Outcomes remain poor in locally advanced pancreatic cancer

1. Compared to induction chemotherapy alone, maintenance chemoradiotherapy did not prolong overall survival or time to disease progression in patients with locally advanced pancreatic cancer.

2. Chemoradiotherapy was able to reduce the rate of local disease progression and was not associated with an increase in significant toxicity.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Pancreatic cancer accounts for less than 3% of all cancer diagnoses in the United States. However, it typically presents late, follows an aggressive course, and is notoriously difficult to treat, making it one of the leading causes of cancer death nationwide. Patients with locally advanced disease (stage III) are not candidates for surgical treatment, and optimal treatment regimens have remained a topic of debate. Prior studies disagreed about the utility of radiation, and suggested that outcomes may be affected by induction chemotherapy. Thus, this study aimed to compare the results of chemotherapy alone versus chemoradiotherapy in patients with locally advanced disease, after receiving induction chemotherapy.

Overall, the study found no difference in overall survival when comparing maintenance chemotherapy and chemoradiotherapy. Moreover, the study was stopped early after both treatment regimens were found to be futile, with 94% of all patients dying within 33 months of follow-up. While this study enrolled a large number of patients from many different sites, it was limited by its use of a non-optimized chemotherapy regimen, as FOLFIRINOX has replaced largely gemcitabine. However, this result reiterates the fact that more efficient systemic treatments are needed in the treatment of locally advanced chemotherapy.

Click to read the study in JAMA

Relevant Reading: Pancreatic Cancer

In-Depth [randomized clinical trial]: The LAP07 trial was an open-label, unblended, phase III, randomized controlled trial that was conducted between 2008 and 2011. Patients with confirmed stage III pancreatic cancer were enrolled into the study and initially randomized to receive induction chemotherapy with gemcitabine alone or gemcitabine plus erlotinib. After 4 months of therapy, patients were assessed for tumor response. In those who were “controlled” on induction chemotherapy (those with stable disease or an objective response), a second randomization was performed; half of the patients received maintenance chemotherapy with the same regimen and the other half received capecitabine plus radiation.

Of the 449 patients initially enrolled in the study, only 269 underwent the second randomization. The study was closed early after both maintenance therapy regimens appeared futile. Two-hundred and twenty-one patients died with a median follow-up of 36.7 months. The overall survival was similar between the groups (chemotherapy OS 16.5 months, 95%CI 14.5-18.5 months; chemoradiotherapy OS 15.2 months, 95%CI 13.9-17.3 months; HR 1.03, p = 0.83). Likewise the overall survival was similar among patients receiving gemcitabine or gemcitabine plus erlotinib. While 88% of patients had disease progression while on the study, chemoradiotherapy was associated with lower rates of local disease progression (p = 0.04) and similar rates of grade III and IV toxicity (with the exception of nausea, p = 0.008) when compared to chemotherapy alone.

Image: PD

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