Increasing representation of women in gastrointestinal (GI) oncology research is helping shape the direction of clinical investigation and treatment development, particularly in challenging diseases such as metastatic pancreatic cancer, according to Rachna T. Shroff, MD, MS, FASCO, who noted that a growing number of women are serving as investigators, trial leaders, and collaborators in studies centered on targeted therapy development.
This shift has coincided with the continued evolution of frontline treatment selection for metastatic pancreatic cancer, where oncologists now navigate multiple chemotherapy backbones when determining the optimal approach for individual patients.
“Having diversity in terms of women helping to write and run these trials has been wonderful to see, and we are seeing it more. The lead investigators on a lot of these targeted therapies for pancreatic cancer are women,” Shroff, the associate director of clinical investigations and coleader of the Gastrointestinal Clinical Research Team at the University of Arizona Comprehensive Cancer Center in Tucson, shared in an interview with OncLive®.
Beyond discussing how increased representation of women in clinical trial leadership is contributing to more diverse perspectives in trial design and translational research, Shroff also outlined the patient- and disease-specific factors that guide frontline chemotherapy selection in metastatic pancreatic cancer.
Shroff is also a professor with tenure in the Department of Medicine, chief of the Division of Hematology and Oncology for the University of Arizona College of Medicine—Tucson; and medical director for the Oncology Service Line with Banner Health.
OncLive: Over the course of your career, how have women become more engrained in the pancreatic cancer and GI oncology fields to help drive some of the pivotal research aiming to improve patient outcomes?
Shroff: It has been fun to watch what I believe is slowly but surely becoming a sea change in terms of empowering women in GI oncology. This is a bit of a passion project of mine that is really important to me, because I do believe that diversity in designing, writing, running, and presenting clinical trials leads to a diversity of ideas and a cross-pollination of how to move the needle forward.
I give kudos to the partnership between academic medical centers and industry for being intentional about bringing multiple and varied voices to the table as they think through how to design these trials, because it ensures the best and smartest trial designs.
For younger women breaking into the oncology field, what is the importance of mentorship in career development? How did mentorship help you, and how are you paying it forward?
The first thing I would say is to be patient. It takes time to know the disease well enough to have thoughtful [perspectives] when you have a seat at the table. One of my mentors told me that the first thing to do was learn how to take really good care of [patients with] pancreatic. By immersing yourself in the clinic, the research questions will come up, and you will know what questions to ask and bring forward.
It is also really important to be intentional, thoughtful, and have follow-through. If you are going to help design or open a clinical trial, be responsive and mindful of how to care for those patients. Learn from every single patient and bring that information back to the steering committee, to the industry partners, and to your academic colleagues to help us learn from each other. As we learn from each other, we learn how to take better care of patients. The last thing I would say is to pay it forward. That is what I am trying my best to do. I do not know how to thank the people who opened doors for me, but I do know how to make sure that the doors are open for the next generation.
Navigating Current Frontline Chemotherapy Options in Pancreatic Cancer
- FOLFIRINOX and NALIRIFOX are commonly used intensive frontline regimens that produce comparable survival outcomes, with a median progression-free survival of approximately 7.3 months and 7.4 months, respectively, in pooled analyses of phase 3 trials.
- Gemcitabine plus nab-paclitaxel remains a standard frontline option and is frequently selected for patients who may not tolerate triplet chemotherapy, although pooled analyses have shown shorter median progression-free survival of approximately 5.7 months compared with triplet regimens.
- Meta-analysis data suggest no statistically significant differences in objective response rates among NALIRIFOX (41.8%), FOLFIRINOX (31.6%), and gemcitabine plus nab-paclitaxel (35.0%), although the regimens have distinct adverse effect patterns that influence regimen selection in clinical practice.
When a patient first presents with metastatic pancreatic cancer, what treatment goals guide the initial therapy discussion?
Approaching [the management of] metastatic pancreatic cancer requires an understanding of the therapeutic options, but also a recognition that patient goals and wishes are important. At the end of the day, treatment for metastatic pancreatic cancer is currently palliative in nature. I always tell my patients the goal is to prolong life as much as possible while giving quality to that life.
Having a conversation with patients about what is important to them, their goals, and milestones they would like to hit is vital. We must also discuss which toxicity profiles are more tolerable to them—physically, emotionally, and psychologically. Additionally, many of our metastatic pancreatic cancer patients are symptomatic, experiencing a decline in performance status, pain, weight loss, or diarrhea. Typically, patients who respond to chemotherapies for pancreatic cancer see symptomatic improvement, but we must balance that against toxicities that can sometimes make those symptoms worse.
How do you handle discussions of prognosis with patients to help them guide them through shared treatment decision-making?
The focus for me is always to emphasize that although this is not something that is curable, it is treatable, and that treatment is focused on the overall improvement of quality of life. We traditionally have 2 essential cocktails or backbones in terms of treatment options, and each offers varying adverse effect profiles.
Assuming the patient wants treatment, most of our patients see all of these different drugs in some form and combination. It is really a question of how they want to start and how aggressive we need to be. For some patients, we need to see cytoreduction—a nice response in the tumor—pretty quickly, and that drives the decision. Other patients have a performance status, or perhaps obstructive jaundice and elevated bilirubin, that precludes certain drugs. I tell my patients that most of the time they get to drive their care. They tell me if they want treatment and how much they want; sometimes I have to make the tough decisions and have tough conversations about what we can and cannot do.
How has your choice to utilize FOLFIRINOX in the first line for metastatic pancreatic cancer changed since the February 2024 FDA approval of NALIRIFOX?1
Thankfully, NALIRIFOX [irinotecan liposome (Onivyde), oxaliplatin, 5-fluorouracil (5-FU), and leucovorin] came at a time after which most of us were already really comfortable with FOLFIRINOX [5-FU, leucovorin, irinotecan, and oxaliplatin], so we understand the drugs. The liposomal irinotecan has some slight tweaks compared to traditional irinotecan, but we know how to give FOLFIRINOX and NALIRIFOX safely and in a tolerable way.
The big thing with the NALIRIFOX component is sometimes worsening diarrhea and a bit more neutropenia. However, when you look at the large studies, the toxicity profile was manageable. It becomes a question of your comfort level as the physician. I still use a lot of FOLFIRINOX, but that doesn’t mean NALIRIFOX is not part of my treatment regimen. For those to whom we do give NALIRIFOX, I haven’t necessarily noticed worse or different outcomes. Many of us use them essentially interchangeably, with the recognition that NALIRIFOX is now approved in the frontline setting and is therefore easier to get authorized.
What patient- or disease-specific factors and toxicity risks influence choosing between FOLFIRINOX and NALIRIFOX, or another first-line option?
I once had a patient remind me that even grade 2 diarrhea is really impactful on quality of life in terms of the number of times they have to run to the bathroom and their ability to leave the house comfortably. For people who already have diarrhea from pancreatic insufficiency or celiac plexus infiltration that leads to rapid transit, I am a little more hesitant to use NALIRIFOX. We can usually mitigate it with preemptive anti-diarrheals, but those are the patients for whom I would lean more toward FOLFIRINOX. Because I have been giving FOLFIRINOX for so long, it ends up being one of my go-to regimens.
Patient preference also factors in regarding the pump. Some patients do not love the pump. Performance status is also key; sometimes 3 drugs are just too hard on patients. In those cases, gemcitabine and nab-paclitaxel [Abraxane] is an option. We can tweak how we give gemcitabine/nab-paclitaxel so that people aren’t always getting it 3 weeks in a row with one week off, which makes it more tolerable. I definitely believe there is still a role for gemcitabine/nab-paclitaxel, but I tend toward a 3-drug regimen unless the patient profile suggests they may have difficulty tolerating it.
What key unmet needs remain in first-line metastatic pancreatic cancer, and where should next-generation strategies build on current chemotherapy options?
The obvious one that everyone has their eyes on are the RAS inhibitors. Approximately 90% of pancreatic cancers have RAS mutations, primarily in KRAS. We are all anxiously awaiting the availability of these drugs in the second-line and beyond, but there are ongoing trials looking at them in the frontline setting.
I have been using the term ‘game changer’ because they have the potential to be the first targeted therapy outside of erlotinib [Tarceva] that we have used in the frontline space. It will be important to look at the cumulative toxicities. RAS inhibitors can cause diarrhea and rash, which can be overlapping with our chemotherapies. I imagine we will see improved efficacy; the question will be the tolerability and how we learn to give these safely so that patients maintain their quality of life. I believe they will eventually be available in the frontline setting, probably in combination with chemotherapy.
When targeted agents and trials are available, how is the decision made between standard first-line chemotherapy and clinical trial enrollment?
I err toward a clinical trial if one is available. I tell my patients all the time that the cures of today were yesterday’s clinical trials. If a trial is scientifically sound and rational, and has phase 1 or phase 2 data to support it, I don’t see why you wouldn’t consider it. In many of these trials, everyone is still getting the chemotherapy backbone, so they aren’t missing out on the standard of care or receiving a placebo in place of treatment.
Using RAS inhibitors as an example, the tricky part is a supply and demand issue. We have many patients with newly diagnosed metastatic pancreatic cancer and limited clinical trial slots. I tell my patients that gemcitabine/nab-paclitaxel or FOLFIRINOX isn’t going anywhere. If there is a frontline treatment trial that makes sense, I would opt for that first and hold onto our traditional cocktails for subsequent lines of treatment.
References
- FDA approves irinotecan liposome for first-line treatment of metastatic pancreatic adenocarcinoma. FDA. February 13, 2024. Accessed March 9, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-irinotecan-liposome-first-line-treatment-metastatic-pancreatic-adenocarcinoma
- Nichetti F, Rota S, Ambrosini P, et al. NALIRIFOX, FOLFIRINOX, and gemcitabine with nab-paclitaxel as first-line chemotherapy for metastatic pancreatic cancer: a systematic review and meta-analysis. JAMA Netw Open. 2024;7(1):e2350756.doi:10.1001/jamanetworkopen.2023.50756
