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Key Trials Warrant Consideration in Early-Stage Pancreatic Cancer Paradigm

Caroline Seymour
Published: Wednesday, Mar 13, 2019

Dr Nilofer S. Azad
Nilofer S. Azad, M
The incidence of pancreatic cancer is on the rise—a phenomenon that can only be counteracted by better diagnostics and therapeutic strategies, explained Nilofer Saba Azad, MD, an associate professor of oncology at Johns Hopkins Medicine.

If a patient is diagnosed with localized disease, it is termed resectable, borderline resectable, or locally advanced, prefaced Azad in a presentation during the 2019 OncLive® State of the Science Summit™ on Gastrointestinal Cancers.

However, only 20% of pancreatic cancer cases are considered resectable at time of diagnosis. As such, many trials have been conducted to see if there are ways to enhance the resection rates for patients with borderline resectable tumors or to improve responses to chemotherapy and radiation in those who are ineligible for surgery. Moreover, investigators are also examining ways to convert patients with unresectable disease into candidates for resection.

Several trials have examined the use of neoadjuvant chemotherapy and radiation in borderline resectable and locally advanced cancers, said Azad, but as single-center, nonrandomized studies, they have had little impact on the field.

However, data from 3 recent pivotal trials have influenced practice and/or warrant consideration when treating patients with localized disease, said Azad.


Historically, the standard of care for patients with resectable or borderline resectable tumors has been surgery followed by adjuvant chemotherapy. Although prior studies that have suggested the benefit of neoadjuvant therapy have been mainly observational in nature, the data were enough to warrant further exploration, explained Azad.

The phase III PREOPANC-1 trial took patients who were eligible for surgery at the time of enrollment and randomized them to receive surgery upfront and 6 months of adjuvant chemotherapy (n = 127) or neoadjuvant chemoradiotherapy followed by surgery and 4 months of adjuvant chemotherapy (n = 119).

In the experimental arm, patients received 1 cycle of gemcitabine prior to and following 15 fractions of 2.4 Gy radiation therapy in combination with 1000 mg/m2 of gemcitabine on days 1, 8, and 15. Overall survival (OS) served as the primary endpoint among the intent-to-treat population.

Baseline characteristics were well balanced between the 2 arms in terms of age, performance status, and resectability, said Azad.

At the time of data cutoff, 72% (n = 91) of patients in the control arm underwent resection compared with 60% (n = 72) of patients in the experimental arm (P = .065).1 Serious adverse events (AEs) occurred in 39% (n = 49) and 46% (n = 55) of patients in the control and experimental arms, respectively (P = .28). The rate of R0 resection was more than doubled in the experimental arm compared with the control arm (63% [n = 45] vs 31% [n = 28], respectively; P <.001), said Azad.

Although neoadjuvant therapy resulted in a 3.4-month extension in median OS compared with upfront surgery, it failed to demonstrate statistical significance (HR, 0.74; P = .74).

In the subset analysis, investigators noted a benefit with neoadjuvant therapy with regard to the secondary endpoints of metastasis-free survival (MFS; HR, 0.71; P = .013) and the locoregional recurrence-free interval (HR, 0.55; P = .002). Moreover, if patients achieved an R0 resection, they experienced a dramatic improvement in median OS at 42.2 months versus 16.8 months (P <.001).

Now that FOLRINOX has become the optimal regimen in pancreatic cancer, the question of whether or not it can replace gemcitabine in combination with chemoradiation remains unknown, said Azad. Nonetheless, this study provides clinicians with preliminary phase III data to support giving chemoradiation preoperatively.


In 2013, the combination of gemcitabine and nab-paclitaxel (Abraxane) showed a survival benefit compared with single-agent gemcitabine in patients with advanced disease. As such, the nonrandomized phase II LAPACT trial2 was designed to assess the safety and efficacy of 6 cycles of induction therapy with the combination in patients with locally advanced treatment-naïve disease.

In the induction phase of the trial, 106 patients received 125 mg/m2 of nab-paclitaxel in combination with 1000 mg/m2 of gemcitabine days 1, 8, and 15 of each 28-day cycle for up to 6 cycles, after which patients were able to continue on the prespecified treatment, begin chemoradiation, or undergo surgical resection, if eligible. Of the 61 patients who completed induction therapy, 45 went on to receive investigator’s choice of nab-paclitaxel/gemcitabine (n = 12), chemoradiation (n = 17), or surgery (n = 16).

“No matter which approach you take, you have preserved quality of life (QoL),” said Azad.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Medical Crossfire®: Navigating Treatment Decisions in Pancreatic Cancer: Key QuestionsJun 29, 20191.5
Community Practice Connections™: 2nd Annual International Congress on Oncology Pathology™Aug 31, 20191.5
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