Clinical Trial Landscape for Pancreatic Cancer

Pancreatic cancer led to 6.9% of all cancer-related deaths despite making up 2.8% of all new cancer cases reported in Australia in 2021. This is because it has a dismal prognosis. At the time of diagnosis, 50% of patients have metastatic illness. The 5-year survival rate for pancreatic cancer from the years 2013 to 2017 was 11.5%, ranking among the lowest of all malignancies and only slightly higher than the rate of 10.7% in the years 2012 to 2016. A significant symptom burden is also experienced by patients during their cancer treatment, which increases worry, depression, and poor quality of life. The National Pancreatic Cancer Roadmap was created by the Australian Government in response to the effects of pancreatic cancer and the urgent need to improve outcomes. Reviewing pancreatic cancer clinical trials to identify gaps and opportunities in the present clinical trials landscape across the pancreatic cancer care continuum was a crucial activity in assisting the roadmap’s core focus areas. We analyze the landscape of clinical trials along the pancreatic cancer care continuum in this viewpoint essay, with a focus on potential sites for upcoming trials.

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Clinical Trials for all Stages of Pancreatic Cancer

At least one Australian investigational location hosted 136 pancreatic cancer clinical trials between 1 January 2012 and 31 December 2020 (excluding studies solely devoted to pancreatic neuroendocrine tumors). Of these, 96 (71%) were clinical trials financed by industry, while 40 (29%) were investigator-initiated trials. 25 (63%) of the 40 investigator-initiated trials only enrolled individuals with pancreatic cancer (i.e., focused exclusively on pancreatic cancer). 28 (29%) of the 96 industry-sponsored trials were dedicated to pancreatic cancer.

One strategy is to map the interventions along the stages of the Optimal Care Pathway (OCP) 6, to comprehend the primary areas of emphasis of clinical trials. These steps are:

1. Early detection and prevention,
2. Presentation, initial investigations, and referral,
3. Diagnosis, staging, and treatment planning,
4. Treatment (for non-metastatic disease),
5. Care following initial treatment and recovery,
6. Management of recurrent, residual, or metastatic disease,
7. End-of-life care, as well as care that should be offered across the care continuum, including supportive and palliative care.

A significant portion of the pancreatic cancer investigator-initiated trials (25 trials) examined interventions along the OCP’s earlier stages, such as diagnosis, staging, and treatment planning (9/25, 36%) as well as non-metastatic disease treatments (10/25, 40%), particularly chemotherapy and/or radiotherapy for localized disease. The opposite pattern was shown in pancreatic cancer industry-sponsored trials (28 trials), which mostly looked at treatment for recurring, residual, or metastatic disease (23/28, 82%). None of the listed trials that were only concerned with pancreatic cancer examined end-of-life care, presentation, initial investigations, early detection, or prevention. Additionally, only a small percentage of investigator-initiated trials (2/25, 8%) examined supportive care-related therapies.

Contrarily, more investigator-initiated studies were done in other diseases, such as pancreatic cancer (15 trials), where early diagnosis (1/15, 7%), pharmacogenetics (1/15, 7%), rehabilitation (2/15, 13%), emerging treatments (1/15, 7%), and supportive care (5/15, 33%) were all investigated. Targeted treatments (20/68, 29%) and immunotherapies (16/68, 24%) in non-metastatic illness were given more attention in industry-sponsored studies undertaken in other diseases, such as pancreatic cancer (68 trials). It is unknown, though, what percentage of the total sample in these studies would be made up of participants who had pancreatic cancer.

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Pancreatic Cancer Clinical Trials are Hard to Access

In the pancreatic cancer studies, only four (16%) of the investigator-initiated trials (10/25, 40%) recruited patients from outside the country. On the other hand, 26/29, or 93% of industry-sponsored studies, enrolled participants from outside. In urban areas in Victoria, New South Wales, and South Australia, trials primarily recruited participants. Unfortunately, there were no Northern Territory recruits in any of the listed pancreatic cancer trials. Trials also did not include information about the deliberate inclusion of Indigenous peoples or other underrepresented groups. Similar patterns were seen in trials for several diseases, such as pancreatic cancer.

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Pancreatic Cancer Priority Regions

Few clinical trials were found in the fields of prevention or early detection, first investigations and referral, or end-of-life and supportive care, even though delayed diagnosis, poor survival, and a high symptom load are well-known problems in pancreatic cancer. The question of "how can patients with pancreatic cancer be offered a holistic treatment package (e.g., survival time, quality of life, mobility, autonomy, among others)?" was recognized by the Priority Setting Partnership for Pancreatic Cancer. The small number of trials found in the fields of palliative and supportive care points to a substantial gap in our research agenda. " as one of its top ten research priorities.

The 5-year survival rate for pancreatic cancer has marginally improved over time, suggesting that urgent research into novel therapeutic strategies is required. According to our analysis, targeted medicines were mostly studied through clinical trials that enrolled participants with a variety of cancer types. However, it was difficult to tell from the majority of trial registration records whether the percentage of participants were pancreatic cancer patients who had access to cutting-edge treatment options.

Reasons for Lack of Clinical Trials in all Stages of Pancreatic Cancer Treatment

The restricted number of pancreatic cancer trials presumably has many causes. The low number of supportive care studies in this demographic may be explained by the palliative care setting's frequent difficulties with participant recruitment and high attrition rates brought on by participants' rapid declines. Variations in funding across the cancer care continuum may also be responsible for a paucity of clinical studies across the OCP, which may call for tailored requests for funding.

Opportunities to Increase the Scope of Pancreatic Cancer Clinical Trials

According to a prospective study carried out by Cancer Australia in July 2015, the percentage of funds committed to pancreatic cancer research in Australia was low compared to the disease's mortality and impact. Targeted financing may assist address the low 5-year survival rate seen in pancreatic cancer given that clinical trials offer chances for advancements in the early diagnosis and treatment of tumors. Future clinical trials should think about looking into crucial pancreatic cancer care continuum interventions that have been overlooked thus far, like early diagnosis or prevention, first investigations and referrals, novel therapeutics, and end-of-life and supportive care-related interventions.

There is a compelling case to be made for the exploration of early detection measures, although there are several risk factors for pancreatic cancer and no one prevention strategy. Advances in imaging and/or ‘omics’ to find potential biomarkers, along with big data analytics to identify who would benefit from more effective surveillance programs, may be used to develop novel strategies for early detection.

Recruitment and retention issues frequently pose a barrier to supportive and palliative care trials in cancer populations with low survival rates. Increased participation in this set of research may be made possible by carefully planned treatments that allow for flexibility and do not demand time-consuming and onerous patient assessment methods. Studies looking into supportive and palliative care or early detection methods might be observational and hence not be recorded. Therefore, there is room for additional studies to examine the state of observational studies in pancreatic cancer in the future.

Increased efforts to improve the quality of life and survival of patients with this type of cancer may be sparked by more national and international cooperative clinical trial programs created by clinical investigators, like the MoSTP trial which stratifies patients with pancreatic cancer by their biomarkers to receive the most promising targeted therapy. Coordination and leadership from all interested stakeholders can help to overcome the many obstacles that collaborative clinical trials frequently face, such as complicated regulatory and ethics review requirements, high costs, and logistical problems.

It seems that different parts of Australia had unequal access to clinical trials. Regional and distant participants may have more access to clinical trials thanks to the growing field of tele-trials. Additionally, compared to non-Indigenous Australians, Indigenous Australians have much higher age-standardized incidence and mortality rates of pancreatic cancer, which emphasizes the need for focused recruitment of underrepresented populations. To better understand the current challenges associated with conducting clinical trials in the pancreatic cancer population and to identify opportunities for greater participation, qualitative investigations with pertinent stakeholders that make sure they capture the diversity of the Australian population may be helpful. By including consumers early in the clinical trial design process, access, recruitment, and retention hurdles may be further reduced.

Source-Medindia