ASCO 2017: Case Study - The Impact of Early Diagnosis

The Impact of Early Diagnosis

Case Study: A 62-year-old man presented with a 4-month history of fatigue, vague abdominal discomfort and a 30 lbs unintentional weight loss.  His past history was significant for ethanol abuse, hypertension, high cholesterol and type 2 diabetes and his medications included hydrochlorothiazide, rosuvastatin, metformin and ramipril.  Bloodwork including CBC, lytes, creatinine and LFTs were all normal. U/S of the abdomen revealed a nonspecific gas pattern with no obvious significant abnormalities.  Due to persistent symptoms, a CT abd/pelvis was arranged that identified subtle soft tissue changes in the region of the celiac axis.  An MRI was performed to specifically evaluate the pancreas which confirmed a primary pancreatic lesion that might represent the sequelae of chronic inflammation although pancreatic cancer couldn’t be excluded.  CA 19-9 was 87.  He was referred to gastroenterology who performed upper and lower endoscopy and took brushings and washings of the pancreatic duct.  All results were either insufficient for interpretation or negative for malignancy.  His case was discussed at a GI multidisciplinary case conference and it was felt that the lesion could be consistent with a pancreatic cancer and that due to the presence of vessel involvement, would not be a surgical candidate.  It was also deemed that the lesion could not be safely biopsied percutaneously and so he was referred for an endoscopic ultrasound and biopsy for diagnosis.  This was ultimately performed but the sample demonstrated very little cellular material with some inflammatory cells and signs of atypia but no confirmation of adenocarcinoma or malignancy.  During this time, his weight loss continued and his pain worsened. 

Discussion: Pancreatic cancer continues to be a challenging tumour site.  Early diagnosis is key to management as the only curative strategy involves surgical resection of the primary tumour.  However, patients often have very few symptoms or have those that mimic more common, less dangerous conditions thus leading to a potential delay in the time to appropriate investigations and diagnosis.  At present, there are no screening programs for pancreatic cancer due to the relatively low prevalence of the disease, challenging imaging characteristics and lack of a reliable identifiable biomarker. 

As highlighted by the case example, making a diagnosis can be very challenging as patients often present with nonspecific symptoms and are already at a point where the disease has become too advanced for surgery.  Imaging tests may not be able to reliably distinguish between chronic pancreatitis and malignancy and although the CA 19-9 is sometimes helpful, it can be elevated for both benign and malignant reasons and may even be normal in the setting of malignancy.  Acquiring appropriate tissue sampling is also often a challenge particularly in the locally advanced setting as the primary site may be difficult to access for biopsy.  This may lead to repeated attempts at biopsy and a delay in initiating treatment.

Patients with advanced disease are often managed in multidisciplinary settings with supportive care and palliative care forming a significant element of co-managed care from the outset.  For motivated patients with good PS, multi-agent chemotherapy with FOLFIRINOX or Gemcitabine and nab-paclitaxel or enrollment on clinical trials if available are good options for initial therapy.  Single agent gemcitabine still remains an option for some patients or those with poorer PS. While newer therapies such as the immuno-oncology agents have yet to show significant benefit, other agents that attempt to improve drug delivery and/or drug penetration into the tumour are showing promise.  Examples include nanoliposomal irinotecan and PEGPH20.  In addition, there is evidence from retrospective series now showing that effective use of first-line treatment leads to a greater likelihood of receiving second line therapy and a longer overall duration of treatment with improved OS.  This highlights the importance of careful patient selection and treatment individualization to maximize outcomes. 

Insights provided by: 
Dr. Robert El-Maraghi, MD, FRCPC
Simcoe Muskoka Regional Cancer Centre

GICS 2017: News in Colorectal Cancer

GICS 2017. Abstract 519: Nivolumab alone or in combination with ipilimumab in patients with DNA mismatch repair deficient/ microsatellite instability high metastatic colorectal cancer: Updated results from CheckMate 142.

Michael J. Overman et al.

Results: Among pts treated with nivo 3 Q2W (N = 74), 84% had received ≥ 2 prior lines of therapy. ORRs were 31% (INV) and 27% (IRRC); disease control rates were 69% (INV) and 62% (IRRC). The median time to response was ≈2.7 mo (INV/IRRC). PFS rates at 12 mo were 48.4% (INV) and 45.6% (IRRC). The duration of response and OS medians were not yet reached; OS rates were 83.4% (6 mo) and 73.8% (12 mo). Responses were observed in pts regardless of tumour programmed death-1 ligand 1 (PD-L1) expression level or BRAF or KRAS mutation status and were observed in pts with or without a history of Lynch syndrome (Table). Grade 3–4 treatment-related adverse events (TRAEs) occurred in 20% of pts. TRAEs leading to discontinuation included acute kidney injury, increased ALT, colitis, and stomatitis (1 each). No treatment-related deaths occurred in this arm.

Conclusions: Nivo showed durable responses and disease control in heavily pretreated pts with dMMR/MSI-H mCRC. Treatment was well tolerated, with no new safety signals. Clinical trial information: NCT02060188

 

GICS 2017: News in Pancreatic Cancer

GICS 2017. Abstract 303: Efficacy and safety of liposomal irinotecan (nal-IRI) + 5-fluorouracil and leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) who previously received gemcitabine (gem)-based therapy: Post-hoc analysis of the NAPOLI-1 trial

Li-Tzong Chen et al.

Results: Of 117 pts in the nal-IRI+5-FU/LV arm, 53 (45%) previously received gem monotherapy and 64 (55%) previously received gem combo including erlotinib (n = 9) or nab-paclitaxel (n = 20). Of the 119 pts in the 5-FU/LV arm, 55 (46%) previously received gem monotherapy and 64 (54%) previously received gem combo including erlotinib (n = 17) or nab-paclitaxel (n = 11). Nal-IRI+5-FU/LV improved median OS, median PFS, and ORR vs 5-FU/LV, regardless of prior therapy (Table). Grade ≥3 treatment-emergent adverse events were not influenced by prior treatment. Clinical trial information: NCT01494506

Conclusions: These results show consistent benefit of nal-IRI+5-FU/LV treatment across subgroups of pts who previously received gem therapy and support the ASCO guidelines recommending nal-IRI+5-FU/LV for this pt population. These analyses may be limited by the small sample size of treatment arms.

CARE FACULTY PERSPECTIVE: Gemcitabine containing regimens, either as a single agent or in combination with nab-paclitaxel remain appropriate treatment options in Canada for first line treatment of patients with pancreatic cancer. In particular, combination therapy has demonstrated improved overall survival and QoL in appropriately selected patients resulting in its adoption as one of the gold-standard therapies for first line treatment.i Moreover, it appears that first line treatment with a gemcitabine containing combination regimen may also be a predictor of receiving second line therapy thus potentially leading to improved outcomes.ii However, despite the recent advances in the management of advanced cancers, patients with pancreatic cancer continue to have relatively few therapeutic options in the second line setting and have generally poor outcomes. This type of data is certainly encouraging and demonstrates that the addition of liposomal irinotecan to infusional 5FU/LV improves both PFS and OS vs 5FU/LV alone. It should be noted however, that the comparator chemotherapy arm was not our typical standard and was different from that used in the experimental arm. In addition, given the population at hand, it would have been ideal to have a group managed with palliative care alone to further highlight the likelihood of treatment effect. This trial highlighted the importance of first line therapy in the probability of receiving second line therapy and thus achieving an OS benefit. It will be interesting to see how payers will interpret this data given that in Ontario, the non-liposomal irinotecan-containing regimen FOLFIRI is not considered evidenced-informed for this indication and is not yet reimbursed.

Click here to read the full report from GICS 2017.

Press Release: CARE Congress on Biosimilars

On January 13th, 2017 CARE faculty specialists representing the fields of gastroenterology, hematology, oncology, respirology and rheumatology met to consider the integration of Biosimilars into the Canadian healthcare system.

Biosimilars are drugs that may replace expensive biologic drugs that are going off patent.  With biosimilars being relatively new to the Canadian landscape, there are also a number of questions/considerations on extrapolating data, interchangeability, immunogenicity, and systemic challenges (tracking and monitoring) that require attention.

Recognizing both the potential impact on the Canadian healthcare system and the importance of involving stakeholders, CARE faculty invited 16 speakers representing Canadian researchers, clinicians, Health Canada, public and private funding agencies, health economists, hospital pharmacists, nurses, advocacy groups, ethicists and legal experts to share perspectives, concerns, wants and needs.

An audience of 100+, representing the above named stakeholders, along with various levels of government, pharmaceutical companies and industry associations, listened in while speakers and assembled faculty discussed biosimilars from multiple perspectives.

The aim of this Congress is to increase collective understanding, consider education needs for specialists and assembled stakeholders, and ultimately refine a CARE guidance/position on Biosimilars.

 

CARE Faculty believes: 

  • Developing clinical practice through optimization of current therapies
  • Improving patient outcomes by developing innovative therapeutics
  • Ensuring access to quality care for all Canadians by the responsible and evidence-based use of treatment
  • Competition is welcomed to improve efficiency and access

 

CARE™ funding sources:

CARE™ receives unrestricted funding from multi-industry sponsors, institutions and associations. Content reflects the opinions, presentations and analyses of experts, investigators, educators and clinicians ("CARE Faculty"), whose activities, while independent, are commercially supported by the noted sponsor(s). Program content is developed independently of sponsor(s).

 

Background Steps that led up to this CARE™ Congress

  • CARE™ conducted needs assessments in oncology, hematology, rheumatology, and gastroenterology to understand current perceptions of biosimilars and their use in Canada
  • A multi-disciplinary group of CARE faculty members met October 27th, 2016 to discuss the various needs assessment data, and the impact biosimilars will have in Canada
  • There was consensus to host a larger meeting involving more stakeholders; CARE™ has worked to quickly assemble this Congress involving not only different specialties, but different stakeholder representatives.

For more information on the steering faculty, assembled CARE faculty, speaker list, or for questions/information needs regarding CARE, please contact Christina Lopes or Erica Duncan. 

 


References:

  1. Hirsch BR, Lyman GH. Biosimilars: are they ready for primetime in the United States? J Natl Compr Canc Netw. 2011;9: 934–943
  2. Based on 2013 sales of biologics with patents expiring before 2021 (Remicade, Eprex, Aranesp, Levemir, Humira, Avastin, Enbrel, Lucentis, Rituxan, Gonal-F). IMS Health Canada - Canadian Drug and Hospital (CDH) Sales, December 2013, page 11

Click here to view more highlights from the CARE Congress on Biosimilars.

Insights on the NOR-SWITCH trial are now available! Hear from Canadian experts Drs. Brian Feagan & John Marshall

Biologic therapy has revolutionized the treatment of IBD and improved patient outcomes drastically. Many of the biologic therapies we routinely use are now or soon going off patent and competitive molecules, subsequent entry biologics (SEBs), are now being introduced. SEBs have potential implications for our own practices but also for how we manage our pharmacy budgets and how we deliver health care in Canada.

The NOR-SWITCH trial was a randomized, open-label trial studying a cohort of patients who were stable or in remission on the innovator biologic, infliximab (REMICADE®). Patients were randomized to either continue with infliximab or switch to a SEB version of infliximab (INFLECTRA® in Canada). This was a cross specialty trial that included patients from a variety of diagnoses, including: rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, UC, CD and chronic plaque psoriasis. Each group was followed for different endpoints over the course of the trial.

CARE Gastroenterology Faculty lead, John Marshall (McMaster University), sat down with Dr. Brian Feagan (Professor of Medicine at the University of Western) to critically assess this study and discuss how the results should be interpreted and applied in Canadian practice.

 

Interested in learning more? Join us at The CARE Congress on Biosimilars!

CARE Update: Fall 2016

 

CARE (Community, Academic, Research, Education) develops a number of educational initiatives throughout the year, designed to educate Canadian specialists on the latest news and developments in their respective fields, reflecting a national outlook but also recognizing regional considerations.

The CARE Faculty is comprised of leading Canadian specialists in a number of different disease categories, including (but not limited to): Gastroenterology, Rheumatology, Hematology, Oncology.

The CARE Faculty is excited to announce a number of new developments that have taken place so far this year. What follows is an update on the programs the CARE Faculty has developed in the last quarter of 2016, as well as upcoming CARE events.

 
 
 
 
 
 
 
 
 
 
 
 
 

ASCO GICS 2016. Abstract 31

ASCO GICS 2016. Abstract 315.  Efficacy and safety of everolimus in advanced, progressive, non-functional neuroendocrine tumours (NET) of the gastrointestinal (GI) tract and unknown primary: A subgroup analysis of the phase III RADIANT-4 trial.

Simron Singh et al.

Results: Of 302 pts, 175 had GI NET (EVE [n=118], PBO [n=57]); 36 had NET of unknown primary (EVE [23], PBO [13]). In GI NET pts, median age was 63 y; females: 55%; G1/G2: 75%/25%; WHO PS: 0, 78% or 1, 22%; Caucasian: 73%. Similar baseline characteristics were observed in pts with NET of unknown primary. Ileum (41%), rectum (23%) and jejunum (13%) were the most common locations in GI subgroup. In pts with GI NET, median PFS (95% CI) by central review (EVE vs PBO) was 13.1 (9.2-17.3) mo vs 5.4 (3.6-9.3) mo with an estimated 44% risk-reduction in favor of EVE (HR, 0.56; 95% CI, 0.37-0.84). In pts with NET of unknown primary, median PFS (95% CI) by central review (EVE vs PBO) was 13.6 (4.1-not evaluable) mo vs 7.5 (1.9-18.5) mo (HR, 0.60; 95% CI, 0.24-1.51). The most frequent G3/4 adverse events irrespective of drug-relationship reported in ≥5% pts in GI subgroup were diarrhea, hypertension, stomatitis, abdominal pain, fatigue, and acute renal failure. 

Conclusions: The present subgroup analysis of RADIANT-4 study demonstrated improvement in PFS with EVE for pts with GI NET, and suggests efficacy in NET of unknown primary, with an estimated 40% to 44% risk-reduction in favour of EVE vs PBO. Safety profile for EVE is consistent with that previously reported. Clinical trial information: NCT01524783

CARE Faculty Perspective: The RADIANT4 trial examined everolimus, an mTOR inhibitor, versus placebo for patients who have advanced, progressive, non-functional neuroendocrine tumours of the GI tract and unknown primary. This analysis affirms a significant PFS benefit with everolimus in the GI and unknown primary NET subgroups.