The following colorectal cancer research updates extend from November 20th, 2019 to February 16th, 2020 inclusive and are intended for informational purposes only.
DRUGS / SYSTEMIC THERAPIES
- Low-Dose Aspirin Might Cut Cancer Risk, Especially for Overweight People
- Phase II LEAP Clinical Trial to Treat mCRC
- BEACON Results Light Way for Chemo-Free Therapy in Colorectal Cancer
- Health Canada approves VITRAKVI (Larotrectinib), first tumour agnostic cancer treatment for advanced solid tumours harbouring an NTRK gene fusion
- Larotrectinib Efficacy Confirmed in TRK+ GI Cancer
- Encorafenib (Braftovi) Plus Cetuximab (Erbitux) Moves Forward For Review By FDA For Metastatic BRAF-Mutant Colorectal Cancer Without Binimetinib
- Study Finds Older Adults Less Likely to Receive Second-Line Therapy for Metastatic Colorectal Cancer
- A Phase II, Open-Label, Multicentre, Study of an Immunotherapeutic Treatment for the MSI High Colorectal Cancer Metastatic Population
- Taiho Oncology Presents Data on LONSURF® (trifluridine and tipiracil) and Futibatinib (TAS-120) at ASCO 2020 Gastrointestinal Cancers Symposium (ASCO GI)
- Phase III Study at the Odette Cancer Centre Comparing Arfolitixorin vs Leucovorin: Both in Combination with 5FU, Oxaliplatin and Bevacizumab in Patients with Advanced Colorectal Cancer
- Bevacizumab (Avastin) In Combination With Trifluridine/Tipiracil (FTD/TPC, Lonsurf), Improves Survival in Refractory Colorectal Cancer
- Hepatic Artery Infusion Pump (HAIP) Chemotherapy Program – Sunnybrook Hospital
- Living Donor Liver Transplantation for Unresectable Colorectal Cancer Liver Metastases
RADIATION THERAPIES/INTERVENTIONAL RADIOLOGY
- Study Offered at the Odette Cancer Centre to Treat Recurrent Rectal Cancer
- Kaiser Permanente Research Suggests Clinicians Should Ask About Cancer Patients’ Support Systems
- Young Adult Colorectal Cancer Clinic Available at Sunnybrook Hospital
- Exercise For adults Diagnosed With Rectal Cancer: A Feasibility Study
- High dose vitamin D supplementation in Stage 4 colorectal cancer patients
- SUNSHINE trial: high-dose vitamin D may benefit patients with metastatic colorectal cancer
- Study Looking for Female Survivors to participate in an Exercise Program
- Low-Dose Fish Oil No Help in Cutting Adenoma Risk, But African Americans And Those With Low Plasma Omega-3 Levels Might Benefit
DRUGS / SYSTEMIC THERAPIES
- Low-Dose Aspirin Might Cut Cancer Risk, Especially for Overweight People (Dec. 2018)
According to researchers in a new study, taking Aspirin three or more times a week is associated with not only lower risk of cancer death, but death for any reason. The recent study was conducted at the National Cancer Institute (NCI) by Dr. Holli Loomans-Kroop. The study data, repurposed from a 1993-2008 Prostate, Lung, Colorectal, and Ovarian Cancer screening trial with well over 146,000 participants, was re-analyzed by Loomans-Kroop towards brand new findings. “Our primary focus was really on colorectal cancer deaths since there is much evidence to suggest that Aspirin use may lower the risk of gastrointestinal deaths,” said Loomans-Kropp. The results show that Aspirin is most notably protective in the overweight — specifically those with a body mass index of 25 to 29.9. All causes of death were reduced by 19%, and overall cancer-related deaths were reduced by 15%. Within the overweight participants involved in the study, the risk of gastrointestinal cancer reduced by (28%) and colon cancer (34%). The study results support the standing recommendation of the U.S. Preventive Services Task Force (USPSTF), which says people 50 to 59 (if not at risk for bleeding) should take low-dose Aspirin to prevent colon cancer.
No one knows why Aspirin might have this protective effect, but Loomans-Kropp stated that evidence does point to Aspirin’s anti-inflammatory action. She adds, “Gastrointestinal cancers are highly inflammation-associated cancers, and where the strongest effect has been with the gastrointestinal cancers.”
Some points to consider from the American Cancer Society:
- Aspirin may help prevent cancer in much the same way it prevents heart attacks (by blocking the activation of blood platelet cells)
- Activated platelets release factors that help tumors to grow, so they may also help cancers spread
- Those concerned about colon cancer should talk to their doctor about screening so that polyps if found, can be removed before they have a chance to develop into cancer
- a healthy weight, being physically active, quitting smoking, and eating less red meat also can help reduce risk
Please note: Anyone thinking about taking daily Aspirin should discuss it with their doctor before do so. and please discuss the benefits versus harm with your physician when considering individual health issues and bleeding risks.
- Phase II LEAP Clinical Trial For mCRC (Sept. 20/19)
The purpose of this study is to determine the safety and efficacy of combination therapy with pembrolizumab (MK-3475) and Levantine (E7080/MK-7902) in patients with triple negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma (GBM), or biliary tract cancers (BTC). Participants will be enrolled into initial tumor-specific cohorts which will be expanded if adequate efficacy is determined. The trial is available at the Odette Cancer Centre and at the Princess Margaret Cancer Centre in Toronto as well as the following Centres throughout Canada: Abbotsford, BC; Winnipeg, MB; CHU de Quebec. For information, visit the link below.
- BEACON Results Light Way for Chemo-Free Therapy in Colorectal Cancer (Aug. 1/19)
New results from the BEACON clinical trial offer hope for a chemotherapy-free treatment option for certain patients with colorectal cancer (CRC). Combinations of targeted therapies yielded significantly improved response rates and overall survival rates compared with traditional chemotherapy regimens among patients with previously treated BRAF V600E–mutated metastatic CRC. This BRAF V600E mutation is found in 10% to 15% of metastatic CRC patients and is usually associated with a poor prognosis. The BEACON trial had three treatment arms.
One group (Group I) of patients received triplet therapy with three targeted agents —
- the BRAF inhibitor encaenia (Braftovi, Array BioPharma),
- the MEK inhibitor binimetinib (Mektovi, Array BioPharma), and
- the EGFR inhibitor monoclonal antibody cetuximab (Erbitux, Eli Lilly).
Another group (Group II) received doublet targeted therapy with encorafenib and cetuximab.
A third (control) group received standard chemotherapy (FOLFIRI).
The new results, presented at the World Conference on Gastrointestinal Cancer (WCGC) 2019, were from an initially unplanned interim analysis. Presenter Scott Kopetz, MD, PhD, from the University of Texas MD Anderson Cancer Center, Houston, showed that the triplet therapy was associated with a remarkable 48% improvement in overall survival vs standard chemotherapy. Furthermore, progression-free survival (PFS) was improved by 62%, at 4.3 months with the triplet regimen vs 1.5 months with standard therapy. This improvement was reflected in a highly significant increase in the objective response rate (ORR) with triplet therapy, at 26%. ORR increased to 34% among patients who had previously received just one therapy. It was only 2% with chemotherapy. Importantly, these improvements were achieved without increasing toxicity, Kopetz added.
The triplet therapy has already been added to the National Comprehensive Cancer Network (NCCN) guidelines for the treatment of metastatic CRC. Hence, this is now available to U.S.-based patients for treatment of this difficult disease. The BEACON trial is active in Canada but is no longer recruiting. Please see the following link: https://clinicaltrials.gov/ct2/show/study/NCT02928224?show_locs=Y#locn
- Health Canada Approves VITRAKVI (Larotrectinib), First Tumour Agnostic Cancer Treatment For Advanced Solid Tumours Harbouring an NTRK Gene Fusion (Sept. 19/19)
Bayer announced that there is now a treatment in Canada for tyrosine receptor kinase fusion protein-driven childhood and adult cancers. Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusions can result in the production of TRK fusion proteins that can lead to uncontrolled cell growth and cancer. Health Canada issued a Notice of Compliance with Conditions (NOC/c) for VITRAKVI® (Larotrectinib). VITRAKVI® is approved for the treatment of adult and pediatric patients with solid tumours that have an NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory treatment options. Treatment with VITRAKVI® should be initiated following confirmation of an NTRK gene fusion in a tumour specimen using a validated test.
This is the first time Health Canada has approved a tumour agnostic treatment, such that patients with advanced solid tumours harbouring an NTRK gene fusion may be eligible for treatment with VITRAKVI®, across multiple tumour types and ages. VITRAKVI® is a first-in class oral and highly selective TRK inhibitor that may shrink the tumour or may slow or stop it from growing. In the clinical trials that were the basis for this approval, TRK fusion cancer patients treated with Larotrectinib experienced clinical benefit across numerous tumour types, including lung, thyroid, melanoma, GIST (gastrointestinal stromal tumour), colon, soft tissue sarcoma, salivary gland, and infantile fibrosarcoma. The overall response rate (ORR) was 75% (95% CI, 64%, 85%) with 22% of patients experiencing a complete response (CR) to treatment. The ORR observed was 90% in pediatrics and 69% in adults, and responses were rapid and durable.
What is TRK Fusion Cancer?
TRK fusion cancer is rare and occurs when an NTRK gene fuses with another unrelated gene, producing a TRK fusion protein that becomes constitutively active or overexpressed, triggering a signaling cascade. These TRK fusion proteins act as oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer, regardless where it originates in the body. TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body. TRK fusion cancer occurs in various adult and pediatric solid tumours with varying frequency, including lung, thyroid, gastrointestinal cancers (colon, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (mammary analogue secretory carcinoma) and pediatric cancers (infantile fibrosarcoma and soft tissue sarcoma). TRK fusion proteins are rare in common cancers (such as colorectal cancer) and common in rare cancers.
NB: The pan Canadian Oncology Drug Review Expert Committee (pERC) has recently issued a funding recommendation in respect of Larotrectinib. It conditionally recommends the reimbursement of Larotrectinib (Vitrakvi) for the treatment of adult and pediatric patients with locally advanced solid tumors that have an NTRK gene fusion This recommendation pertains only to adult and pediatric patients with salivary gland tumours, adult or pediatric patients with soft tissue sarcoma (STS) and pediatric patients with cellular congenital mesoblastic nephroma or infantile fibrosarcoma, without a known acquired resistance mutation, that are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory treatment options, only if the following conditions are met:
- Cost-effectiveness being improved to an acceptable level
- Feasibility of adoption (budget impact and access to testing) is addressed
Stay tuned as the expert committee is currently reviewing feedback submissions from various stakeholders.
Please note: the expert review committee has as of October 31st, 2019 issued a final negative funding recommendation in respect of Larotrectinib. Efforts are currently underway to assemble a massive campaign to address this final recommendation by working to secure a sustainable, long-term funding solution for TRK fusion cancer patients.
- Bayer has launched a testing program called FastTRK. As per an information sheet that may be obtained from CCRAN, FastTRK is a clinical testing program for the diagnosis of NTRK gene fusions. Sponsored by Bayer, this is a complimentary service for clinicians to determine whether their patients’ cancer has an NTRK gene fusion. Solid tumour samples from eligible patients (in the form of a solid tumour block or prepared slides) will be tested by immunohistochemistry (IHC) and/or next generation sequencing (NGS). Currently, Bayer has partnered with LifeLabs and the Kingston Health Sciences Centre (KHSC) to provide NTRK gene fusion testing services for Canadians. The FastTRK program will be supported at least until the end of 2021.
- Bayer will continue to offer the therapy to patients who are identified to have TRK fusion cancers and who are responding to the therapy.
- Bayer will provide a TRAKTION Patient Support Program to assist patients while on the therapy.
5. Larotrectinib Efficacy Confirmed in TRK+ GI Cancer (Jan. 24/20)
The efficacy of larotrectinib (Vitrakvi) has been confirmed in patients with heavily pretreated TRK fusion-positive gastrointestinal (GI) cancers. At the 2020 Gastrointestinal Cancers Symposium, researchers provided a report about a subset of patients with GI cancer. Patients participated in 1 of 3 clinical trials using the selective TRK inhibitor (where the patient had been pretreated for locally, advanced or metastatic solid tumors). Their overall response rate (ORR) was: 50% in patients with colon cancer.
Among responders, the median time to response was 1.8 months (range, 1.7-2.1). The duration of response ranged from 3.5 to more than 14.7 months, and the time of treatment ranged from 0.9 to more than 19.0 months. At a median follow-up of 19.0 months, the median overall survival was 33.4 months in this subset of patients with TRK fusion-positive GI cancers. Researchers stated that this trial proved that GI cancer patients are no different than other cancer patients with TRK fusion cancers — and that larotrectinib provides evidence of durable response. Though TRK fusions are very rare and occur in <1% of all solid tumors, this finding is useful in these circumstances. Fourteen patients with TRK fusion-positive GI cancers from a total of 159 enrolled patients treated on either the NCT02122913, SCOUT (NCT02637687), or NAVIGATE (NCT02576431) trials formed the population for this analysis. All were administered with oral larotrectinib at 100 mg twice daily, until disease progression, withdrawal, or unacceptable toxicity. “Across cancers, I believe that if patients have good performance status and have the potential to be treated, it’s worthwhile to do next-generation sequencing [NGS]. I think TRK fusions are among the things you should be testing for,” Berlin said. “It’s a rare cohort, but because the drug can work, it’s hard to say that you should miss that.” Seven of the eight patients with colon cancer were microsatellite instability (MSI)-high, which is consistent with the literature showing that “patients with TRK fusion cancer are predominantly identified in the MSI-high subset of patients with colorectal cancer,” said Berlin.
What is larotractenib (Vitrakvi)?
Larotrectinib is a first-in-class, selective inhibitor of TRK for the treatment of adult and pediatric patients with TRK fusion-positive cancers. 2 TRK fusions are oncogenic (tumor-causing) drivers of various adult and pediatric tumors. They arise from rearrangements between neurotrophic tyrosine receptor kinase (NTRK) 1, 2, or 3 genes and an unrelated gene. In a primary analysis of 55 patients with tumors harboring TRK fusions, larotrectinib exhibited tumor agnostic activity in 17 distinct tumor types with an investigator-assessed ORR of 80%.3 That rate was confirmed in the expanded dataset, said Berlin.
What is Tumor Agnostic Therapy?
A type of therapy that uses drugs or other substances to treat cancer based on cancer’s genetic and molecular features without regard to the cancer type or where the disease started in the body.
In TRK fusion cancer, the NTRK gene fuses with an unrelated gene, causing overexpression of the oncogenic TRK fusion protein. https://blog.seracare.com/ngs/presenting-ntrk-reference-materials-for-global-assay-standardization-at-aacr-2019
Image Source: https://pharma.bayer.com/trk-fusion-cancer
- Encorafenib (Braftovi) Plus Cetuximab (Erbitux) Moves Forward For Review By FDA For Metastatic BRAF-Mutant Colorectal Cancer Without Binimetinib (Jan. 25/20)
Only the two-drug combination (doublet) of encorafenib (Braftovi) plus cetuximab (Erbitux) will undergo regulatory review by the FDA for metastatic BRAF-mutant colorectal cancer at this time. Adding binimetinib (as a triplet) had little effect on patient survival. (Please refer to Update 3 for the original full description of the study). According to Scott Kopetz, MD, Ph.D., of MD Anderson Cancer Center in Houston, the decision follows updated results. These findings are based on the three-arm BEACON CRC trial, a phase III study, and show that the BRAF/EGFR-inhibiting doublet reached a median overall survival (OS) of 9.3 months. BEACON CRC was a global, open-label study (May 2015 to January 2019) involving randomized 665 patients with BRAF V600E-positive metastatic colorectal cancer. (see study details below). At the Gastrointestinal Cancers Symposium (GICS), Kopetz indicated the importance of sharing this information with the community. It was based on these results that binimetinib [triplet] will not be sent for review to the FDA. The use of encorafenib in conjunction with cetuximab, however, is indeed under review with the FDA. In summary, there were no discernible survival curves, and Kopetz has assumed the use of encorafenib (Braftovi) plus cetuximab (Erbitux) without binimetinib in the patient cases that meet these criteria. At a median follow-up of 12.8 months, both the chemotherapy-free doublet and triplet showed a significant improvement in median OS compared with the study’s control arm (5.9 months), an investigator’s choice of cetuximab plus either irinotecan or FOLFIRI (folinic acid, fluorouracil, and irinotecan).
GICS discussant Christopher Booth, MD, of Queen’s University in Kingston, Canada, questioned the cost-effectiveness of either treatment regimen. He argues that BRAF-mutant disease effects few colorectal cancer patients to begin with (around 400 in the U.S. each year), would likely be unaffordable to most, and would only benefit a small subgroup within this rare subset. Booth calculated the “financial toxicity” based on Red Book costs, estimating that a 28-day supply would reach $23,000 for the doublet and $32,000 for the triplet, an average treatment course would cost $109,000 and $168,000, respectively, and annual costs would balloon to $280,000 and $305,000. Kopetz’ presentation was primarily devoted to quality of life (QOL), and patient-reported outcomes data from BEACON CRC.
About BEACON CRC
BEACON CRC was a global, open-label study that from May 2015 to January 2019 that randomized 665 patients with BRAF V600E-positive metastatic colorectal cancer to one of thee arms in the second-line setting: encorafenib (300 mg daily) plus cetuximab (400 mg/m2 as an initial dose, then 250 mg/m2) and binimetinib (45 mg twice daily) in the triplet arm, encorafenib plus cetuximab in the doublet arm (same doses), or investigator’s choice of cetuximab plus either irinotecan or FOLFIRI in the control arm.
7. Older Adults Are Less Likely to Receive Second-Line Therapy for Metastatic Colorectal Cancer, Study Reports (Jan. 24/20)
Older adults and patients with an Eastern Cooperative Oncology Group (ECOG) performance status higher than 1 were less likely than their younger peers to receive second-line therapy for metastatic colorectal cancer (mCRC). This finding has been derived from the analysis of 10 first-line trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) Clinical Trials Program. Over 5200 patients from advanced colorectal cancer trials were examined to see if there were differences in older adults (about 16.4 percent of all study patients) versus younger adults receiving second-line therapies following disease progression. The investigators also compared time to initial progression (TTiP), time to progression, and overall survival across groups, adjusting for age, sex, ECOG performance status, the number of metastatic sites present, as well as for the evidence of metastatic lesions in the lungs, liver, or peritoneum. In short, they found younger adults were more likely than their older peers to receive subsequent therapy after disease progression following frontline therapy. Results of a multivariate analysis revealed that the “odds of receiving second-line therapy decreased by 11% for each additional decade of life”. However, though the odds of receiving a second treatment were higher for younger patients compared with older patients, it did not appear to meaningfully influence TTP (5.2 months vs. 5.1 months, respectively) nor mean overall survival (12.4 months vs. 11.6 months, respectively) between patients subsets.
Future research should examine the influence of factors such as:
- patient comorbidity
- functional status on survival outcomes
- incorporating a geriatric assessment tool to guide the selection of older adults who would be most likely to benefit from second-line therapy in mcrc.
- A Phase 2, Open-label, Multicenter, Study of an Immunotherapeutic Treatment for the MSI High Colorectal Cancer Metastatic Population (Nov. 16/19)
The purpose of this study is to look at the effectiveness of the vaccine DPX-Survivac in combination with the drugs cyclophosphamide and the immunotherapy Pembrolizumab in patients with solid cancers who are identified to be MSI-High. All patients will receive combination therapy of DPX-Survivac, cyclophosphamide, and pembrolizumab. Patients participating will know which treatment they are receiving. The trial is currently hosted at the Odette Cancer Centre and a new site is opening at Mt. Sinai Hospital.
- Taiho Oncology Presents Data on LONSURF® (trifluridine and tipiracil) and Futibatinib (TAS-120) at ASCO 2020 Gastrointestinal Cancers Symposium (ASCO GI) (Jan. 25/20)
On Jan. 25, 2020 Taiho Oncology announced the global Phase III TAGS and RECOURSE trials evaluating LONSURF® (trifluridine and tipiracil) in patients with metastatic colorectal cancer (mCRC), as well as metastatic gastric or gastroesophageal junction cancer (mGC/GEJC). Updates were also presented on two (2) trials in progress with futibatinib:
1) Phase III FOENIX-CCA3 study of futibatinib as first-line treatment for patients with advanced cholangiocarcinoma (CCA) harboring FGFR 2 gene rearrangements
2) and a Phase II basket study of futibatinib in patients with advanced solid tumors harboring FGFR genomic aberrations.
Findings were highlighted at the ASCO 2020 Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco on January 23-25, 2020.
LONSURF Pooled Safety Analysis
The pooled safety analysis of the TAGS and RECOURSE trials determined that hematologic adverse events with LONSURF in subgroups of patients with mild to moderate renal impairment and mild hepatic impairment were manageable and similar to those in the overall patient population. Karin Blakolmer, MD, MBA, Senior Vice President and Head of Medical Affairs, Taiho Oncology, Inc. reiterated the importance of safety, and how any hematologic side effects of these trials were in line with the overall patient population and manageable in the same way. Blakomer further stated that this was positive news for people living with metastatic colorectal cancer and metastatic gastric cancer who are receiving treatment with LONSURF
- Phase III Study at the Odette Cancer Centre Comparing Arfolitixorin vs Leucovorin in Combination with 5FU, Oxaliplatin and Bevacizumab in Patients with Advanced Colorectal Cancer (Nov. 12/10)
The purpose of this study is to look at the effectiveness of the drug Arfolitixorin in combination with 5-fluorouracil (5FU), oxaliplatin, and bevacizumab in patients with colorectal cancer. Patients with advanced/metastatic colorectal cancer who meet certain criteria may be able to participate. There will be two groups of patients participating in this study;
- one group will receive Arfolitixorin in combination with 5FU), oxaliplatin, and bevacizumab,
- while the other group will receive the drug Leucovorin in combination with 5FU, oxaliplatin, and bevacizumab (standard of care).
The doctor and study staff will not know which group a patient is in. Patients will be randomized to receive one treatment or the other.
Arfolitixorin is Isofol’s proprietary drug candidate being developed to increase the efficacy of standard of care chemotherapy for advanced colorectal cancer. The drug candidate is currently being studied in a global Phase 3 clinical trial. As the key active metabolite of the widely used folate-based drugs, arfolitixorin can potentially benefit all patients with advanced colorectal cancer, as it does not require complicated metabolic activation to become effective.
Treating cancer patients with arfolitixorin – The goals:
- When treating colorectal cancer, for example, arfolitixorin is administered in combination with 5-FU to increase cell mortality in circulating cancer cells and in cancerous tumours.
• Arfolitixorin is administered in conjunction with rescue therapy after high-dose treatment with the cytotoxic agent, methotrexate, in order to suppress the cytotoxic effect in surrounding healthy tissue. The treatment is used for certain types of cancer, such as osteosarcoma, a type of bone cancer. This involves administering arfolitixorin separately, 24 hours after the chemotherapy.
- Bevacizumab (Avastin) In Combination With Trifluridine/Tipiracil (FTD/TPC, Lonsurf), Improves Survival in Refractory Colorectal Cancer (Jan. 28/20)
Investigators are suggesting FTD/TPC-bevacizumab (Avastin) as a new standard of care. In a randomized trial of patients with chemorefractory metastatic colorectal cancer (mCRC), Avastin was added to trifluridine/tipiracil (FTD/TPC, Lonsurf). As a result, a significant improvement in progression-free survival (PFS) has been observed. The goal of therapy for chemorefractory metastatic CRC is to prevent tumor progression and prolong survival without compromising the quality of life. Both FTD/TPC and regorafenib (Stivarga) have been shown to prolong PFS and OS versus best supportive care for patients who received all available standard therapies. In this particular study, very similar serious adverse events (SAEs) occurred as in patients treated with monotherapy (one drug) or the combination of the two drugs without Avastin. Median PFS increased from 2.6 months with FTD/TPC monotherapy to 4.6 months with FTD/TPC plus bevacizumab. Median overall survival (OS, a secondary endpoint) also improved with the addition of bevacizumab (9.4 vs. 6.7 months), reported Per Pfeiffer, Ph.D., of the University of Southern Denmark in Odense, and colleagues. The fact that the trial is a small phase II study of fewer than 100 patients from four centers in Denmark should be noted as a limitation.
Additionally, hospitalization was required in a larger number of participants (~40% in both groups), according to Cathy Eng, MD, of Vanderbilt-Ingram Cancer Center in Nashville. Though the cause of hospitalization was not fully attributed, neutropenia is suspect. Despite the promising results of the study, more data is required before considering a change in current treatment guidelines for metastatic CRC, she concluded.
What is chemorefractory mCRC?
Chemorefractory mcrc is defined as the clinical setting in which patients with advanced disease have either progressed on or demonstrated intolerance to fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and if wild-type for KRAS, an anti–epidermal growth factor receptor therapy such as panitumumab or cetuximab.
What is Neutropenia?
An unusually low concentration of neutrophils (a type of white blood cell) in the blood. The majority of circulating white blood cells are neutrophils. They act as the primary defense against infections by destroying any bacteria, bacterial fragments, and/or immunoglobulin-bound viruses in the blood. The authors of the study feel the results are encouraging and potentially represent a novel treatment option for patients with refractory metastatic colorectal cancer. This combination is also being studied in earlier treatment lines for patients with metastatic colorectal cancer.
- Hepatic Artery Infusion Pump (HAIP) Chemotherapy Program — Sunnybrook Odette Cancer Centre (Oct. 15/19)
The HAIP program is a first-in-Canada for individuals where colon or rectal cancer (colorectal cancer) has spread to the liver and cannot be removed with surgery. The program involves a coordinated, multidisciplinary team approach to care, with close collaboration across surgical oncology, medical oncology (chemotherapy), interventional radiology, nuclear medicine, and oncology nursing. The Hepatic Artery Infusion Pump (HAIP) is a small, disc-shaped device that is surgically implanted just below the skin of the patient and is connected via a catheter to the hepatic (main) artery of the liver. About 95 percent of the chemotherapy that is directed through this pump stays in the liver, sparing the rest of the body from side effects. Patients receive HAIP-directed chemotherapy in addition to regular intravenous (IV) chemotherapy (systemic chemotherapy), to reduce the number and size of tumours. Drs. Paul Karanicolas and Yooj Ko are the program leads and happy to see patients eligible for the therapy.
Presently at Sunnybrook Odette Cancer Centre, HAIP is being used in patients with colorectal cancer that has spread to the liver that cannot be removed surgically and has not spread to anywhere else in the body. Patients who have few (1-5) and very small tumors in the lungs may be considered if the lung disease is deemed treatable prior to HAIP. If you believe you may benefit from this therapy and/or would like to learn more about the clinical trial, your medical oncologist or surgeon may fax a referral to 416-480-6179. For more information on the HAIP clinical trial, please click on the link provided below.
- Living donor liver transplantation for unresectable colorectal cancer liver metastases (Oct. 16/19)
Approximately half of all colorectal cancer (CRC) patients develop metastases, commonly to the liver and lung. Surgical removal of liver metastases (LM) is the only treatment option, though only 20-40% of patients are candidates for surgical therapy. Surgical therapy adds a significant survival benefit, with a 5-year survival after liver resection for LM of 40-50%, compared to 10-20% 5-year survival for chemotherapy alone. Liver transplantation (LT) would remove all evident disease in cases where the colorectal metastases are isolated to the liver but considered unresectable.
Image Source: https://www.slideshare.net/AhmedAdel65/preoperative
While CRC LM are considered a contraindication for LT at most cancer centers, a single center in Oslo, Norway demonstrated a 5-year survival of 56%. A clinical trial sponsored by the University Health network in Toronto will offer live donor liver transplantation (LDLT) to select patients with unresectable metastases limited to the liver and are non-progressing on standard chemotherapy. Patients will be screened for liver transplant suitability and must also have a healthy living donor come forward for evaluation. Patients who undergo LDLT will be followed for survival, disease-free survival and quality of life for 5 years and compared to a control group who discontinue the study before transplantation due to reasons other than cancer progression. Despite the trial’s negative outcome, investigation of HIPEC, and other strategies to prevent peritoneal metastasis, should continue, they concluded in Lancet Gastroenterology & Hepatology. “The 21% peritoneal recurrence noted in the overall study population indicates the magnitude of the clinical problem in locally advanced colon cancer, and therapeutic strategies have to be further explored,” they said. “Outcomes of other trials investigating adjuvant HIPEC are eagerly awaited.”
RADIATION THERAPIES/INTERVENTIONAL RADIOLOGY
- Study Offered at the Odette Cancer Centre to Treat Recurrent Rectal Cancer (Oct. 14/19)
Magnetic resonance-guided focused ultrasound (MRg-FU) is a noninvasive, outpatient modality being investigated for the thermal treatment of cancer. In MRg-FU, a specially designed transducer is used to focus a beam of low intensity ultrasound energy into a small volume at a specific target site in the body. MR is used to identify and delineate the tumour, focus the ultrasound beam on the target and provide real-time thermal mapping to ensure accurate heating of the designated target with minimal effect to the adjacent healthy tissue. The focused ultrasound beam produces therapeutic hyperthermia (40-42°C) in the target field causing protein denaturation and cell damage. Currently, there is no prospective clinical data reported on the use of MRg-FU in the setting of recurrent rectal cancer. Recurrent rectal cancer is a vexing clinical problem. Current retreatment protocols have limited efficacy. The addition of hyperthermia
to radiation and chemotherapy may enhance the therapeutic response. With recent advances in technology, the investigators hypothesize that MRg-FU is technically feasible and can be safely used in combination with concurrent reirradiation and chemotherapy for the treatment of recurrent rectal cancer without increased side-effects. The study is being offered at the Odette Cancer Centre. Here is the link to the study protocol:
15. Kaiser Permanente Research Suggests Clinicians Should Ask About Cancer Patients’ Support Systems (Jan. 23/20)
Low social support is linked to higher mortality in post-menopausal women with colorectal cancer. Furthermore, it was determined that the women in the study were more likely to die from their disease or any cause if they had low social support before diagnosis. Over 1,400 women participated in the national long-term health study, The Women’s Health Initiative. Female patients from Kaiser Permanente and other health systems participated in the study, which was published in the journal Cancer on January 23, 2020.
Findings revealed that women who reported low social support had a 52% higher overall mortality than those who reported high levels of support, and 42% higher mortality from colorectal cancer specifically.
The results confirm previous research suggesting a role for social support for patients with serious illness, said lead author Candyce Kroenke, MPH, ScD, a research scientist with the Kaiser Permanente Division of Research. Candyce Kroenke, MPH, ScD, research scientist with the Division of Research, states, “These findings support the idea that women who have supportive friends and family around them when they are diagnosed do better”.
To gain a better understanding, the researchers set out to examine specifics of the women’s connections, their links with the community, and their living status.
Higher mortality rates were found where women lacked:
- Emotional support: caring and concern
- Informational support: help provided through information
- Tangible support: help with tasks, chores, or physical needs
- Positive interaction: someone for the patient to have fun with and take their mind off their illness
In looking at social integration, researchers found that having a partner or engaging with their community or in a religious organization was associated with a lower risk of death from rectal cancer but not colon cancer.
Similarly, the analysis found that living alone was associated with higher mortality in patients with rectal cancer. Kroenke said these different findings for rectal and colon cancer need to be replicated.
For patients, the study’s message is to lean on others when dealing with a serious diagnosis. “You can and should ask for support instead of going it alone,” Kroenke said.
For medical practitioners, the findings are a reminder that social support is an essential determinant of outcomes, Kroenke said. “Clinicians can identify patients who are at risk of low social support and provide them with additional resources,” she said. Resources might include a therapist to help with the emotional burden of cancer treatment or social services to provide logistical help, such as rides to the doctor.
Kaiser Permanente patients in Northern California diagnosed with cancer undergo a 22-point evaluation of their practical, family, emotional, and spiritual support. After treatment, cancer patients receive personalized survivorship care, including social and emotional support.
- Young Adult Colorectal Cancer Clinic Available at Sunnybrook (Nov. 14/19)
A recent study led by University of Toronto doctors has observed a rise in colorectal cancer rates in patients under the age of 50. The study mirrors findings from the U.S., Australia and Europe. The growing colorectal cancer rates in young people come after decades of declining rates in people over 50, which have occurred most likely due to increased use of colorectal cancer screening (through population-based screening programs) which can identify and remove precancerous polyps. Patients diagnosed under the age of 50 have a unique set of needs, challenges and worries. They are unlike those diagnosed over the age of 50. Dr. Shady Ashamalla (colorectal cancer surgical oncologist), and his team at the Sunnybrook Health Sciences Centre understand the needs of this patient population.
Dr. Ashamalla belongs to a multidisciplinary team of experts in the Young Adult Colorectal Cancer Clinic who will work with young colorectal cancer patients, regardless of disease stage, to create an individualized treatment plan to support each patient through their cancer journey. Their needs and concerns will be addressed as they relate to:
- Fertility concerns and issues
- Young children at home
- Dating/intimacy issues
- Challenges at work
- Concerns about hereditary cancer
- Relationships with family and friends
- Psychological stress due to any or all of the above
The team of experts consists of:
- Oncologists (medical, surgical, radiation)
- Social workers
- Nurse navigator
Should a patient wish to be referred to Sunnybrook, they may have their primary care physician, or their specialist refer them to Sunnybrook via the e-referral form which can be accessed through the link appearing below. Once the referral is received, the Young Adult Colorectal Cancer Clinic will be notified if the patient is under the age of 50. An appointment will then be issued wherein the patient will meet with various members of the team to address their specific set of concerns.
- Exercise For Adults Diagnosed With Rectal Cancer: A Feasibility Study (Oct. 30/19)
The purpose of the study is to examine the safety and feasibility of a supervised 12-week exercise intervention for adults diagnosed with rectal cancer. The exercise program will take place at the Behavioural and Metabolic Laboratory (200 Lees Ave., Ottawa) 3x a week and will be tailored to each individual.
Below are the inclusion criteria for the study:
- Men and women 18 to 85 years of age;
- Diagnosed with stage I-III rectal cancer and currently undergoing treatment or have completed treatments with the last 5 years;
- Able to read/understand English or French;
- Live <50km of the University of Ottawa;
- Approval of healthcare provider to participate in the intervention.
Individuals will be asked to complete a brief questionnaire and physical assessments (e.g., resting blood pressure) before and after the 12-week intervention.
- High dose Vitamin D supplementation in Stage 4 Colorectal Cancer Patients (Nov. 15/19)
A large body of evidence suggests that high blood levels of Vitamin D decreases the risk of developing cancer, especially colorectal cancer. Very little is known about what role optimum blood levels of Vitamin D can play in the treatment of cancer. The purpose of this clinical trial is to study the therapeutic effect and the safety of high-dose vitamin D supplementation in stage 4 (metastatic) colorectal cancer patients. Who is eligible to participate? Anyone who has a stage four colorectal cancer diagnosis, living in Ontario or British Columbia, may be eligible to participate. All participants need to have access to a Lifelabs facility for blood and urine collections. What is involved? This 40-month study involves regular lab tests and follow up phone calls. Participation is fully voluntary, and participants may withdraw at any time. Participants will be randomized into either a high-dose vitamin D treatment group or a control group. Participants in both groups may continue all other cancer treatments including chemotherapy. Treatment group: Participants in the treatment group receive daily oral high dose Vitamin D supplementation provided free of charge through the clinical study. They also receive daily calcium supplementation 1000mg daily as per guidelines, provided free through the clinical study. Participants will have monthly blood and urine tests for monitoring purposes. All laboratory tests are free of charge. Participants also need to be available for a 15-minute phone consultation with a study coordinator every 2 months. Control group: Participants in the control group will continue their usual amount of Vitamin D and/or calcium if they wish to do so. No supplements will be provided through the study. Participants will be asked to provide a small blood and urine sample at the beginning of the study, every 8 months and at the end of the study. These blood and urine tests will be free of charge. Contact person: If you have any further questions regarding this study or you are interested in participating in this study, please contact us: British Columbia: 604-734-7125, toll free 1- 888-734-7125 or vitDstudy@inspirehealth.ca Ontario: 613-792-1222, toll free 1-855-546-1244 or email@example.com
- SUNSHINE Trial: high-dose vitamin D may benefit patients with metastatic colorectal cancer (Nov. 1/19)
Findings from a small clinical trial suggest that supplementing chemotherapy with high doses of vitamin D may be beneficial to patients with metastatic colorectal cancer (mCRC) by delaying the progression of the disease. Vitamin D is necessary for bone health and is made in the body through a chemical reaction that depends on sun exposure and intake of some fortified foods. In lab studies, vitamin D has shown anti-cancer properties such as triggered programmed cell death, inhibiting cancer cell growth, and reducing metastasis. While previous studies have linked higher blood levels of vitamin D with a lower risk of CRC and improved survival of patients, they were unable to prove that vitamin D was the direct cause.
In the SUNSHINE trial, 139 patients were recruited across the United States. All patients received standard chemotherapy (mFOLFOX6 plus bevacizumab). Patients were then randomly assigned to one of two treatment groups. Patients in the high-dose vitamin D group initially took 8,000 international units (IU) a day for 14 days, then 4,000 IU a day thereafter. Patients in the low or standard-dose vitamin D group took 400IU daily during all cycles. In the high-dose group, median progression-free survival (PFS) was 13. vs. 11 months in the standard dose group. Patients in the high-dose group were 36% less likely to have disease progression or death during the follow-up period of 22.9 months. No significant differences were found between the high-dose and standard-dose group in terms of tumour overall response rate or overall survival. Blood samples from participants were taken to measure the change in the levels of vitamin D before and after treatment. The test demonstrated that only 9% of the patients in the clinical trial had sufficient vitamin D at the beginning of treatment. Over the course of the study, patients in the high-dose group reached and maintained the vitamin D-sufficient range, while patients in the low-dose group had no substantial change in their vitamin D levels. The researchers found that the benefits of a high-dose vitamin D appeared to be less among obese patients and among those with tumours which contained a mutated KRAS gene, suggesting that certain subsets of CRC patients may need even higher doses of vitamin D for anti-tumour activity. High doses of vitamin D should not be taken except within the context of a clinical trial and under the supervision of specialists. The most common grade 3 and higher adverse events for chemotherapy plus high-dose vs. standard-dose vitamin D were neutropenia (35% vs. 31%) and hypertension (13% vs. 16%). The researchers conclude that the SUNSHINE trial findings are “extremely important” as they point to a cost-effective, safe, and easily accessible agent as a potential new treatment for mCRC.
- Study Looking for Female Survivors to participate in an Exercise Program (Nov. 16/19)
Researchers from the University of Toronto are performing a study investigating how female cancer survivors feel during and after different types of exercise. If you are a woman diagnosed with cancer and:
- Are 18-75 years old
- Completed treatment within 5 years
- Not exercising regularly
You can help! Study includes: three sessions over the course of 1.5 weeks consisting of a variety of exercises for 20 minutes (with breaks). You will be compensated $20 for participation in each session for a total of $60.
Please contact Allyson for more information: 416-946-5856 or firstname.lastname@example.org
21. Low-Dose Fish Oil No Help in Cutting Adenoma Risk, But African Americans And Those With Low Plasma Omega-3 Levels Might Benefit (Nov. 21/19)
A recent study conducted out of Harvard focussed on the anti-cancer effects of Marine Omega-3 fatty acids. It revealed that daily supplementation with Marine Omega-3 fatty acids (fish oil capsules) did not correlate across the board with a lower risk of conventional or advanced adenomas. Also, the study revealed that Marine Omega-3 supplementation did not affect a lower risk of high-risk serrated polyps, or other polyp subgroups (by size, location, multiplicity, or histology). In secondary analyses, Marine Omega-3 regimens did correlate a lower risk of conventional adenomas with low plasma Omega-3 at baseline. They also provided a beneficial association with the trial’s African American participants. Researchers concluded that this novel data on fish oil supplementation on early colorectal cancer could have implications for further studies.