Although the standard-of-care treatment for patients with metastatic pancreatic cancer remains largely unchanged with multi-agent chemotherapy, the role for multidisciplinary care has expanded significantly in recent years.
Although the standard-of-care treatment for patients with metastatic pancreatic cancer remains largely unchanged with multi-agent chemotherapy, the role for multidisciplinary care has expanded significantly in recent years, said Andrew E. Hendifar, MD, who added that such an approach to treatment can improve quality of life, alleviate cancer-related complications, and lead to the discovery of relevant genetic predispositions.
“The treatment of [patients with] advanced pancreas cancer, fortunately, is very straightforward. We’ve made some progress; however, when we use multi-agent chemotherapy regimens, some people feel that [we haven’t made] that much progress,” said Hendifar.
“It takes a village to take care of patients with pancreatic cancer; we need medical oncologists, palliative care physicians, dietitians, and genetic counselors involved. That [multidisciplinary] care extends to multiple facets [including] the cancer itself to associated complications, such as diabetes, pain, and weight loss,” Hendifar added.
In an interview with OncLive® during an Institutional Perspectives in Cancer webinar on gastrointestinal malignancies, Hendifar, medical director of Pancreatic Cancer and an assistant professor of medicine at the Samuel Oschin Cancer Center at Cedars-Sinai, discussed considerations for selecting frontline treatment in pancreatic cancer, the growing role of biomarker-driven therapies, and the importance of multidisciplinary care.
Hendifar: The easiest scenario is in the adjuvant setting where FOLFIRINOX has demonstrated superiority to single-agent gemcitabine. In patients who have completed definitive surgery and are medical candidates for FOLFIRINOX, [FOLFIRINOX] would definitely be the way to go. If patients are not medical candidates [for FOLFIRINOX], we have many options.
Choosing between the 2 regimens shouldn’t cause somebody too much grief or consternation because we just don’t have the data to know whether one regimen is superior to the other. When you have a gemcitabine-based or 5-fluorouracil [5-FU]–based first-line regimen, the second-line regimen will be the [alternative].
A lot of times in the clinic, I will discuss the available data and the pros and cons of each regimen with the patient so that we can make the decision together. [I’m] often surprised by how important it is for some patients to not have a port placed or how a continuous infusion is not feasible for some patients based on their social situation.
I try not to get too focused on which regimen we start first. In certain patient subtypes, including the BRCA-mutant population, we have the same questions about whether we should give gemcitabine plus cisplatin, or FOLFIRINOX.
Fortunately, several clinical trials [are ongoing] to definitively answer that question. One [study] is looking at nanoliposomal irinotecan [nal-IRI], 5-FU and oxaliplatin vs gemcitabine and nab-paclitaxel. The other [study is called] Precision Promise [NCT04229004] and is looking at modified FOLFIRINOX vs gemcitabine plus nab-paclitaxel. Therefore, we have 2 registration clinical trials [ongoing] that will be able to answer that question [of which regimen should be sequenced first].
My guess is that there won’t be much of a long-term survival difference between the 2 [regimens]. We may see a progression-free survival change, but once we switch to a second-line regimen, I can’t imagine it would make a difference.
NAPOLI-1 firmly places 5-FU plus nal-IRI as the optimal choice for second-line therapy in patients who have received gemcitabine as first-line treatment.
NAPOLI-3 is a registration trial comparing the frontline combination of 5-FU plus nal-IRI and oxaliplatin vs gemcitabine and nab-paclitaxel. This trial is very interesting because it [utilizes] modified oxaliplatin, and the nal-IRI dose has been modified. This is a regimen we would feel very comfortable using in the clinic and is kind of the way we actually manage patients [in this population]. In that sense, it is a very timely trial. It could possibly change the way that we treat patients with pancreatic cancer if [the data] show an improvement with the triplet therapy vs the doublet therapy in terms of survival, as well as tolerability.
As we understand the role of multi-agent first- and second-line treatments, we are also trying to understand the perioperative setting. What is the optimal [perioperative] approach with the current tools available? We are trying to better understand different subgroups of patients and biomarker-related subgroups, such as the DNA damage repair deficient [population], to better understand what we should do.
We are trying to better understand [other populations], such as the BRAF-mutant and KRAS-mutant groups. Finding those 1 in 100 alterations that are not KRAS mutations [is an ongoing challenge, but], that KRAS wild-type [population] is a very interesting group of patients to look at.
As far as KRAS mutations go, of course, KRAS inhibitors are on the rise. We have one KRAS inhibitor that is [close to being] approved and there are several in development. Unfortunately, KRAS G12C is a very rare mutation in pancreatic cancer, but KRAS G12D is very common. There are treatments being developed [specifically for KRAS G12D mutations]. We are trying to find the right KRAS-directed therapy for these patients.
In the meantime, treatments targeting tumor metabolism is something that should be looked at. We have several in development, including devimistat [CPI-613]. [Pancreas cancer tumors] seem to cause so much weight loss and muscle mass loss, so it makes sense that a treatment targeting tumor metabolism could be the way forward.
It is well known that KRAS mutations have specific effects on tumor metabolism, specifically regarding the tricarboxylic acid cycle [TCA]. Any therapy that targets TCA cycle metabolism makes a lot of sense to [evaluate] and pancreatic cancer is the perfect test-case for the principle behind this medication. We are very excited about the clinical trial [evaluating this approach] that has completed, and we are eagerly awaiting the results.
Therapies for pancreatic cancer are typically intense, multi-agent chemotherapies. They can cause problems such as weight loss, fatigue, and deconditioning, which are inherent in that patient population already. It’s essential that we jump on [supportive care measures, including getting dietitians involved, supplementing pancreatic enzymes, managing pain in effective ways, and using anti-inflammatory agents.
From our understanding, anti-inflammatory agents play a big role in cancer-associated inflammation and cachexia. Also, getting physical therapy involved to get our patients less deconditioned if possible is difficult, but we have to do that in order for patients to be able to receive systemic therapy.
When we are treating patients with pancreatic cancer, that is the time to rally the troops as much as possible. We want to get everyone involved because this patient group needs help and support [from a multidisciplinary team. Beyond] the medical oncologist, nurses can help explain to patients how to handle their treatments, dietitians can help them with weight loss, and palliative care doctors can help with pain. It may also be appropriate to get genetic counselors involved to make sure patients do not have any predispositions.
It seems like a lot of work, and it is. However, it is what we need to do right now for this patient group until therapies [improve]. One day in the future, I know we are going to say, “Wow, pancreatic cancer is easy [to treat]; we just give this medication, and everything is going to get better.” However, until that happens, the morbidity associated with this disease is immense, so we really need to rally the troops to get everybody together and help our patients.