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Preliminary Data Suggest Neoadjuvant Chemoradiotherapy May Improve Outcomes in Patients With Early Stages of Pancreatic Cancer


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Geertjan van Tienhoven, MD, PhD

Geertjan van Tienhoven, MD, PhD

For patients with newly diagnosed, potentially resectable pancreatic cancer, neoadjuvant chemoradiotherapy led to better outcomes when compared with immediate surgery followed by chemoradiotherapy in the phase III PREOPANC-1 trial. Approximately 25% fewer deaths occurred among patients in the Dutch Pancreatic Cancer Group study treated with the preoperative approach, compared to the standard of care, according to Geertjan van Tienhoven, MD, PhD, of the Academic Medical Center in Amsterdam, who reported the preliminary findings at the 2018 ASCO Annual Meeting.1 

This is the first randomized clinical trial to show that preoperative treatment improves outcomes for people with early stages of pancreatic cancer who can have surgery.
— Geertjan van Tienhoven, MD, PhD

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In a subgroup analysis of patients who underwent resection (R0/R1), the benefit of neoadjuvant treatment was pronounced, with a median overall survival of 42.2 months vs 16.8 months with standard therapy (P < .001). 

“This is the first randomized clinical trial to show that preoperative treatment improves outcomes for people with early stages of pancreatic cancer who can have surgery. We believe this may be a practice-changing trial,” Dr. van Tienhoven commented. 

Many systematic reviews and retrospective analyses have recently found benefit for neoadjuvant therapy. A recent systematic review showed an advantage not only for the patients actually undergoing resection, but also by intention to treat of neoadjuvant therapy over upfront surgery.2 Randomized phase III studies, however, are lacking and are needed to establish benefit, he said. 

PREOPANC-1 Details

The PREOPANC-1 trial enrolled 246 patients with resectable or borderline-resectable pancreatic adenocarcinoma from 16 Dutch institutions. Patients were randomly assigned to immediate surgery, which is the standard of care, or to preoperative chemotherapy plus radiotherapy for 10 weeks, followed by surgery. The neoadjuvant chemoradiotherapy regimen consisted of 15 fractions of radiation at 2.4 Gy plus gemcitabine, preceded and followed by a cycle of gemcitabine alone. Both approaches were followed by adjuvant gemcitabine. 

A trend for improvement in overall survival was shown, with median survival in the intent-to-treat analysis being 17.1 months with neoadjuvant chemotherapy vs 13.7 months with immediate surgery (hazard ratio [HR] = 0.74; P = .074). Median disease-free survival was significantly better, at 9.9 months vs 7.9 months, respectively (HR = 0.71; P = .023), and a number of other secondary endpoints also favored neoadjuvant chemoradiotherapy (Table 1). Although R0 resection rates were higher after neoadjuvant treatment, resection rates overall were not higher.

Safety Profile, Next Steps

The two arms had a similar safety profile, with no higher risk for grade ≥ 3 adverse events with the newer approach. Serious adverse events were reported by 46% of the neoadjuvant arm and 39% of the immediate-surgery arm (P = .28).

PREOPANC-1 TRIAL

  • The phase III PREOPANC-1 trial by the Dutch Pancreatic Cancer Group compared neoadjuvant chemoradiotherapy to immediate surgery, both followed by adjuvant chemotherapy, in 246 patients with newly diagnosed, resectable pancreatic cancer.
  • In this preliminary analysis, the neoadjuvant approach resulted in a trend toward longer overall survival: 17.1 months vs 13.7 month with the standard of care (HR = 0.74, P = .074), in the intention-to-treat population.
  • In a subgroup analysis of patients who underwent a resection (R0/R1), the benefit of neoadjuvant treatment was pronounced, with median overall survival of 42.2 months vs 16.8 months with standard therapy (P < .001).
  • A variety of secondary outcomes were also significantly improved, without an increase in adverse events.

The authors noted the results are preliminary, as only 149 of the required 176 events have occurred, and they acknowledged that perhaps a more effective neoadjuvant regimen may result in even larger differences. FOLFIRINOX or FOLFIRINOX plus stereotactic body radiation therapy have appeared potentially beneficial in other studies and should be tested against neoadjuvant gemcitabine and standard radiotherapy, they suggested. ■

DISCLOSURE: Dr. van Tienhoven reported no conflicts of interest. 

REFERENCES

1. van Tienhoven G, Versteijne E, Suker M, et al: Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1): A randomized, controlled, multicenter phase III trial. 2018 ASCO Annual Meeting. Abstract LBA4002. Presented June 4, 2018. 

2. Versteijne E, Vogel JA, Besselink MG, et al; Dutch Pancreatic Cancer Group: Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. Br J Surg 105:946-958, 2018.


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