A standard therapy for locally advanced rectal cancer (LARC) includes fluoropyrimidine (FP)-based neoadjuvant chemoradiation (nCRT). Previous studies have inconsistently demonstrated that baseline neutrophil- and platelet-to-lymphocyte ratios (NLR and PLR) are predictive of response to nCRT or prognostic of outcomes in LARC. We reviewed patients with LARC undergoing nCRT followed by surgery from 2005 to 2013 across 8 Canadian cancer centres. Outcome measures of interest were pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Logistic regression and Cox proportional hazard models were used to assess for associations between baseline hematologic variables and outcomes. Of 1527 identified patients, 1237 (81%) were included in the DFS/OS analysis. Median age was 62 (range 23–88), 69% were male, and 80% had performance status (PS) 0–1. Twenty-six percent had elevated NLR (≥ 4), and 66% had elevated PLR (≥ 150). Ninety-seven percent of patients received FP-based nCRT, with 96% receiving ≥44 Gy. 81% completed neoadjuvant chemotherapy and 95% completed neoadjuvant radiotherapy, with a pCR rate of 18%. After a median follow-up time of 71 months, 8% developed local recurrence, 22% developed distant recurrence and 24% died. 5-year DFS and OS were 69% (95% CI 66–72%) and 79% (95% CI 77–82%), respectively. In multivariate analyses, elevated baseline NLR and PLR were neither prognostic for DFS and OS nor predictive of pCR. NLR and PLR were not found to be independently prognostic for DFS or OS and did not predict for pCR in patients with LARC undergoing nCRT followed by surgery.

Canada has one of the most complex and rigorous drug approval and public reimbursement processes and is, unfortunately, one of the countries with the longest delays in drug access. To assess the overall impact of systemic delays in access to cancer therapy, a targeted literature review (TLR) was performed to identify studies associated with the clinical, economic, and quality of life impacts of delayed access to oncology drugs. Using MEDLINE/PubMed databases and snowballing, four unique records met the eligibility criteria. Results revealed that clinical outcomes were the most impacted by systemic delays in access to oncology drugs (e.g., life years lost, overall survival, and progression-free survival). The four articles retrieved by the TLR specifically illustrated that a substantial number of life years could potentially be saved by increasing systemic efficiency regarding the development, approval, and reimbursement processes of new drugs for advanced malignancies. It is imperative that initiatives are put in place to improve the performance and speed of Canadian drug regulatory and health technology assessment (HTA) processes, especially for new cancer therapeutics. The proposed solutions in this paper include better coordination between HTA and Canadian payers to harmonize coverage decisions, international collaborations, information sharing, and national standards for timeliness in oncology drug access.

Cancer treatment has evolved significantly over the past decade with the emergence of a multitude of new treatments across cancer types. Alongside the pace of drug discovery, the cost of cancer drugs has also increased. In the face of this growth in development and spending, it is crucial to have an understanding of the processes and pressures new drugs navigate to get to the market in Canada. This paper is a review of the complex, multi-step regulatory and funding process undertaken by cancer drugs in Canada. It reviews the role of Health Canada, the Patented Medicine Prices Review Board, the Health Technology Assessment, the pan-Canadian Pharmaceutical Alliance, and finally, the provincial, territorial, and federal payers. Recent developments are highlighted. Strategies to minimize duplication of effort, improve timeliness, and increase efficiency are explored. The cancer drug regulatory and funding process in Canada is complex, and an understanding of the current system and ongoing evolution is essential.

Signal Transducer and Activator of Transcription-3 (STAT3) mediates cellular functions. We assessed the IHC expression of phosphorylated STAT3 (pSTAT3) in paired primary tumors and liver metastases in patients with advanced stage colorectal cancer (CRC). We included patients with tissue blocks available from both the primary CRC and a surgically resected liver metastasis. The IHC pSTAT3 expression agreement was measured using Cohen's kappa statistic. The study included 103 patients, 55% male, median age was 64. 43% tumors originated in rectum, and 63% of the primary tumors were synchronous. Expression of pSTAT3 was 76% in liver metastases and 71% in primary tumors. A difference in pSTAT3 staining between the primary tumor and liver metastases was noted in 64%. There was lost expression of pSTAT3 in the liver metastases in 28% and gained expression in 36% of cases compared to the primary. The kappa statistic comparing agreement between staining patterns of the primary tumors and liver metastases was a “less-than-chance”, at -0.02. Median survival was 4.9 years, with no difference in survival outcomes by pSTAT3 expression in the primary tumor or liver metastases. STAT3 is not a prognostic marker in the selective setting of metastatic CRC to liver, but it may remain a potential therapeutic target given most liver metastases expressed pSTAT3. Discordant pSTAT3 expression in between primary tumors and paired liver metastases suggests that use of this class of drug to treat liver predominant metastatic colorectal cancer in a biomarker-driven approach may require confirmatory liver tumor biopsy.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients’ access to best care. A modified Delphi methodology was used to identify consensus on 30 questions involving five themes: accountability, disparities, endpoints, timeliness, and cost-effectiveness. It was agreed that greater transparency is required across regulatory and HTA processes. Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding. Canadian health care providers request improvements in timely access to life-saving therapeutics in line with other comparator countries. Clinicians expect urgent improvements in Canadian health systems to give our patients their best chance of survival.

Background: Canada has a publicly funded healthcare system with a complex drug funding process. After Health Canada approval to market a drug, the pan-Canadian Oncology Drug Review (pCODR) (now renamed the CADTH reimbursement review) makes a non-binding funding recommendation to the Canadian provinces (except Quebec), which each then decide whether the drug will be publicly funded. We identified the determinants of funding in this process. Methods: We analyzed drugs for advanced lung (n = 15), breast (n = 8), colorectal (CRC) (n = 7), melanoma (n = 10), and neuroendocrine (NET) (n = 3) cancers undergoing the funding decision process from 2011 to 2019. Determinants of funding assessed in the model included list price, cancer type, drug class, and pCODR recommendation. The primary outcome was the correlation between list price and time to funding (TTF: Health Canada approval to first provincial funding). Secondary outcomes included an exploratory analysis of predictors of drug funding. Results: We analyzed 43 drugs: targeted agents 72%, immunotherapy 20%, chemotherapy 7%. A total of 72% were funded in at least one province. Median TTF was 379 days (IQR 203–601). Median list price (28-day course) was CAD 8213 (IQR CAD 5391–9445). Higher list price was not correlated with TTF (correlation coefficient −0.20, p = 0.28). There was no association between list price and pCODR recommendation or the decision to fund in at least one province. A positive pCODR recommendation correlated with the provinces’ funding decisions (p < 0.001), where 89% of drugs with a positive recommendation were funded and 100% of drugs with a negative recommendation were not funded. Tumor type was predictive of TTF (p < 0.001): CRC drugs were the slowest at a median of 2541 days (IQR 702–4379), and NETs were the quickest at a median of 0 days (IQR 0–502). Cancer type predicted decision to fund in at least one province (p = 0.005), with funding for 100% of NET drugs at the high end and 29% of CRC drugs at the low end. Drug class was predictive of TTF (p = 0.01): 465 days (IQR 245–702) for targeted agents, 443 days (IQR 298–587) for chemotherapy, and 339 days (IQR 164–446) for immunotherapy. Conclusions: Determinants of drug funding included cancer type, drug class, and pCODR recommendation but not list price. Factors other than cost were more heavily weighted in the funding decisions of cancer drugs in Canadian provinces.