The treatment landscape for advanced pancreatic cancer has expanded in recent years, but it continues to be a very complex and devastating disease.
BY Lauren M. Green
Although the treatment landscape for advanced pancreatic cancer has expanded in recent years, this diagnosis remains one of the most devastating for patients and their loved ones.
More than 50 percent of patients with pancreatic cancer are diagnosed at a later stage. These patients and their caregivers need support in selecting therapies that balance their desire for the best possible outcome with concerns about maintaining a good quality of life. Knowing when to initiate end-of-life planning discussions poses yet another challenge for clinicians who can expect to see more patients with this diagnosis in the years to come.
Currently, pancreatic cancer is the fourth leading cause of cancer death in the United States, and by 2030, the disease is forecast to become the second leading cause of cancer-related death.
Given the intensive supportive care needs of patients with late-stage pancreatic cancer, it’s not surprising that Nina N. Grenon described these patients as “a nursing population.” “They have so many needs—physical, psychological, spiritual, and existential—that nurses can attend to … this is what nurses do best,” said Grenon, a nurse practitioner at the Dana- Farber Cancer Institute in Boston who has been practicing in the pancreatic cancer setting for more than 18 years.
The multifaceted and complex needs of patients with pancreatic cancer stem, certainly in part, from the fact that less than 20 percent of cases are truly localized to the pancreas, where the cure rate is highest.
For a patient to be cured of pancreatic cancer, radical resection is the only option, explained Philip A. Philip. Unfortunately, when a good resection is achieved with negative margins, the majority of patients will experience recurrence due to the presence of micrometastatic disease, even in patients where the disease is believed to be localized, continued Philip, a specialist in gastrointestinal oncology at the Karmanos Cancer Center in Detroit.
“Over the past decade, we have learned more about this disease than we had at any time before,” but, he added, “this is a very complex disease,” and improving outcomes will require better systemic treatments.
“We don’t really have a defined genetic abnormality that we think is driving the tumor, except for KRAS mutations, which are predominant in 90 percent of patients … at this point in time, we have not been successful in identifying drugs that are really good and specific to the KRAS pathway.”
Philip acknowledged that screening for pancreatic cancer also remains a challenge, due to a lack of screening tools and guidelines for identifying who to screen. Screening older individuals with newly diagnosed diabetes, for example, could generate a lot of false positives, creating more problems. “We don’t really have a good feel for who is the really high-risk individual in the community so that we can go after those patients and screen them.
“Having said that, there will be individuals who are at high risk because they have a family history of certain cancers, or they may be carrying a gene that predisposes them to pancreatic cancer,” Philip noted. These individuals represent a very small percentage of the population, however, and then there is the conundrum of how often they should be screened, he added.
Treatments and Side Effects
“The good news is, we have emerging options for the treatment of metastatic pancreatic cancer and now have the luxury of choice for some patients,” said Eileen M. O’Reilly, associate director for clinical research at Memorial Sloan Kettering’s David M. Rubenstein Center for Pancreatic Cancer Research in New York City.
O’Reilly pointed to the major trials which have defined the two current treatment standards in metastatic disease: (1) FOLFIRINOX (a regimen of leucovorin calcium, fluorouracil, irinotecan hydrochloride and oxaliplatin) and (2) nabpaclitaxel and Gemzar (gemcitabine).
The phase 2/3 PRODIGE study, conducted in France, looked at FOLFIRINOX compared with gemcitabine in patients with an ECOG performance status of 0-1. The median overall survival (OS) was 11.1 months in the FOLFIRINOX arm compared with 6.8 months for gemcitabine; corresponding improvements in progression-free survival and tumor response also were reported. FOLFIRINOX has inherent side effects, such as gastrointestinal toxicity, myelosuppression, infection, neuropathy, and fatigue. To compensate for these adverse events, this regimen is often modified to preserve efficacy while ameliorating toxicity, O’Reilly said, though most patients stop treatment because of disease progression, not toxicity.
The phase 3 MPACT study introduced the combination of Abraxane (nab-paclitaxel) and Gemzar for patients with advanced pancreatic cancer. In this trial, the median OS was 8.5 months with Abraxane plus Gemzar compared with 6.7 for Gemzar alone. A study reported at the 2015 Gastrointestinal Cancers Symposium in January found that less frequent dosing of the regimen reduced side effects without impacting efficacy. Philip noted that use of these two regimens is not limited to metastatic disease: “We can bring them in for earlier-stage disease such as locally advanced, unresectable, borderline resectable, and even resectable disease.”
O’Reilly said the two regimens are comparable in terms of efficacy, although there are some practical logistical issues, along with patient preferences as to why one approach might be preferable. Philip said that he routinely involves his patients in the decision making because they need to be aware of what is involved with each regimen.
The side effect profile for the Gemzar and Abraxane combination appears to be more favorable, he added, but he stressed that both regimens should be used with caution in patients with abnormal liver function tests.
“Sometimes we have to change treatment, not only because of tumor resistance, but also because the patient is not able to tolerate the therapy,” he added. He said this happens more with FOLFIRINOX due to gastrointestinal side effects.
The experts agree that whatever therapeutic regimen is deployed, patients will require intensive supportive care.
“Chiseling away” is the approach Grenon says works best in addressing the many needs of patients with a diagnosis of advanced pancreatic cancer. “When I see patients, I do just one topic at a time, starting with physical symptoms, especially pain.”
“Pain is something patients should not be experiencing,” concurred Philip. “We have to be very aggressive in how we control pain.” He added that patients also frequently experience weight loss, nutritional issues, and depression. It’s very important for the patient to be aware that treating the cancer is not only treating with chemotherapy, radiotherapy and/or surgery, but that there are a lot of supportive care elements which must be incorporated alongside their regular treatment.
The Promise of Clinical Trials
The approach to second-line therapy or for those who cannot tolerate the first regimen is typically to switch to whichever regimen hasn’t previously been given. The majority of patients will experience early progression of their disease, warranting further investigation of new therapies. Patients with a good performance status and organ function should be considered for a clinical trial.
Gemzar with Abraxane has been identified as a reference regimen for good performance status of patients with metastatic disease, O’Reilly noted, which provides a platform for integrating new agents. Phase 1b and randomized phase 2 trials are underway, adding novel agents to the combination. “It’s a little harder to do that with FOLFIRINOX, because of overlapping toxicities,” she added.
For patients interested in pursuing a clinical trial—which both oncologists agreed is especially important in this setting—the clinical trials database of the Pancreatic Cancer Advocacy Network (PanCAN
) is an excellent resource, they said. PanCAN also offers an array of patient support services through its PALS program.
“It’s an advantage for patients to go on a clinical trial,” says Philip, “because they will have the opportunity to be on a new drug in addition to what would be standard of care.”
Philip said that pancreatic cancer is a disease where it’s hard to justify starting the treatment the next day or even the next week. This diagnosis is a lot to take on for the newly diagnosed. “Patients have to have the opportunity to know and discuss their options. And if they really want to do a clinical trial, they have to have the opportunity to go see someone about the trial.”
For Carmela L. Hoefling, who has been practicing in this setting for 12 years, improving awareness and understanding of this disease among nurses is vital.
A nurse practitioner at the Rutgers Cancer Institute of New Jersey, Hoefling is presenting a poster at the Oncology Nursing Society annual meeting this month focused on building the knowledge base of nurses about prevention, the difficulty of early diagnosis, symptom management strategies, current treatments and clinical trials.
In addition to a family history of pancreatic cancer, there are modifiable risk factors such as obesity and smoking, the latter increasing an individual’s risk by 20 percent to 30 percent, she noted. “Nurses need to have a good knowledge base that will give them the tools to help educate the public,” says Hoefling, who would like to see informational sessions focused on pancreatic cancer provided to healthcare professionals delivered on site, as well as at local and national professional society meetings.
“Overall, I think healthcare providers have gotten better at recognizing what may be early warning signs, such as new-onset diabetes that can occur two to three years prior to diagnosis of pancreatic cancer. Also, unintentional weight loss—that’s a red flag that many patients experience for almost a year up to diagnosis,” Hoefling explained.
She also suggested web-based tools or videos, along with informational pamphlets, so that patients and providers can better recognize possible early symptoms of pancreatic cancer and also increase their awareness of lifestyle steps that can help to prevent it. In addition to not smoking, these include maintaining a healthy body weight and limiting alcohol intake.
Hoefling hopes that her project will provide nurses with strategies to help relieve symptoms such as pain, depression and fatigue that are related to both the disease and its treatment.
“Studies have shown that complementary therapies such as art, music, acupuncture, and meditation, as well as exercise and yoga, have a multitude of benefits,” Hoefling says. “We know that the benefits are not only physical, but psychological as well. When you use these approaches, they help patients decrease their fatigue, which increases their energy level and decreases their stress and anxiety.”
Early Palliative Care
“The patient with pancreatic cancer has so many needs which nurses can attend to,” stressed Grenon, who presented two research studies focusing on the importance of early palliative care for patients with pancreatic cancer at the American Society of Clinical Oncology’s inaugural Palliative Care in Oncology Symposium last fall.
Her research builds on earlier published studies suggesting that early palliative care combined with standard care improves quality of life for patients with advanced cancer and potentially can extend survival.
Grenon noted that some of the barriers to providing early palliative care include a knowledge gap on the part of patients about what palliative care means, often confusing it with hospice. Another potential barrier is that oncologists and other providers may feel that they are already providing it.
Time is also a challenge. “These patients are highly symptomatic, and their symptoms predictably get worse over the course of their disease,” she says. “With some facets of palliative care, and specifically when you’re discussing advance directives, goals of care, end-of-life care … when you ask patients if they have thought about how they would like to live if they only have a limited time … that understandably takes a long time.”
Grenon and colleagues initiated a retrospective medical record review of 150 patients treated for pancreatic cancer at the Dana-Farber Cancer Institute between January 2009 and December 2011 and found that most palliative care discussions occurred late in the cancer care trajectory.
Mean length of care for these patients was 414 days; 52 records (35 percent) included documentation of a palliative care discussion, with most taking place at the time of disease progression. Prognosis discussions occurred after a mean of 177 days, and a palliative care consultation was conducted, on average, at day 343, with the majority of consultations (82 percent) requested to help the patient manage symptoms.
For the other quality improvement study, Grenon and colleagues conducted a retrospective chart review of patients diagnosed with pancreatic cancer at her institution and found that only 19 percent of patients had a documented educational conversation about pancreatic cancer within the first four weeks of care.
The researchers designed a quality improvement intervention involving a palliative care fact sheet for providers to share with patients; providers also received email reminders for all eligible patients with the information sheet attached to patient encounter forms to share with patients, preferably at the first visit if their staging workup and pathology review had been completed. Chart audits revealed that all patients were educated about palliative care within one month of establishing care as a new patient.
Without the email reminders, however, the patient education discussion only occurred for 50 percent of patients. Grenon said that as part of another project, the patient admission will be the trigger to initiate palliative care, using the fact sheet as a teaching point for all patients with metastatic disease, not just those with locally advanced and metastatic pancreatic cancer.
Grenon, like Hoefling, would like to see greater awareness as well as training for nurses focused on pancreatic cancer and on meeting the complex needs of patients with this diagnosis. Even some nurses still don’t understand the difference between palliative and hospice care, Grenon has found. She said that palliative care is similar to the care she delivered at the bedside 30 years ago as a staff nurse doing rounds with a pain and symptom management group: “That was palliative care.”
Last summer Grenon visited the United Kingdom and spent time observing the St. Christopher’s Hospice program, where she was struck by how well patients were supported by nurses in the community in managing pain and other symptoms.
“What impressed me the most about the way they delivered palliative care,” says Grenon, “is that these patients were never acutely hospitalized” and were referred to inpatient hospice only when acute treatment was needed—to treat a wound or infection, for example. Grenon said that at the heart of the organization is “a robust home care program” involving teams of specialist nurses, doctors, social workers, and welfare officers who help family caregivers support their loved ones.
Supporting the caregivers of patients with pancreatic cancer is especially important, says Grenon. She recalled the appreciation she received from the wife of a patient she treated 18 years ago with whom she has stayed in touch, for providing the palliative care that enabled her husband to be cared for at home: “You taught us how to give I.V. fluids, how to give electrolytes, how to take care of his pain, so he could be at home and not in the hospital. Maybe it wasn’t called palliative care at the time, but it’s the nursing care that you gave him.”
Patients and practitioners can be heartened by research into more effective pancreatic cancer treatments and developing a better understanding of the disease, so that biomarkers may be identified, and with that, screening tools. “New drugs are the future in this disease,” says O’Reilly. Several promising therapies are on the horizon for patients with advanced pancreatic cancer, including MM-398, immunotherapy, and targeted therapies. Philip noted that the NCI is currently funding an initiative focused on tumors that are KRAS-mutated. “Hopefully, that will be something good for pancreatic cancer in the coming years in terms of finding new treatments.”
“There’s room for improvement, and a lot more research is needed,” concluded Hoefling, “but there’s definitely hope.”
Pancreatic Cancer Advocacy Network, pancan.org
As a nationwide network dedicated to advance research, support patients, and create hope for those affected by pancreatic cancer, PanCAN maintains a searchable database of pancreatic cancer clinical trials for healthcare professionals and the general public. Interested individuals may also contact a trained Patient and Liaison Services (PALS) associate at 877-272-6226 or email email@example.com for guidance on clinical trial options. PanCAN resources also include disease-specific treatment information (through its Know Your Tumor personalized medicine service), advice on diet and nutrition, side effect management, and other support resources.
The National Pancreas Foundation, pancreasfoundation.org
Provides hope for those suffering from pancreatitis and pancreatic cancer through funding cutting-edge research, advocating for new and better therapies, and providing support and education for patients, caregivers, and healthcare professionals. The NPF website provides an array of supportive tools, including physician and patient interviews, disease tutorials, and information about diagnosis, treatment options, and nutrition.
The Lustgarten Foundation, lustgarten.org
Supports research into the biological mechanisms and clinical strategies related to the prevention, diagnosis, and treatment of pancreatic cancer, and facilitates enhanced dialogue among members of the medical and scientific communities about basic and clinical research. The organization also provides information and support services for patients and their families.
Hirshberg Foundation for Pancreatic Cancer Research, pancreatic.org
A national nonprofit organization dedicated to advancing pancreatic cancer research and providing information, resources, and support to pancreatic cancer patients and their families. The research mission of the foundation focuses on the physiology, early diagnosis, treatment, and prevention of pancreatic cancer.