41.6% of the invasive cancer was <15mm. 95.8% of patients had surgery, with 70.8% of patients having breast and axillary conservation surgery.
Conclusion(s): BSP Standards uptake rate and recall rate have been exceeded by upper age extension. Our experience shows high cancer pick up rate of small cancers with the majority patients able to have breast conserving surgery.

Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial (2019)

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Type of publication:
Journal article

Author(s):
Clarke, N W; Ali, A; Ingleby, F C; Hoyle, A; Amos, C L; Attard, G; Brawley, C D; Calvert, J; Chowdhury, S; Cook, A; Cross, W; Dearnaley, D P; Douis, H; Gilbert, D; Gillessen, S; Jones, R J; Langley, R E; MacNair, A; Malik, Z; Mason, M D; Matheson, D; Millman, R; Parker, C C; Ritchie, A W S; Rush, H; Russell, J M; Brown, J; Beesley, S; Birtle, A; Capaldi, L; Gale, J; Gibbs, S; Lydon, A; Nikapota, A; Omlin, A; O'Sullivan, J M; Parikh, O; Protheroe, A; Rudman, S; *Srihari, N N; Simms, M; Tanguay, J S; Tolan, S; Wagstaff, J; Wallace, J; Wylie, J; Zarkar, A; Sydes, M R; Parmar, M K B; James, N D

Citation:
Annals of Oncology; Dec 2019 30(12) p. 1992-2003

Abstract:
BACKGROUND STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients.
METHODS We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional.
RESULTS Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69-0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57-0.76, P < 0.001) and progression-free survival (HR = 0.69, 95% CI 0.59-0.81, P < 0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P > 0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression).
CONCLUSIONS The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.

Link to full-text [open access - no password required]

See Erratum - The authors regret that Fig.2F has been incorrectly titled. The correct title is “Failure-free survival high burden M1”.

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Best supportive care (BSC) with or without lowdose chemotherapy (chemo) in frail elderly patients with advanced gastroesophageal cancer (aGOAC): The uncertain randomization of the GO2 phase III trial (2019)

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Type of publication:
Conference abstract

Author(s):
Swinson D.; Hingorani M.; Stokes Z.; Dent J.; Guptal K.; *Chatterjee A.; Kamposioras K.; Grumett S.A.; Khan M.; Marshall H.; Ruddock S.; Allmark C.; Katona E.; Howard H.C.; Velikova G.; Lord S.; Hall P.S.; Seymour M.T.

Citation:
Journal of Clinical Oncology; May 2019; vol. 37

Abstract:
Background: Before 2000, trials comparing BSC +/chemo for aGOAC showed overall survival (OS) benefit, but in predominantly fit patients (pts). We have revisited this question in a modern context, using lowdose chemo in a frail population, with comprehensive baseline health and frailty assessment.
Method(s): In the GO2 trial, elderly and/or frail aGOAC pts with a ?certain? indication for chemo were randomised between 3 chemo doses. In this GO2 sub-study, pts with an ?uncertain? indication for chemo were instead randomised to BSC +/- the lowest dose chemo. Pts were eligible if clinician and pt agreed the indication for chemo was uncertain. There was no PS threshold, but eGFR >=30 and bili < 2xULN were required. Baseline assessment included global QL, symptom & functional scales, frailty and comorbidity. Randomisation was 1:1 to BSC alone, or with oxaliplatin 78 mg/m2 d1, capecitabine 375 mg/m2 bd d121 (modified if eGFR 3050 ml/min or bili 1.52.0 xULN), q21d. QL was reassessed after 9 and 18 wks. The primary endpoint analysis was OS, adjusted for baseline factors. The sample size for this exploratory sub-study was not preset, but around 60 pts were anticipated.
Result(s): 558 pts entered GO2 at 61 centres 201417, of whom only 45 pts (8%) at 21 centres entered this uncertain randomisation. This would provide 80% power at p = 0.05 (2tailed) to detect an OS HR of 0.3. OS was shorter in pts with worse baseline PS (p<0.01) or distant mets (p<0.05). OS was not significantly improved with chemo; however we cannot exclude HR >0.32. QL deteriorated less with BSC+chemo than with BSC alone.
Conclusion(s): In this frail, poor PS population, we observed a small survival benefit with chemo but this did not reach statistical significance. Clinicians should carefully consider BSC alone as a valid treatment option for aGOAC pts with poor PS and/or frailty.

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Addition of Docetaxel to First-line Long-term Hormone Therapy in Prostate Cancer (STAMPEDE): Modelling to Estimate Long-term Survival, Quality-adjusted Survival, and Cost-effectiveness (2018)

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Type of publication:
Journal article

Author(s):
Woods B.S.; Sideris E.; Sculpher M.J.; Sydes M.R.; Gannon M.R.; Parmar M.K.B.; Millman R.; Alzouebi M.; Attard G.; Dearnaley D.P.; Birtle A.J.; Brock S.; Cathomas R.; Chakraborti P.R.; Cook A.; Cross W.R.; Gale J.; Gibbs S.; Graham J.D.; Hughes R.; Jones R.J.; Laing R.; Mason M.D.; Matheson D.; McLaren D.B.; O'Sullivan J.M.; Parikh O.; Parker C.C.; Peedell C.; Protheroe A.; Ritchie A.W.S.; Robinson A.; Russell J.M.; Simms M.S.; *Srihari N.N.; Srinivasan R.; Staffurth J.N.; Sundar S.; Thalmann G.N.; Tolan S.; Tran A.T.H.; Tsang D.; Wagstaff J.; James N.D.

Citation:
European Urology Oncology; Dec 2018; vol. 1 (no. 6); p. 449-458

Abstract:
BACKGROUND: Results from large randomised controlled trials have shown that adding docetaxel to the
standard of care (SOC) for men initiating hormone therapy for prostate cancer (PC) prolongs survival for those with metastatic disease and prolongs failure-free survival for those without. To date there has been no formal assessment of whether funding docetaxel in this setting represents an appropriate use of UK National Health Service (NHS) resources.
OBJECTIVE(S): To assess whether administering docetaxel to men with PC starting long-term hormone therapy is cost-effective in a UK setting.
DESIGN, SETTING, AND PARTICIPANTS: We modelled health outcomes and costs in the UK NHS using data collected within the STAMPEDE trial, which enrolled men with high-risk, locally advanced metastatic or recurrent PC starting first-line hormone therapy. INTERVENTION: SOC was hormone therapy for >=2 yr and radiotherapy in some patients. Docetaxel (75mg/m2) was administered alongside SOC for six three-weekly cycles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The model generated lifetime predictions of costs, changes in survival duration, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS AND LIMITATIONS: The model predicted that docetaxel would extend survival (discounted quality-adjusted survival) by 0.89 yr (0.51) for metastatic PC and 0.78 yr (0.39) for nonmetastatic PC, and would be cost-effective in metastatic PC (ICER 5514/QALY vs SOC) and nonmetastatic PC (higher QALYs, lower costs vs SOC). Docetaxel remained cost-effective in nonmetastatic PC when the assumption of no survival advantage was modelled.
CONCLUSION(S): Docetaxel is cost-effective among patients with nonmetastatic and metastatic PC in a UK setting. Clinicians should consider whether the evidence is now sufficiently compelling to support docetaxel use in patients with nonmetastatic PC, as the opportunity to offer docetaxel at hormone therapy initiation will be missed for some patients by the time more mature survival data are available. PATIENT SUMMARY: Starting docetaxel chemotherapy alongside hormone therapy represents a good use of UK National Health Service resources for patients with prostate cancer that is high risk or has spread to other parts of the body.

Local experience at DGH shows combination Pertuzumab and Herceptin nearly doubles PCR rate of Neo-adjuvant Chemotherapy (NAC) in HER2 positive breast cancer (2018)

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Type of publication:
Poster presentation

Author(s):
*Blossom Lake, *Donna Appleton, *Abel Zachariah, *Habib Khan, *Kerry Flemming, *Jennifer Neill, *Laura Pettit

Citation:
Presented at BASO: The Association for Cancer Surgery

Link to poster [PDF]

Breast Reconstruction Affects Coping Mechanisms in Breast Cancer Survivors (2019)

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Type of publication:
Journal article

Author(s):
*Lake, Blossom; Fuller, Heidi R; *Rastall, Sarah; *Usman, Tamoor

Citation:
Indian Journal of Surgery; Feb 2019; vol. 81 (no. 1); p. 43-50

Abstract:
Coping strategies used by women with breast cancer are vital for adjustment to their disease. Whilst it is clear that factors such as age at diagnosis, social support and ethnicity can influence coping mechanisms, there is currently no information about whether breast reconstruction changes mechanisms of coping for such patients. The aims of this study, therefore, were to determine how women who have had immediate breast reconstruction and mastectomy cope, compared to those who have mastectomy alone, and whether there are differences in coping mechanisms due to breast reconstruction surgery. This was a retrospective cohort study, using a standardised questionnaire called the Brief Cope Scale. Inclusion criteria was the following: all women
who had immediate breast reconstruction and mastectomy in Shropshire from 2003 to 2014 for ductal carcinoma in situ or node-negative invasive breast cancer. Each patient was matched for year of diagnosis, adjuvant therapy and age to one woman who had mastectomy alone. Two hundred thirty-four questionnaires were sent with a 58% response rate. Significantly more patients from the reconstruction cohort coped by active coping (T value 1.66, P value 0.04) compared to those in the mastectomy alone cohort. In contrast, significantly more patients in the mastectomy alone cohort coped by active venting compared to the reconstruction cohort (T value 1.71, P value 0.04). This study indicates for the first time that breast reconstruction may alter coping mechanisms in breast cancer survivors. Awareness of these coping mechanisms will enable clinicians to provide appropriate, individualised support.