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, CancerNetwork® spoke with Kelly A. Rone, DNP, RN, AGNP-c, about the current state of pancreatic cancer, emphasizing risk factors, diagnostic challenges, and treatment planning. Rone is an advanced practice nurse of gastrointestinal oncology at Mayo Clinic in Phoenix, Arizona.

Rone initially discussed patient counseling for risk factors, making a distinction between modifiable risk factors—such as smoking, drinking, and obesity—and nonmodifiable risk factors, which primarily include genetic syndromes. Rone then highlighted a need for more effective screening methods, highlighting a lack of screening tools that have been proven to be highly effective, as well as the tendency for pancreatic cancer to be identified at a later stage.

Rone then touched upon treatment-emergent adverse effects (AEs), as well as how her practice manages them. She particularly placed emphasis on appetite loss, which may prove difficult for patients attempting to recover from cancer treatment. Additionally, Rone suggested various methods to encourage food consumption in spite of appetite loss.

Rone expressed that she connects patients with pancreatic cancer to palliative care frequently, explaining that patients can benefit from involvement in terms of managing AEs and extending life expectancy. Furthermore, she stressed a need to correct misconceptions of palliative care as exclusively entailing pre-hospice care, highlighting benefit in all patients regardless of disease stage.

Rone iterated that addressing psychosocial needs for patients varies depending on a patient’s circumstances. Rone then suggested that viewing patients as individuals with lives beyond their cancer diagnosis can help humanize them and can help to foster more meaningful discussions regarding cancer treatment than electronic health records alone.

Then, Rone expressed a desire to find ways to detect pancreatic cancers sooner by developing biomarkers, highlighting how pancreatic cancer may be paired with several vague symptoms that make early detection difficult. Rone explained that early detection of pancreatic cancers can be associated with better outcomes.

She further expressed a need to elicit better treatment outcomes for pancreatic cancer based on low responsiveness to chemotherapy. Rone concluded by emphasizing a need for education regarding 2 distinct types of pancreatic cancer––pancreatic adenocarcinoma and pancreatic neuroendocrine cancer––to better manage patient expectations.

Pancreatic Cancer Awareness Month

A nurse practitioner discussed risk factors, diagnostic challenges, and treatment planning in patients with pancreatic cancers.

Managing Risks, Planning Treatment, & Making Progress in Pancreatic Cancer 

 Tanios S. Bekaii-Saab, MD, spoke about various developments in the pancreatic cancer treatment field. Throughout the discussion, Bekaii-Saab weighed the benefits of currently available chemotherapeutic regimens for patients with metastatic disease, discussed research on the potential for precision medicine in those with 

wildtype pancreatic ductal adenocarcinoma (PDAC), and detailed ongoing initiatives to improve outcomes among those with 

mutations and other targetable genomic alterations.

Bekaii-Saab is the David F. and Margaret T. Grohne Professor of Novel Therapeutics for Cancer Research, chair and consultant in the Division of Hematology and Medical Oncology at Mayo Clinic in Arizona, and co-leader of Advanced Clinical and Translational Science at Mayo Clinic Cancer Center.

mutations and other alterations in patients with pancreatic cancer, Bekaii-Saab especially emphasized the use of genomic analysis to inform personalized treatment decision-making in the field. Screening patients to detect aberrations such as microsatellite instability-high tumors, 

fusions can open the door for the development and use of targeted agents, which may consequently improve patient outcomes.

Looking ahead, Bekaii-Saab noted the need to adapt the therapies that have shown activity in the later stages of the disease to earlier treatment settings. Although “great work” has been achieved with chemotherapy and surgical techniques, he highlighted the importance of bringing targeted agents to earlier lines of therapy to further increase the likelihood of positive outcomes for patients.

“I have never been more optimistic. I’m always the eternal optimist, but I’m even more optimistic today that we’re going to move the needle for our patients with pancreatic cancer and continue to enhance that likelihood of living longer, having a better quality of life, or even increasing the level of a cure for this cancer,” Bekaii-Sabb stated. “Certainly, the future looks bright. We’re chipping away, one drug at a time. We can now remove that whole concept of nihilism in pancreatic cancer and look quite optimistically on the future.”

Tanios S. Bekaii-Saab, MD, provides an overview of current therapy options and ongoing initiatives involving targetable alterations in those with pancreatic cancer.

Advancing Research and Targeting Genomic Alterations in Pancreatic Cancer

 spoke with Kamran Idrees, MD, MSCI, MMHC, FACS; Natalie A. Lockney, MD; and Milad Baradaran, PhD, DABR, about the potential utility of intraoperative radiation therapy (IORT) among patients with pancreatic cancer. The group detailed the design and mechanism, gradual technical advancements, and trial data supporting the application of this radiotherapy modality for this patient population.

Idrees is the chief in the Division of Surgical Oncology & Endocrine Surgery, an associate professor of surgery, an Ingram Associate Professor of Cancer Research, and director of Pancreatic and Gastro-Intestinal Surgical Oncology at Vanderbilt University Medical Center. Lockney is an assistant professor in radiation oncology and the program director for the radiation oncology medical residency at Vanderbilt University Medical Center. Baradaran is the head of quality assurance operations and assistant professor in the Department of Radiation Oncology at Vanderbilt University Medical Center.

As part of this discussion revolving around IORT, the group outlined the optimal conditions for using this technique depending on the extent of disease resectability in patients. Specifically, Idrees categorized patients as belonging to one of 3 major groups: those with metastatic disease, those with resectable disease, and those with borderline resectable or locally advanced disease. When considering these factors, patients with borderline resectable disease may be suitable to undergo IORT in combination with chemotherapy, radiotherapy, and surgery.

The conversation also focused on a particular case involving a patient with pancreatic cancer who received IORT at their institution. Based on the outcome of this case, they highlighted how multidisciplinary collaboration in combination with careful patient selection may offer surgical resection through IORT.

“[There] has to be a multidisciplinary team approach to carefully select these patients and [determine] who can benefit from this procedure,” Idrees said. “For the families and the physicians who are taking care of [patients with] pancreatic cancer, it’s valuable to obtain a second opinion, even if [the tumor is] initially deemed unresectable. What’s unresectable in one surgeon’s hands may be resectable in a different team,” he added.

Experts from Vanderbilt Medical Center review mechanisms, supporting data, and patient cases associated with the use of IORT in pancreatic cancer.

Advancing Pancreatic Cancer Care Through Intraoperative Radiation Therapy

Starting April 1, 2024, Diane M. Simeone, MD will start her new position as director of the University of California San Diego (UCSD) Health Moores Cancer Center.

, Simeone highlighted her excitement to be working with an institution that she said aligns with her goals and values. During her time as director, she said that she wants to focus more on early detection of pancreatic cancer, which may help save many patients. Additionally, some of her short- and long-term goals include submitting a Cancer Center Support Grant to the National Institutes of Health and expanding clinical trial efforts at UCSD. She also discussed ongoing projects she will aim to work on, such as the UC Pancreatic Cancer (UCPCC) Consortium and the Pancreatic Cancer Early Detection (PRECEDE) Consortium.

Prior to beginning her new position at UCSD, Simeone has been the Laura and Isaac Perlmutter Professor of Surgery, director of the Pancreatic Cancer Center, and the associate director of translational research at Perlmutter Cancer Center at New York University Langone Health. Additionally, she was previously the chair of the scientific and medical advisory board of the Pancreatic Cancer Action Network and a member of the scientific advisory board for the Let’s Win Pancreatic Cancer online community.

“It was clear that everybody is aligned with this mission and understands the importance of how we care for patients with cancer and do research at the cancer center,” Simeone said during the interview. “There seems to be a clear commonality of thinking on their vision of being at the forefront of advancing science and, most importantly, how we apply to take care of patients. Patients are always the driving force. That's always the center of what we need to be thinking about.”

World-renowned surgeon named new director of Moores Cancer Center at UC San Diego Health. News release. University of California San Diego. January 8, 2024. Accessed January 25, 2024. http://tinyurl.com/4986f4cb

UC Pancreatic Cancer Consortium. University of California Health. Accessed January 25, 2024. http://tinyurl.com/3szdvyxv

PanCAN’s Precision Promise adaptive clinical trial platform –. Pancreatic Cancer Action Network. Published April 27, 2016. Accessed January 25, 2024. http://tinyurl.com/fpax5hhd

Diane M. Simeone, MD highlights the importance of multidisciplinary care, surgical practices, and early detection in pancreatic cancer care. 

Diane M. Simeone, MD “Thrilled” To Be UCSD Moores Cancer Center Director

 spoke with Christine Chung, DO, of the Swedish Medical Center in Englewood, Colorado, about “

Characterization of Blood-Based Molecular Profiling in Pancreatic Adenocarcinoma

,” a retrospective review published in the journal 

Chung detailed this research, which characterizes the mutational landscape of patients with metastatic pancreatic adenocarcinoma who received blood-based molecular profiling. A total of 77 consecutive patients were included in the analysis. She also spoke about pancreatic adenocarcinoma, the study’s main findings, and how this research can inform future treatment decision making moving forward.

Don’t forget to subscribe to the “Oncology Peer Review On-The-Go” podcast on Apple Podcasts, Spotify, or anywhere podcasts are available.

Christine Chung, DO, spoke with CancerNetwork® about the latest research from the journal ONCOLOGY® about implications of blood-based molecular markers in pancreatic adenocarcinoma.

Oncology Peer Review On-The-Go: Characterization of Blood-Based Molecular Profiling in Pancreatic Adenocarcinoma

In this week’s “Oncology Peer Review On-The-Go,” we discuss an article from the May issue of the journal 

Molecular Profiling Practices in Pancreatic Adenocarcinoma: Academic vs Community Physicians

. CancerNetwork® spoke with Christine Chung, DO, from the HCA Swedish Medical Center in Englewood, Colorado, about the molecular profiling patterns she and her colleagues observed in this retrospective review. The authors found that both academic and community physicians ordered profiling about 50% of the time, which was contrary to previous reports that suggest academic centers perform molecular profiling more often.

The perspective for this article comes from Roman Groisberg, MD, a medical oncologist and director of the Sarcoma Medical Oncology Program at the Rutgers Cancer Institute in New Brunswick, New Jersey. Groisberg discussed the role of profiling in pancreatic adenocarcinoma, his thoughts on the retrospective review, and the future of profiling for this cohort of patients.

CancerNetwork® dissects an article from the journal ONCOLOGY® focusing on academic and community molecular profiling practices for patients with pancreatic adenocarcinoma.

Oncology Peer Review On-The-Go: Molecular Profiling Practices in Pancreatic Adenocarcinoma

This episode of "Oncology Peer Review On-The-Go" examines an article published in the October issue of the journal 

, titled “Barriers to Clinical Trial Enrollment in Patients With Pancreatic Adenocarcinoma Who Are Eligible for Early-Phase Clinical Trials.”

The piece was written by Rachael Galvin, DO, MPH, Christine Chung, DO, Ella Achenbach, Oliwier Dziadkowiec, PhD, and Shiraj Sen, MD, PhD, and focuses on what keeps patients with this aggressive form of pancreatic cancer from pursuing enrollment in clinical trials. For a summary of the article, 

 spoke with Galvin, lead author of the study who is from the Swedish Medical Center in Englewood, Colorado.

For the article’s response perspective, 

 spoke with Michael Lee, MD, from The University of Texas MD Anderson Cancer Center in Houston. Lee discussed his perspective piece published on 

 titled “Barriers to Pancreatic Cancer Clinical Trials Enrollment.” The piece examines Galvin’s work and clinical trial enrollment for the disease as a whole.

Don’t forget to subscribe to the "Oncology Peer Review On-The-Go" podcast on Apple Podcasts, Spotify or anywhere podcasts are available.

The latest installment of “Oncology Peer Review On-The-Go” dissects original research published in the journal ONCOLOGY regarding potential barriers to clinical trial enrollment for patients with pancreatic cancer.

Oncology Peer Review On-The-Go: Barriers to Pancreatic Cancer Clinical Trial Enrollment

As part of our coverage of the 2018 Gastrointestinal Cancers Symposium, held January 18–20 in San Francisco, we are speaking with Kyaw L. Aung, MBBS, PhD, a clinical fellow at the Princess Margaret Cancer Centre in Toronto. Dr. Aung presented updated data from the COMPASS trial (

), which used whole-genome sequencing and RNA sequencing to analyze the tumors of patients with advanced pancreatic ductal adenocarcinoma to identify possible first-line treatments.

First, can you tell us about the design of the COMPASS study? What is unique about the study, either as a pancreatic cancer study or as a cancer trial in general? 

The COMPASS study was designed to acquire a fresh tumor biopsy from patients with advanced pancreatic cancer, and both locally advanced and metastatic patients were included in this trial. Before starting first-line chemotherapy with either modified FOLFIRINOX or gemcitabine and nab-paclitaxel, we performed whole-genome sequencing and RNA sequencing, prospectively. The study’s aim was mainly to acquire the whole-genome sequencing data 8 weeks from the time of tumor biopsy, so that that information can be used to influence patient management. One of the main secondary endpoints was to identify subsets of patients with unique genomic features who may benefit from personalized- or precision-medicine approaches.

Our study is unique in a few ways. The first thing is that most of the genomic sequencing studies in pancreatic cancer were done in early-stage, resectable cancer. Currently, data is very much limited for advanced-stage pancreatic cancer, mainly because it is very difficult to do molecular profiling studies in advanced disease. It is not easy to get good quality tumor material for whole-genome, RNA sequencing, or other comprehensive molecular profiling types of studies. So this was the challenge we really wanted to overcome. As you can see from other studies, most of the clinical data with large-scale genomic sequencing are retrospective and ours is a prospective trial-and with full clinical annotation-which is very powerful and vey much unique to COMPASS. We really are proud to achieve this in this study.

What were the key results you presented from this update of the trial at the meeting?

So the primary objective of the study was to prove the feasibility-to show that it is possible to do this comprehensive molecular profiling prospectively, and in real time, in the pancreatic cancer clinic. We demonstrated this and the results are impressive. In 98% of the patients that we biopsied, whole-genomic sequencing was successful; in 95% of the patients, RNA sequencing was successful; and I think we achieved this result by team science. One of the features of the study was that we performed laser capture microdissection for tumor content enrichment, and that made a significant difference in getting good quality genomic results.

The main interesting result is the RNA sequencing identified two patient subtypes in pancreatic cancer, classical and basal-like, and we found that the classical subtype responded better to chemotherapy-this is the first prospective evidence that showed difference in response to chemotherapy in pancreatic cancer based on RNA subtype. Also, whole-genome sequencing identified a small subset of patients with unstable genomes, and they responded very well to modified FOLFIRINOX. The interesting thing is that these three patients did not have any germline mutations, so if we had not done whole-genome sequencing we might not have identified this subset, and we are quite excited to see these results.

A third important finding is that about 25% of the patients have genomic alterations that could be targeted with currently available drugs. A cautionary note on this though, whether targeting these genomic aberrations by using currently available drugs will make any difference in terms of clinical efficacy in pancreatic cancer remains very much unknown right now-we still need to do a lot more studies.

What’s next for this trial? Are you recruiting more patients or doing more analyses and follow-up on these current patients?

As you know, these are our preliminary results that were presented at the meeting. Currently, the COMPASS study is still ongoing and we would like to recruit 180 patients as an exploratory dataset. We already recruited more than 100 patients, and we are hoping we will meet the target of 180 patients early next year or the middle of next year at the latest. We really want to update the data and consolidate our findings.

An important thing is that we are now trying to dig deeper to understand the biological mechanism behind these pancreatic ductal adenocarcinoma subtypes and by doing so, we really want to find subtype-specific therapies. I think rather than just subtyping superficially, we really need to understand the underlying biological mechanisms at play in these subtypes. We are working very hard on this and hopefully, with data from all 180 patients, we will be able to present a lot more than what is in these preliminary results.

You mentioned that the trial met your expectations, at least in part, as you were able to obtain whole-genome sequencing data and RNA sequencing data from patients’ biopsies. Were there other expectations going into this trial for you and your colleagues, and how did that compare with the execution of the patient-sample analyses and findings? And what are the implications for doing these types of trials that rely on patients’ tumor-sequencing information?

Our expectation initially was that we would get the data in 80% of the patients that we biopsied, and we exceeded that expectation. Almost all patients could get their genomic data. In terms of the enrollment and patient-sample analysis, we are very pleased with the results. In terms of the findings of possible new therapies for pancreatic cancer based on the genomic results, I have to admit that we still need to do a lot more. We are still just scratching the surface and trying to find the biological mechanisms so that we could target them and also develop new therapies. I think our results definitely established that there are patients with unique subtypes that may benefit from personalized treatment and strategies. And these results need to be validated, which we will continue to do.

I think the implications of this study, in terms of using the genomic sequencing information, is very significant. As you probably know, the findings in most preclinical studies cannot really be translated into the clinic, so what we are focusing on is to translate genomic information into the pancreatic cancer clinic to have an impact on patient management. Obviously this is challenging, and we are at the very beginning, but we really believe that we are on the right track. The major impact of these kinds of studies and trials will be to change the treatment paradigm in advanced pancreatic cancer and finally to improve patient survival outcomes. We really believe that we can achieve that by using patients’ tumor sequencing information.

Thank you so much for joining us today, Dr. Aung.

In this interview we discuss preliminary results of the COMPASS trial, which used whole-genome sequencing and RNA sequencing to analyze the tumors of patients with advanced pancreatic ductal adenocarcinoma to identify possible first-line treatments.

COMPASS: Genomic Profiling Could Guide Treatment in Advanced Pancreatic Cancer

Today we are discussing pancreatic cancer, the most deadly cancer in the United States. According to the National Cancer Institute, the 5-year survival rate is about 6%, mostly due to the high rate of first diagnosis once the cancer has already metastasized-about 53% of all cases are diagnosed once the cancer has spread to other organs. The 5-year survival rate for local or regional pancreatic cancer is about 24%, but unfortunately this type of cancer is usually detected after the tumor has metastasized. Approximately 45,000 people were diagnosed with pancreatic cancer in 2013 and almost 38,500 died of the disease. It is the 12th most common cancer in the United States and the 4th most common cause of cancer deaths. According to the annual reports on cancer by the National Cancer Institute and the American Cancer Society that were recently issued, both pancreatic cancer incidence and death rates have increased in the last 10 years.

Pancreatic cancer remains difficult to treat. We are speaking with Eileen O’Reilly, MD, a medical oncologist and pancreatic cancer expert at Memorial Sloan-Kettering Cancer Center in New York City, where she treats patients and develops novel therapies for patients with different stages of the disease.

Dr. O’Reilly, could you briefly describe the current neoadjuvant and adjuvant therapies used to treat pancreatic cancer?

Dr. O’Reilly:  For the majority of people who undergo surgery, undertaken with a potentially curative intent, adjuvant therapy is the main consideration. An international standard at the current time is single-agent gemcitabine given for 6 months, which has been shown to decrease the risk of relapse and to enhance overall survival. Some institutions take an approach of offering neoadjuvant or preoperative therapy for those with resectable pancreatic cancer, with the goals of trying to affect the delivery of systemic therapy sooner rather than later and to get more modalities of treatment into more patients, hoping that that will impact longer-term outcomes. It is fair to say that neoadjuvant therapies are conducted in select centers, and there have been no randomized trials comparing preoperative with postoperative therapy to know which may be a superior approach. Having said that, I think with developments in treatments for metastatic disease and the advent of more effective systemic therapies, it is clear that there has been a resurgent interest in neoadjuvant therapy to integrate some of these newer, more active therapies into preoperative treatment. There is much more to come on this topic.

Are there any major trials ongoing now in these two settings, either neoadjuvant or adjuvant, that you would like to highlight?

Dr. O’Reilly: Sure. Regarding adjuvant therapy, does adding a second agent to gemcitabine improve overall survival? In Europe, capecitabine is being added to gemcitabine and being compared with gemcitabine alone in the European Study Group for Pancreatic Cancer (ESPAC)-4 trial, which is substantially accrued at this point. But the data will need to mature for a number of years before there is a definitive answer. In North America, the current ongoing national study is the RTOG 0848 trial. This study is a twofold trial that is looking at the addition of erlotinib (the oral tyrosine kinase inhibitor) to gemcitabine, and then second randomization to plus or minus fluoropyrimidine-based radiation. The study is actually being amended as we speak to remove erlotinib, as the signal from a locally advanced European study does not suggest a strong, or any, advantage from the addition of erlotinib in this setting. The trial as it stands will go on to complete recruitment with gemcitabine as the backbone followed by a randomization to chemoradiation.

In Japan, the Japan Adjuvant Study Group of Pancreatic Cancer (JASPAC)-01 study has been recently reported and suggests that S-1, another oral fluoropyrimidine, had in a Japanese patient population not only met a non-inferiority design compared with gemcitabine but actually looked to be superior to gemcitabine in the adjuvant setting. Mature data are still awaited on this, but this is certainly interesting. What this means for a North American and Western population is unclear. Other studies in the United States with S-1 haven’t suggested the ability to administer the same dose of S-1 nor the same signals seen in the Asian population. Other considerations that could be at play include diet and pharmacogenomic differences in different patient populations.

With regard to neoadjuvant therapy, the first North American multicenter trial has completed recruitment by the American College of Surgeons Oncology Group and those data are maturing. In Europe, the first study comparing neoadjuvant with adjuvant treatment looking at gemcitabine and oxaliplatin, is underway. Those are the highlights, and I’ll mention one last adjuvant trial for which we don’t have data yet but has completed recruitments (and it's a different tack altogether). It's incorporating the drug algenpantucel-L, which is a form of immune therapy in the adjuvant setting based on a smaller phase II study, which provided an interesting signal. This is using transplant rejection hyperacute immunity to enhance survival. Those data are also maturing, and we will hopefully have results, if not by the end of 2014, then a bit later than that.

The last therapy approved for advanced pancreatic cancer by the US Food and Drug Administration (FDA), this past September [2013], was Abraxane, which is an injection of paclitaxel chemotherapy bound to albumin. Can you talk about how you use Abraxane, and what are the other current therapy options for metastatic disease?

Dr. O’Reilly: Albumin-bound paclitaxel, which is also called nab-paclitaxel, was recently approved in combination with gemcitabine for front-line treatment of metastatic pancreatic adenocarcinoma in patients with a relatively good performance status. This particular combination, in comparison with gemcitabine, showed an improvement in tumor response, disease control, and overall survival. In addition, it provides a backbone for adding new novel agents. Gemcitabine and now paclitaxel are becoming integrated as standard options in the front-line setting in pancreatic adenocarcinoma.

The other main option for good performance status patients, which is not FDA-approved because of the nature of how the study was designed, is the combination called FOLFIRINOX, which consists of oxaliplatin, leucovorin calcium, fluorouracil, and irinotecan. Similarly to gemcitabine and paclitaxel, it showed improved tumor control and overall survival benefit over gemcitabine alone. These two options, FOLFIRINOX and gemcitabine plus nab-paclitaxel, have not been compared head-to-head, and the way we think about it is that for the first time in the treatment of metastatic pancreatic cancer, we now have the luxury of some choices. Both of these options are aimed at the higher end of the performance status of the patient population, particularly for FOLFIRINOX. The data from that trial were conducted in patients with an Eastern Cooperative Oncology Group (ECOG) 0 or 1 Performance Status compared with the broader population of the nab-paclitaxel/gemcitabine study.

Many clinical trials are building on gemcitabine and nab-paclitaxel, as this is probably going to be an easier platform to build upon compared with FOLFIRINOX, given the relative intensity and toxicity profile of FOLFIRINOX. Having said that, my personal bias for people with an excellent performance status, outside of a study setting, based on the comparison of the data (which is fraught with limitations in terms of the nuances of the trial design), is in favor of FOLFIRINOX.

What about immunotherapies? Is there evidence that pancreatic cancer could be amenable to some of the newer immunotherapy antibodies or T-cell immunotherapies that are in development?

Dr. O’Reilly: The question of immunotherapy for pancreatic cancer is certainly an emerging one. I mentioned algenpantucel-L as being studied in the adjuvant setting and now also in locally advanced pancreatic cancer. There certainly is the hope that based on data from anti–PD-1, anti–PD-L1, and anti–CTLA-4 agents in other malignancies that would not be considered strongly immunogenic (such as lung cancer and renal cancer, where signals have been seen), that that may translate to a broader range of solid tumor malignancies that can be treated. There is limited data yet with checkpoint inhibitors in pancreatic cancer, but studies are underway evaluating both PD-L1 and PD-1 antibodies and anti–CTLA-4 therapies, both as single agents and in combination, so there is certainly hope that in the next 6 months we will have more data accrued to know whether this is an avenue worthy of continued development.

A couple other immune therapy approaches to mention are relatively early in development. One is the adoption of a CAR, or chimeric antigen receptor, approach targeting mesothelin. The first studies are underway in a select group of patients to see if this approach may have utility in solid tumors and particularly in pancreatic cancer. And in metastatic disease, a small randomized phase II trial of a 

 vaccine, CRS-207, combined with GVAX, a vaccine developed at Johns Hopkins for an extended period of time has shown an interesting signal in refractory pancreatic cancer patients. A larger randomized phase II study has been designed to evaluate the robustness of that early signal. These approaches are very interesting, and I think the field is keeping a close watch on what is happening in this field for pancreatic cancer.

Have there been advances you can highlight in identifying pancreatic cancer targets? Are there any targeted agents that are still preclinical or are now starting to be tested in early-stage trials that you can discuss?

Dr. O’Reilly: The area of targeted treatment in pancreatic cancer is one that has had a long tradition but not one with a huge amount of success. There is actually one approved targeted treatment, erlotinib, but the clinical significance and the value of that has been hotly debated in the field-having said that, an area that has been emphasized is the whole tumor microenvironment, as well as the interaction of the tumor and the stroma, and the coexistence of the two in pancreas cancer. A number of ongoing and recent approaches have targeted this area in pancreatic cancer. For example, some of the immune therapies that we touched on, that’s partly how some of those agents are thought to work, by targeting the microenvironment.

But other approaches include pegylated PH20, which is a hyaluronidase, a degradation agent that has shown some activity, both preclinically and in an early phase Ib trial, and is now being tested in combination with gemcitabine and nab-paclitaxel, and will also be looked at in combination with FOLFIRINOX. That is an interesting area for which there is potential promise. Another area of research is Hedgehog inhibition. Despite some strong preclinical rationale and support, the translation of that area of targeting to the clinic has been disappointing. A series of randomized phase II trials have matured, and have not shown utility and have even suggested that there may be a negative impact. That research is going back to the preclinical setting to better understand what's been observed clinically.

One area that we are really interested in are the patients with 

 mutations, which are present in a small subset of people with pancreatic cancer, where there may be susceptibility to DNA-damaging agents and where PARP inhibitors are being experimentally implemented. That is probably about 5% to 7% of pancreatic cancers, but certainly in that subgroup, a possibility of more directed tumor-targeting. A very small number of pancreatic cancer patients will have 

 mutations, where known agents for those molecular targets are available and may have potential value.

Thank you so much for joining us today, Dr. O’Reilly.

Dr. O’Reilly: You are very welcome. Thank you.

In this interview, we discuss the current state of pancreatic cancer management, and look toward trials to further define the best course of treatment for this deadly disease. 

Pancreatic Cancer

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