A systematic review of outcomes after salvage abdominoperineal resection for persistent or recurrent anal squamous cell cancer.

AIM: Up to 30% of patients with squamous cell cancer of the anus (SCCA) will require a salvage abdominoperineal resection (APR) for either persistent or recurrent disease. The objective of this study was to assess cancer-related outcomes in patients with (i) persistent or (ii) recurrent SCCA. METHOD: Embase and MEDLINE were searched. Publications were included if they assessed overall survival (OS), disease-free survival (DFS) and locoregional recurrence or metastatic disease after salvage APR for persistent or recurrent SCCA. RESULTS: A total of 28 retrospective case series (study size ranged from nine to 111) met our inclusion criteria. The median time to salvage APR was 2.6 months [interquartile range (IQR) 2.6-5.0 months, six studies] for persistent disease and 27.6 months (IQR 15.0-32.7 months, five studies) for recurrent disease. The median 5-year OS from the time of salvage APR was 45.0% (IQR 32.0%-52.3%, 10 studies) for persistent disease and 51.0% (IQR 36.0%-60.9%, 11 studies) for recurrent disease. The median 5-year DFS following salvage APR was 44.0% (IQR 29.5%-53.0%, 10 studies) for all patients. Following salvage APR, the median locoregional recurrence rate was 23.5% (IQR 15.8%- 46.9%, 19 studies) and 9.0% (IQR 6.4%-13.3%, 16 studies) of patients developed metastatic disease after salvage APR. CONCLUSION: Our review characterizes the best evidence for outcomes following salvage APR for patients with persistent or recurrent SCCA. The evidence is limited by the quality of included studies, as many were single centre case series.

Do Contemporary Randomized Controlled Trials Meet ESMO Thresholds for Meaningful Clinical Benefit?

Background: The European Society for Medical Oncology (ESMO) recently released a magnitude of clinical benefit scale (ESMO-MCBS) for systemic therapies for solid cancers. Here, we evaluate contemporary randomized controlled trials (RCTs) against the proposed ESMO thresholds for meaningful clinical benefit. Methods: RCTs evaluating systemic therapy for breast cancer, nonsmall cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic cancer published 2011-2015 were reviewed. Data were abstracted regarding trial characteristics and outcomes, and these were applied to the ESMO-MCBS. We also determined whether RCTs were designed to detect an effect that would meet clinical benefit as defined by the ESMO-MCBS. Results: About 277 eligible RCTs were included (40% breast, 31% NSCLC, 22% CRC, 6% pancreas). Median sample size was 532 and 83% were funded by industry. Among all 277 RCTs, the experimental therapy was statistically superior to the control arm in 138 (50%) trials: results of only 31% (43/138) of these trials met the ESMO-MCBS clinical benefit threshold. RCTs with curative intent were more likely to meet clinically meaningful thresholds than those with palliative intent [61% (19/31) versus 22% (24/107), P < 0.001]. Among the 226 RCTs for which the ESMO-MCBS could be applied, 31% (70/226) were designed to detect an effect size that could meet ESMO-MCBS thresholds. Conclusion: Less than one-third of contemporary RCTs with statistically significant results meet ESMO thresholds for meaningful clinical benefit, and this represents only 15% of all published trials. Investigators, funding agencies, regulatory agencies, and industry should adopt more stringent thresholds for meaningful benefit in the design of future RCTs.

Population-based study to re-evaluate optimal lymph node yield in colonic cancer.

BACKGROUND: It is well established that lymph node (LN) yield in colonic cancer resection has prognostic significance, although optimal numbers are not clear. Here, LN thresholds associated with both LN positivity and survival were evaluated in a single population-based data set. METHODS: Treatment records were linked to the Ontario Cancer Registry to identify a 25 per cent random sample of all patients with stage II/III colonic cancer between 2002 and 2008. Multivariable regression and Cox models evaluated factors associated with LN positivity and cancer-specific survival (CSS) respectively. Optimal thresholds were obtained using sequential regression analysis. RESULTS: On adjusted analysis of 5508 eligible patients, younger age (P < 0·001), left-sided tumours (P = 0·003), higher T category (P < 0·001) and greater LN yield (relative risk 0·89, 95 per cent c.i. 0·81 to 0·97; P = 0·007) were associated with a greater likelihood of LN positivity. Regression analyses with multiple thresholds suggested no substantial increase in LN positivity beyond 12-14 LNs. Cox analysis of stage II disease showed that lower LN yield was associated with a significant increase in the risk of death from cancer (CSS hazard ratio range 1·55-1·74; P < 0·001) compared with a greater LN yield, with no significant survival benefit beyond a yield of 20 LNs. Similarly, for stage III disease, a lower LN yield was associated with an increase in the risk of death from cancer (CSS hazard ratio range 1·49-2·20; P < 0·001) versus a large LN yield. In stage III disease, there was no observed LN threshold for survival benefit in the data set. CONCLUSION: There is incongruity in the optimal LN evaluation for colonic cancer. Although the historically stated threshold of 12 LNs may ensure accurate staging in colonic cancer, thresholds for optimal survival are associated with far greater yields.

Is there a sex effect in colon cancer? Disease characteristics, management, and outcomes in routine clinical practice.

INTRODUCTION: The incidence of colon cancer varies by sex. Whether women and men show differences in extent of disease, treatment, and outcomes is not well described. We used a large population-based cohort to evaluate sex differences in colon cancer. METHODS: Using the Ontario Cancer Registry, all cases of colon cancer treated with surgery in Ontario during 2002-2008 were identified. Electronic records of treatment identified use of surgery and adjuvant chemotherapy. Pathology reports for a random 25% sample of all cases were obtained, and disease characteristics, treatment, and outcomes in women and men were compared. A Cox proportional hazards model was used to identify factors associated with overall (os) and cancer-specific survival (css). RESULTS: The study population included 7249 patients who underwent resection of colon cancer; 49% (n = 3556) were women. Stage of disease and histologic grade did not vary by sex. Compared with men, women were more likely to have right-sided disease (55% vs. 44%, p ≤ 0.001). Surgical procedure and lymph node yield did not differ by sex. Adjuvant chemotherapy was delivered to 18% of patients with stage ii and 64% of patients with stage iii disease; when adjusted for patient- and disease-related factors, use of adjuvant chemotherapy was similar for women and men [relative risk: 0.99; 95% confidence interval (ci): 0.94 to 1.03]. Adjusted analyses demonstrated that os [hazard ratio (hr): 0.80; 95% ci: 0.75 to 0.86] and css (hr: 0.82; 95% ci: 0.76 to 0.90) were superior for women compared with men. CONCLUSIONS: Long-term survival after colon cancer is significantly better for women than for men, which is not explained by any substantial differences in extent of disease or treatment delivered.

Lymph node evaluation for colon cancer in routine clinical practice: a population-based study.

BACKGROUND: Guidelines recommend that 12 or more lymph nodes (lns) be evaluated during surgical resection of colon cancer. Here, we report ln yield and its association with survival in routine practice. METHODS: Electronic records of treatment were linked to the population-based Ontario Cancer Registry to identify all patients with colon cancer treated during 2002-2008. The study population (n = 5508) included a 25% random sample of patients with stage ii or iii disease. Modified Poisson regression was used to identify factors associated with ln yield; Cox models were used to explore the association between ln yield and overall (os) and cancer-specific survival (css). RESULTS: During 2002-2008, median ln yield increased to 17 from 11 nodes (p < 0.001), and the proportion of patients with 12 or more nodes evaluated increased to 86% from 45% (p < 0.001). Lymph node positivity did not change over time (to 53% from 54%, p = 0.357). Greater ln yield was associated with younger age (p < 0.001), less comorbidity (p = 0.004), higher socioeconomic status (p = 0.001), right-sided tumours (p < 0.001), and higher hospital volume (p < 0.001). In adjusted analyses, a ln yield of less than 12 nodes was associated with inferior os and css for stages ii and iii disease [stage ii os hazard ratio (hr): 1.36; 95% confidence interval (ci): 1.19 to 1.56; stage ii css hr: 1.52; 95% ci: 1.26 to 1.83; and stage iii os hr: 1.45; 95% ci: 1.30 to 1.61; stage iii css hr: 1.54; 95% ci: 1.36 to 1.75]. CONCLUSIONS: Despite a temporal increase in ln yield, the proportion of cases with ln positivity has not changed. Lymph node yield is associated with survival in patients with stages ii and iii colon cancer. The association between ln yield and survival is unlikely to be a result of stage migration.

Toward improved goals-of-care documentation in advanced cancer: report on the development of a quality improvement initiative.

BACKGROUND: Documentation of advance care planning for patients with terminal cancer is known to be poor. Here, we describe a quality improvement initiative. METHODS: Patients receiving palliative chemotherapy for metastatic lung, pancreatic, colorectal, and breast cancer during 2010-2015 at the Cancer Centre of Southeastern Ontario were identified from electronic pharmacy records. Clinical notes were reviewed to identify documentation of care plans in the event of acute deterioration. After establishing baseline practice, we sought to improve documentation of goals of care and referral rates to palliative care. Using quality improvement methodology, we developed a guideline, a standardized documentation system, and a process to facilitate early referral to palliative care. RESULTS: During 2010-2015, 456 patients were included in the baseline cohort: 63% with lung cancer, 16% with colorectal cancer, 13% with pancreatic cancer, and 7% with breast cancer. Care goals in the event of an acute illness were documented by medical oncologists in 6% of cases (26 of 456). Of the 456 patients, 47% (n = 214) were seen by palliative care; care goals were documented by palliative care in 48% of the patients seen (103 of 214). With those baseline data in hand, a local practice guideline and process was developed to facilitate the identification of patients for whom advance care planning and early palliative care referral should be considered. A system was also established so that goals-of-care documentation will be supported with a written framework and broadly accessible in the electronic medical record. CONCLUSIONS: Low rates of documentation of advance care planning and referral to palliative care persist and have stimulated a local quality improvement initiative.

Mental health services use by melanoma patients receiving adjuvant interferon: association of pre-treatment mental health care with early discontinuation.

BACKGROUND: Although high-dose interferon (hd-ifn) is the sole approved adjuvant systemic treatment for melanoma in many jurisdictions, it is toxic. We sought to assess the population-level effects of hd-ifn toxicity, particularly neuropsychiatric toxicity, hypothesizing that such toxicity would have the greatest effect on mental health services use in advanced resected melanoma. METHODS: This retrospective population-based registry study considered all melanoma patients receiving adjuvant hd-ifn in Ontario during 2008-2012. Toxicity was investigated through health services use compatible with hd-ifn toxicity (for example, mental health physician billings). Using stage data reported from cancer centres about a subset of patients (stages iib-iiic), a propensity-matched analysis compared such service use in patients who did and did not receive hd-ifn. Associations between early hd-ifn discontinuation and health services use were examined. RESULTS: Of 718 melanoma patients who received hd-ifn, 12% were 65 years of age and older, and 83% had few or no comorbidities. One third of the patients experienced 1 or more toxicity-associated health care utilization events within 1 year of starting hd-ifn. Of 420 utilization events, 364 (87%) were mental health-related, with 54% being family practitioner visits, and 39% being psychiatrist visits. In the propensity-matched analysis, patients receiving hd-ifn were more likely than untreated matched controls to use a mental health service (p = 0.01), with 42% of the control group and 51% of the hd-ifn group using a mental health service in the period spanning the 12 months before to the 24 months after diagnosis. In the multivariable analysis, early drug discontinuation was more likely in the presence of pre-existing mental health issues (odds ratio: 2.0; 95% confidence limits: 1.1, 3.4). CONCLUSIONS: Stage iib-iiic melanoma patients carry a substantial burden of mental health services use whether or not receiving hd-ifn, highlighting an important survivorship issue for these patients. High-dose interferon is associated with more use of mental health services, and pre-treatment use of mental health services is associated with treatment discontinuation. That association should be kept in mind when hd-ifn is being considered.

Research output and the public health burden of cancer: is there any relationship?

PURPOSE: The relative distribution of research output across cancer sites is not well described. Here, we evaluate whether the volume of published research is proportional to the public health burden of individual cancers. We also explore whether research output is proportional to research funding. METHODS: Statistics from the Canadian and American cancer societies were used to identify the top ten causes of cancer death in 2013. All journal articles and clinical trials published in 2013 by Canadian or U.S. authors for those cancers were identified. Total research funding in Canada by cancer site was obtained from the Canadian Cancer Research Alliance. Descriptive statistics and Pearson correlation coefficients were used to describe the relationship between research output, cancer mortality, and research funding. RESULTS: We identified 19,361 publications and 2661 clinical trials. The proportion of publications and clinical trials was substantially lower than the proportion of deaths for lung (41% deaths, 15% publications, 16% clinical trials), colorectal (14%, 7%, 6%), pancreatic (10%, 7%, 5%), and gastroesophageal (7%, 5%, 3%) cancers. Conversely, research output was substantially greater than the proportion of deaths for breast cancer (10% deaths, 29% publications, 30% clinical trials) and prostate cancer (8%, 15%, 17%). We observed a stronger correlation between research output and funding (publications r = 0.894, p < 0.001; clinical trials r = 0.923, p < 0.001) than between research output and cancer mortality (r = 0.363, p = 0.303; r = 0.340, p = 0.337). CONCLUSIONS: Research output is not well correlated with the public health burden of individual cancers, but is correlated with the relative level of research funding.

Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.

Comparing effectiveness with efficacy: outcomes of palliative chemotherapy for non-small-cell lung cancer in routine practice.

INTRODUCTION: Randomized controlled trials (rcts) are the "gold standard" for establishing treatment efficacy; however, efficacy does not automatically translate to a comparable level of effectiveness in routine practice. Our objectives were to □ describe outcomes of palliative platinum-doublet chemotherapy (ppdc) in non-small-cell lung cancer (nsclc) in routine practice, in terms of survival and well-being; and□ compare the effectiveness of ppdc in routine practice with its efficacy in rcts. METHODS: Electronic treatment records were linked to the Ontario Cancer Registry to identify patients who underwent ppdc for nsclc at Ontario's regional cancer centres between April 2008 and December 2011. At each visit to the cancer centre, a patient's symptoms are recorded using the Edmonton Symptom Assessment System (esas). Score on the esas "well-being" item was used here as a proxy for quality of life (qol). Survival in the cohort was compared with survival in rcts, adjusting for differences in case mix. Changes in the esas score were measured 2 months after treatment start. The proportion of patients having improved or stable well-being was compared with the proportion having improved or stable qol in relevant rcts. RESULTS: We identified 906 patients with pre-ppdcesas records. Median survival was 31 weeks compared with 28-48 weeks in rcts. After accounting for deaths and cases lost to follow-up, we estimated that, at 2 months, 62% of the cohort had improved or stable well-being compared with 55%-63% who had improved or stable qol in rcts. CONCLUSIONS: The effectiveness of ppdc for nsclc in routine practice in Ontario is consistent with its efficacy in rcts, both in terms of survival and improvement in well-being.

Delivery of perioperative chemotherapy for bladder cancer in routine clinical practice.

BACKGROUND: Few articles have documented regimens and timing of perioperative chemotherapy for bladder cancer in routine practice. Here, we describe practice patterns in the general population of Ontario, Canada. METHODS: In this retrospective cohort study, treatment and physician billing records were linked to the Ontario Cancer Registry to describe use of neoadjuvant (NACT) and adjuvant (ACT) chemotherapy among all patients with muscle-invasive bladder cancer treated with cystectomy in Ontario 1994-2008. Time to initiation of ACT (TTAC) was measured from cystectomy. Multivariate Cox regression was used to identify factors associated with overall (OS) and cancer-specific survival (CSS). RESULTS: Of 2944 patients undergoing cystectomy, 4% (129/2944) and 19% (571/2944) were treated with NACT and ACT, respectively. Five-year OS was 25% [95% confidence interval (CI) 17% to 34%] for NACT, 29% (95% CI 25% to 33%) for ACT cases. Among patients with identifiable drug regimens, cisplatin was used in 82% (253/308) and carboplatin in 14% (43/308). The most common regimens were gemcitabine-cisplatin (54%, 166/308) and methotrexate, vinblastine, doxorubicin, cisplatin (MVAC) (21%, 66/308). Mean TTAC was 10 weeks; 23% of patients had TTAC >12 weeks. TTAC >12 weeks was associated with inferior OS [hazard ratio (HR) 1.28, 95% CI 1.00-1.62] and CSS (HR 1.30, 95% CI 1.00-1.69). In adjusted analyses, OS and CSS were lower among patients treated with carboplatin compared with those treated with cisplatin; OS HR 2.14 (95% CI 1.40-3.29) and CSS HR 2.06 (95% CI 1.26-3.37). CONCLUSIONS: Most patients in the general population receive cisplatin, and this may be associated with superior outcomes to carboplatin. Initiation of ACT beyond 12 weeks is associated with inferior survival. Patients should start ACT as soon as they are medically fit to do so.

First-line Palliative Chemotherapy for Colorectal Cancer: a Population-based Analysis of Delivery and Outcomes in a Single-payer Health System.

AIMS: Clinical practice guidelines recommend palliative chemotherapy for most patients with metastatic colorectal cancer. However, outcomes observed in the real world compared with patients enrolled in clinical trials have not been sufficiently described. The objective of this study was to evaluate the delivery and outcomes of first-line palliative chemotherapy administered to patients with colorectal cancer in routine clinical practice compared with clinical trials. MATERIALS AND METHODS: Using linked health administrative data, we carried out a retrospective population-level cohort study on patients diagnosed with colorectal cancer in Ontario, Canada from 2010 to 2019. Patient, disease and treatment characteristics were summarised. The primary outcome was median overall survival, stratified by treatment prescribed and age. Demographics and outcomes in this real-world population were compared with those from pivotal clinical trials. A multivariable Cox regression model reporting hazard ratios and 95% confidence intervals was used to determine factors associated with survival in patients receiving systemic treatment. RESULTS: We identified 70 987 patients with a new diagnosis of colorectal cancer, of which 4613 received first-line chemotherapy for unresectable locally advanced or metastatic disease and formed the study cohort. Fifty-eight per cent were male and the mean age was 63 years. Most had colon cancer (69%), at least one comorbidity (73%) and lived in an urban location (79%). Less than half (47%) had surgery after diagnosis. The most common regimen prescribed was folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) with bevacizumab or epidermal growth factor receptor inhibitors (EGFRi; n = 2784, 60%). Among all treated patients, the median overall survival was 17.1 months, with survival difference by regimen [median overall survival 18.3 for FOLFIRI with bevacizumab or EGFRi, 19.6 for folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX)/capecitabine, oxaliplatin (XELOX) with bevacizumab or EGFRi, 13.6 for FOLFIRI alone and 7.8 for 5-fluorouracil or capecitabine]. Patients aged >80 years were most likely to have received single-agent 5-fluorouracil or capecitabine, and had inferior overall survival compared with their younger counterparts. Compared with pivotal clinical trials, patients in the real world had inferior overall survival outcomes despite similar demographic characteristics (including age and sex). CONCLUSIONS: In this real-world population-based analysis of patients receiving first-line chemotherapy for unresectable locally advanced or metastatic colorectal cancer, survival outcomes were inferior to those reported in randomised trials despite similarities in age and sex. This information can be used when counselling patients in routine practice about expected outcomes.

Alignment of practice guidelines with targeted-therapy drug funding policies in Ontario.

BACKGROUND: We evaluated clinical practice guideline (cpg) recommendations from Cancer Care Ontario's Program in Evidence-Based Care (pebc) for molecularly targeted systemic treatments (tts) and subsequent funding decisions from the Ontario Ministry of Health and Long-Term Care. METHODS: We identified pebc cpgs on tt published before June 1, 2010, and extracted information regarding the key evidence cited in support of cpg recommendations and the effect size associated with each tt. Those variables were compared with mohltc funding decisions as of June 2011. RESULTS: From 23 guidelines related to 17 tts, we identified 43 recommendations, among which 38 (88%) endorsed tt use. Among all the recommendations, 38 (88%) were based on published key evidence, with 82% (31 of 38) being supported by meta-analyses or phase iii trials. For the 38 recommendations endorsing tts, funding was approved in 28 (74%; odds ratio related to cpg recommendation: 29.9; p = 0.003). We were unable to demonstrate that recommendations associated with statistically significant improvements in overall survival [os: 14 of 16 (88%) vs. 8 of 14 (57%); p = 0.10] or disease- (dfs) or progression-free survival [pfs: 16 of 21 (76%) vs. 3 of 5 (60%); p = 0.59] were more likely to be funded than those with no significant difference. Moreover, we did not observe significant associations between funding approvals and absolute improvements of 3 months or more in os [6 of 6 (100%) vs. 3 of 6 (50%), p = 0.18] or pfs [6 of 8 (75%) vs. 10 of 12 (83%), p = 1.00]. CONCLUSIONS: For use of tts, most recommendations in pebc cpgs are based on meta-analyses or phase iii data, and funding decisions were strongly associated with those recommendations. Our data suggest a trend toward increased rates of funding for therapies with statistically significant improvements in os.

Factors associated with referral to medical oncology and subsequent use of adjuvant chemotherapy for non-small-cell lung cancer: a population-based study.

BACKGROUND: Adjuvant chemotherapy (act) for non-small-cell lung cancer (nsclc) is associated with improved survival in the general population, but may be underutilized. We explored the factors associated with referral to medical oncology and subsequent use of act among all patients with resected nsclc in Ontario, Canada. METHODS: The Ontario Cancer Registry was used to identify all incident cases of nsclc diagnosed in Ontario during 2004-2006. We linked electronic records of treatment and of physician billing to identify surgery, act, and medical oncology consultation. A multivariate logistic regression model was used to evaluate factors associated with referral to medical oncology and subsequent use of act. RESULTS: Among 3354 cases of nsclc resected in Ontario during 2004-2006, 1830 (55%) were seen postoperatively by medical oncology, and 1032 (31%) were treated with act. Patients more than 70 years of age were less likely than younger patients to have a consultation [odds ratio (or): 0.4; p < 0.001]. A higher proportion of cases with stage ii or iii nsclc than with stage i disease were referred (ors: 2.7, 2.0 respectively; p < 0.005). We observed substantial geographic variation in the proportion of surgical cases referred (range: 32%-88%) that was not explained by differences in case mix. Among cases referred to medical oncology, older patients (age 60-69 years, or: 0.4; age 70+ years, or: 0.1; p < 0.001) with greater comorbidity (Charlson comorbidity index: 3+; or: 0.5; p < 0.05) and a longer postoperative stay (median length of stay: 7+ days; or: 0.7; p = 0.001) were less likely to receive act. Use of act was greater in patients with stage ii or iii than with stage i disease (ors: 3.0, 2.7 respectively; p < 0.001); use also varied with geographic location (range: 46%-63%). CONCLUSIONS: The initial decision to refer to medical oncology is associated with age and stage of disease, and those factors have an even greater effect on the decision to offer act. Comorbidity and postoperative length of stay were not associated with initial referral, but were associated with use of act in patients seen by medical oncology.

The current status of National Cancer Control Plans in Africa: Data from 32 countries.

BACKGROUND: Cancer incidence and mortality are rapidly rising in Africa. National Cancer Control Plans (NCCPs have contributed to a reduction in the burden of some preventable cancers, availing early diagnosis and adequate treatment modalities and palliative care, while sustaining them with sufficient monitoring systems. knowledge we undertook a cross-sectional survey across continental Africa to understand the presence of NCCPs, availability of early detection and screening policies and the status of health financing pertaining to cancer. METHODS: Through an online survey, we approached key cancer care staff in 54 countries. Questions were themed in 3 main areas - Cancer registries and national cancer control plans (NCCPs) availability in countries, Cancer screening, diagnosis and management capacity, Financing in cancer care. RESULTS: On 54 approached respondents, we received 32 responses. 88 % of responding countries have active national cancer registries, 75 % with NCCPs and 47 % with cancer screening policies and practices. Universal Health Coverage is available in 40 % of countries. CONCLUSION: Our study shows that there is a scarcity of NCCPs in Africa. Deliberate investment in cancer registry and clinical services is key to improving access to care and ultimately reduce cancer mortality in Africa.

Randomized controlled trials in the era of molecular oncology: methodology, biomarkers, and end points.

BACKGROUND: We previously reported metrics of systemic therapy randomized controlled trials (RCTs) in breast cancer, colorectal cancer (CRC), and non-small-cell lung cancer (NSCLC) published 1975-2004. To evaluate trends in the era of targeted therapies (TT), we have repeated a similar analysis of RCTs published 2005-2009. METHODS: A search for phase III RCTs of systemic agents published in five major journals 2005-2009 was carried out. Trials were classified as TT if they involved any non-hormonal targeted agent. We extracted data regarding biomarker use. Integral biomarkers were defined as tests used to determine eligibility, stratification, or allocation. Descriptive statistics were used to analyze trends over time. RESULTS: One hundred and thirty-seven eligible RCTs were evaluated. Compared with 1995-2004, the number (17-27 RCTs/year) and size (median sample size 446-722, P < 0.001) of RCTs increased. The proportion of RCTs evaluating TT increased from 4% (7/167) to 29% (40/137) (P < 0.001). There was an increase in the proportion of trials with financial support from industry [57% (95/167) to 78% (107/137), P = 0.001]. Biomarkers were included in 58% (80/137) of RCTs; integral biomarkers were included in 36% (49/137) of trials. Among the 49 RCTs using integral biomarkers, 40 (82%) used HER2 and/or ER/PR status in studies of breast cancer. CONCLUSIONS: RCTs published in 2005-2009 are larger, more likely to evaluate TT, and be supported by industry. Biomarkers may be increasingly used, but the most common use relates to traditional use of ER/PR and evolving use of HER2 in breast cancer RCTs.

Industry Funding of Oncology Randomised Controlled Trials: Implications for Design, Results and Interpretation.

AIMS: Most randomised controlled trials (RCTs) in oncology are now funded by the pharmaceutical industry. We explore the extent to which RCT design, results and interpretation differ between industry-funded and non-industry-funded RCTs. MATERIALS AND METHODS: In this cross-sectional analysis, a structured literature search was used to identify all oncology RCTs published globally during 2014-2017. Industry funding was identified based on explicit statements in the publication. Descriptive statistics were used to compare elements of trial methodology and output between industry- and non-industry-funded RCTs. RESULTS: The study sample included 694 RCTs; 71% were funded by industry. Industry-funded trials were more likely to test systemic therapy (97% versus 62%; P < 0.001), palliative-intent therapy (71% versus 41%; P < 0.001) and study breast cancer (20% versus 12%; P < 0.001). Industry-funded trials were larger (median sample size 474 versus 375; P < 0.001) and more likely to meet their primary end point (49% versus 41%; P < 0.001). Among positive trials, there were no differences in the magnitude of benefit between industry- and non-industry-funded RCTs. Trials funded by industry were published in journals that had a significantly higher median impact factor (21, interquartile range 7, 28) than non-industry-funded trials (impact factor 12, interquartile range 5, 24; P = 0.005); this persisted when adjusted for whether a trial was positive or negative. CONCLUSIONS: The vast majority of oncology RCTs are now funded by industry. Industry-funded trials are larger, more likely to be positive, predominantly test systemic therapies in the palliative setting and are published in higher impact journals than trials without industry support.